Volume 94  ·   Issue 26  ·  2014

The latest global cancer surveillance report shows that breast cancer is one of the most common malignant tumors in women^[1]。 With the continuous deepening of research, modern breast cancer treatment has entered the era of classification treatment based on molecular typing. Following the guidelines for rational treatment of patients in different stages and categories is also the advantage of individualized oncology medicine. In the treatment of breast cancer, chemotherapy plays an important role in both the early stage of the disease and the stage of recurrence and metastasis. In clinical practice, appropriate regimens and standard doses should be selected to provide optimal treatment for patients.

To explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in monitoring therapy responses and analyze the predictive value of tumor biomarkers in neoadjuvant chemotherapy for breast cancer.

From August 2010 to August 2013, the patients diagnosed as primary invasive breast cancer were admitted into this multi-center study.All of them received 6 cycles of neoadjuvant chemotherapy and DCE-MRI during the procedure and underwent surgery.The associations between clinical therapy response and pathologic response as well as predictive factors were analyzed.

As for evaluating neoadjuvant treatment response, DCE-MRI had statistically significant correlations with histopathology.PR negativity, HER-2 over-expression and high Ki-67 index were statistically correlated with pathologic complete response (pCR) (P<0.05).

DCE-MRI is a reliable method of assessing the response of neoadjuvant therapy for breast cancer.And the immunohistochemistry status of PR, HER-2 and Ki-67 were related with pCR.

To establish human umbilical cord mesenchymal stem cells (HUMSCs) strain transfected with interleukin-18 (IL-18) gene and examine its effects on the proliferation of breast cancer cell (MCF-7).

HUMSCs were isolated and cultured.And the lentivirus-IL-18 vector containing human IL-18 gene was constructed and transfected into HUMSCs.The expressions of IL-18 gene mRNA and protein were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.After co-culturing for 1, 3, 5 days, Transwell and cell counting kit-8(CCK-8)assays were performed on MCF-7 to plot the cell growth curve.

IL-18-HUMSCs could stably express of IL-18 gene and inhibit the proliferation of breast cancer cells.The IL-18 mRNA relative expression amounts were 1.40±0.21 for experimental group (IL-18-HUMSCs), 0.59±0.09 for negative control group (NV-HUMSCs) and 0.71±0.05 for blank control group (HUMSCs). As compared with control group, the difference was statistically significant(F=31.81, P=0.001). The relative expressions of IL-18 protein were 1.54±0.27 for experimental group (IL-18-HUMSCs), 0.57±0.04 for negative control group (NV-HUMSCs) and 0.59±0.23 for blank control group (HUMSCs). As compared with control group, the difference was statistically significant(F=22.32, P=0.002). After co-culturing for 5 days, the cellular proliferation was significantly inhibited.

IL-18 gene has been successfully transfected into HUMSCs and has a stable expression.And IL-18-HUMSCs can effectively inhibit the proliferation of breast cancer cells in vitro.

To examine the expression and prognostic value of novel oncogene Emi1 in breast cancer.

Immunohistochemical analysis was performed for 93 human breast carcinoma samples and adjacent normal tissues for detecting the expression of Emi1 and cell proliferative factor Ki-67. Then the data were correlated with clinicopathological features.

Emi1 was highly expressed in breast carcinoma tissues compared with adjacent normal tissues. Emi1 expression was significantly associated with histological grade(P=0.002), axillary lymph node status (P=0.017) and ER status (P=0.038). However, there was no correlation between Emi1 expression and other factors such as age, tumor size, histology, PR status, HER-2 or P53. Meanwhile similar results were obtained for Ki-67 expression. A marked correlation also existed between Emi1 and Ki-67 expression (Spearman'sr²=0.454, P=0.002).

As a novel breast cancer associated gene, Emil plays an important role in evaluating invasion and metastatic potentiality in breast cancer. And it is also an important prognostic predictor of breast cancer so as to become a potential therapeutic target for breast cancer.

To explore the expression levels and roles of Krüpple-like factor 5 (KLF5) in tumor necrosis factor α (TNFα)-induced SK-BR-3 breast cancer cells.

SK-BR-3 breast cancer cells were stimulated by TNFα at different concentrations (0, 1, 5, 10, 20 μg/L) for specified durations (0, 6, 12, 24, 36 h). Western blot was performed to detect KLF5 protein levels. Then Western blot and quantitative real-time PCR (qRT-PCR) were used to detect the expression levels of apoptosis genes. Flow cytometry and qRT-PCR were used to observe the effects of exogenous KLF5 on TNFα-induced apoptosis of SK-BR-3 breast cancer cell.

KLF5 expression levels significantly decreased in TNFα-stimulated SK-BR-3 breast cancer cells in a concentration- and time-dependent manner. Quantitative RT-PCR results showed that TNFα up-regulate apoptosis gene caspase 3, caspase 9 and bax expression levels and down-regulate bcl-1 level in SK-BR-3 cells. Adenovirus expression vectors of pAd-GFP and pAd-GFP-KLF5 were constructed and used to infect SK-BR-3 breast cancer cells. Over-expression of GFP-KLF5 inhibited apoptosis in TNFα-stimulated SK-BR-3 breast cancer cells.

TNFα reduces KLF5 expression in SK-BR-3 breast cancer cells and KLF5 participates in TNFα-induced SK-BR-3 cell apoptosis.

To explore the clinical characteristics and outcomes of lung cancer patients with venous thromboembolism (VTE).

The clinical data of 80 lung cancer patients with VTE hospitalized from January 2003 to April 2013 at our hospital were reviewed.The clinical factors of age, gender, clinical manifestations, pathological type, clinical stage, performance status and therapeutic regimen were recorded and analyzed. And the pulmonary thromboembolism (PTE) patients with deep venous thrombosis (DVT) were enrolled into PTE group. The occurrences, clinical manifestations and prognosis of VTE were evaluated.

A total of 80 patients were enrolled. There were 40 males and 40 females with a mean age of (65.8±11.3) years. Adenocarcimoma was identified in 58 (72.5%) patients and advanced lung cancer in 71 (88.8%) patients. Among 37 (46.3%) patients with histodifferentiation results, 89.2% (33/37) of them were moderately and/or poorly differentiated. In 32 (40.0%) patients on chemotherapy, 71.9% (23/32) of them received a platinum-based regimen. There were 35 (43.8%) pulmonary thromboembolism embolism (PTE) and 45 (56.2%) DVT patients. Among PTE patents, 14 (40.0%) were identified incidentally. Dyspnea and swollen of limb were the most common symptoms. Only 20.0% (16/80) patients received VTE prophylaxis.After a definite diagnosis of cancer, 73.8%, 77.5%, 82.5% and 85.0% of patients experienced an event within 3, 6, 9 and 12 months respectively. Up to April 2014, among 53 deceased patients, 77.4% (41/53) died from lung cancer, 9.3% (5/53) PTE while 13.2% (7/53) due to other causes. The cumulative mortality rates within 3, 6, 9 and 12 months after VTE event were 49.1%, 67.9%, 77.4% and 79.2% respectively.

Adenocarcimoma, advanced lung cancer, poor histodifferentiation and platinum-based chemotherapy regimen are the risk factors of VTE in lung cancer patients. Most events of VTE occur within 3-6 months after a diagnosis of lung cancer while most mortality cases within 1 year after VTE events.

To explore the relationship between angiotension-converting enzyme (ACE) I/D polymorphism and susceptibility to Henoch-Schönlein purpura or Henoch-Schönlein purpura nephritis (HSP/HSPN) especially among Chinese children.

The publications up to December 31, 2013 from PubMed, Embase, Google Scholar, Springer Link, Highwire, Cochrane, ISI, CNKI and Wanfang databases were searched for relevant literature on the association between ACE I/D polymorphism and pediatric HSP/HSPN.Heterogeneity was evaluated.And Stata 12.0 was used to assess the association strength in terms of odds ratio (OR) and 95%CI.

A total of 11 case-control studies fulfilled the inclusion criteria.And 5 articles were indentified for analyzing the relationship between ACE I/D polymorphism and pediatric HSP risk, involving 512 cases and 631 controls.Significantly risks of HSP were found (D/I: OR(95%CI)=1.23(1.04-1.46), P<0.05; DD/DI+ II:OR(95%CI)=1.24(0.77-2.00), P>0.05 and II/DD+ DI: 0.68(0.52-0.90),P<0.05). Nine articles were indentified for analyzing the relationship between ACE I/D polymorphism and pediatric HSPN risk, involving 446 cases and 877 controls.Significant risks of pediatric HSPN were found (D/I:OR (95%CI) =1.52(1.14-2.04), P<0.05; DD/DI+ II:OR(95%CI)= 1.85(1.06-3.21), P<0.05; II/DD+ DI:OR(95%CI)= 0.62(0.47-0.82), P<0.05).

In different ethnic groups, genotype DD of ACE I/D may increase the risk of pediatric HSP/HSPN and thus constitute a risk factor.Genotype II of ACE I/D may decrease the risks of pediatric HSP/HSPN and it may be a constitutively protective factor for pediatric HSP/HSPN.

To explore the accuracy of intraocular lens (IOL) power calculation with non-history method using the keratometric value derived from one zone of Orbscan Ⅱ topography after laser in situ keratomileusis (LASIK).

For this retrospective study, 20 eyes from 20 patients undergoing myopic LASIK were included from August 2008 to November 2011. Posterior corneal curvature in peripheral 7 to 10 mm fitting zone of postoperative cornea was measured with Orbscan Ⅱ topography. The ratio between anterior cornea and posterior cornea was used to calculate the preoperative total corneal power of each eye. The predicted postoperative spherical equivalent was calculated by the calculated preoperative total corneal power, power of implanted IOL, refractive error before cataract surgery and eye length from IOL-Master into the double-K method for SRK-T formula. The predicted postoperative spherical equivalent was also calculated by double-K method for SRK-T formula with clinical history. The mean difference between actual and predicted postoperative spherical equivalent, i. e. mean absolute error (MAE), were compared.

(1) Non-history method: MAE of 11 eyes was within ±0.5 D (55%), MAE of 15 eyes within ±1.0 D (75%) and MAE of all eyes within ±2.0 D. (2) Clinical-history method: MAE of 10 eyes was within ±0.5 D (50%), MAE of 14 eyes within ±1.0 D (70%) and MAE of all eyes within ±2.0 D. (3) Comparison of non-history and clinical-history methods: The MAE of non-history method was (0.61±0.59) D and the MAE of clinical-history method (0.68±0.55) D. Paired t-test showed no statistically significant difference between two methods (t=-1.248, P=0.227).

The non-history method using the keratometric value derived from one zone of Orbscan Ⅱ topography after LASIK provides an accurate calculation of IOL power and it can be used as a substitute for incomplete clinical data.

To explore the perioperative and long-term oxygenation status after uvulopalatopharyngealplasty (UPPP) in patients with obstructive sleep apnea syndrome (OSAS) and evaluate the predictive performance of STOP-BANG questionnaire and modified Epworth sleepiness scale(mESS) scales.

Oxygen saturation was continuously monitored with pulse oximeter wristwatch for up to 72 h postoperatively in 46 patients undergoing UPPP. They were followed up after 3 years with polysomnography, STOP-BANG questionnaire and mESS scales.

Oxygen saturation significantly improved postoperatively. The mean SPO₂ was 96.6% during 1 to 4 hour after extubation, 94.9% on POD1, 95.3% on POD2 and 91.1% on pre-operation respectively. The differences were statistically significant (Z=1.000, P<0.01). However, there were still episodes of hypoxemia, especially during 1st postoperative night(Z=-3.601 4, P<0.01). There was no difference(t=1.029, P>0.05) in mean SPO₂ between pre-operation (89.72±4.88)% and 3 years (88.84±6.16)% after UPPP.

Although UPPP significantly improves oxygen saturation in OSA patients, hypoxemic episodes still occur in the first 24 hours after surgery, especially during the first postoperative night. UPPP does not improve long-term hypoxemia.

To evaluate the prognostic effects of radial artery access (RA) versus femoral artery access (FA) in octogenarians undergoing percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS).

From January 2008 to January 2013, 279 octogenarians with ACS underwent PCI.PCI was performed through RA in 125 patients and FA in another 154.Clinical and procedural characteristics, combined endpoints including death, acute myocardial infarction, stroke, and major bleeding, and peripheral vascular complications were obtained from both groups.

The clinical baseline characteristics of two patient groups, including target vessel location, lesion type, number of implanted stents, fluoroscopy duration and utilization of contrast media had no statistical difference.Femoral approach was associated with a higher rate of ST elevation myocardial infarction (STEMI) than radial approach (27.9% vs 11.2%, χ ²=11.868, P<0.05). Procedural rate of success, fluoroscopy duration and utilization of contrast media were equivalent with both approaches.Radial approach was associated with a higher crossover rate (10.4% vs 3.9%, χ²=4.599, P<0.05) to alternate access site compared with the femoral approach.No difference in combined endpoint during 30 days after PCI including death, acute myocardial infarction, stroke and major bleeding was found between two groups (P>0.05). However, ambulation time (4.2±0.9 vs 19.3±4.1h,t=40.381, P<0.01), incidence of access site bleeding (2.4% vs 7.8%, χ²=3.943, P<0.05), hematoma (2.4% vs 9.1%, χ²=5.398, P<0.05), pseudoaneurysm (0.0% vs 5.2%, χ²=4.950, P<0.05) and vascular complications (4.8% vs 19.5%, χ²=13.231, P<0.01) were significantly lowered in radial approach group.Multivariate regression analysis identified radial approach as an independent negative predictor of postprocedural vascular complications (OR=0.329, 95%CI: 0.124-0.517, P<0.05). Female gender (OR=1.955, 95%CI: 1.326-2.248, P<0.05)and utilization of glycoprotein Ⅱb/Ⅲa receptor antagonist (OR=2.787, 95%CI: 2.435-3.071, P<0.01) were independent predictors of postprocedural vascular complications.

Compared with femoral approach, radial approach significantly reduces the vascular complications of PCI in octogenarians with ACS.However, PCI through RA is not associated with reduced combined endpoint at 30 days in octogerians with ACS.

To identify the potential risk factors for the development of chronic renal allograft failure in renal transplant recipients.

The data of 235 renal transplant recipients followed up for over 1 year were observed prospectively.And their risk factors were identified with multivariate Logistic regression analysis.

Forty-seven patients were diagnosed as chronic allograft failure (CAF). Multivariate risk factor analyses revealed that early (OR, 2.12; P<0.01) and late (OR, 4.54;P<0.001) acute rejection episodes, HLA-mismatch (≥3), HLA antibody production, viral infection, proteinuria, high serum triglyceride, recipient age (OR, 2.24;P<0.01) and males (OR, 1.63;P<0.05) were significant risk factors.Late acute rejection (> 3 months post-transplantation) was more important than early acute rejection with regards to the development of CAF.Delayed graft function and cyclosporine concentration were not associated with the development of CAF.

Both immunologic and non-immunologic risk factors are involved in the development of CAF.Predicating the risks of developing CAF at an early stage, before any deterioration of graft function, is of vital importance for the improvement of renal allograft survival and may guide individualized therapy.

To explore the protective effects of peroxisome proliferator-activated receptor-α (PPAR α) in D-GalN/LPS-induced acute liver failure (ALF) and its pathogenetic mechanism.

C57BL/6 mice were randomly divided into control, ALF, WY14643, 3-MA+ WY14643, siAtg7+ WY14643 and control siRNA+ WY14643 groups (n=8 each). For inducing ALF, the mice were injected intraperitoneally with D-GalN (700 mg/kg) and LPS (10 μg/kg). The selective activator of PPAR α-WY14643 (6 mg/kg) and autophagy inhibitor 3-MA (10 mg/kg) were administered via tail vein at 2 hours prior to D-GalN/LPS exposure.The autophagy inhibitor siAtg7 (50 μmol·L ^-1·kg^-1) and control siRNA (50 μmol·L ^-1·kg^-1) were dosed via tail vein at 48 hours prior to D-GalN/LPS exposure.At 6 hours after D-GalN/LPS dosing, the mice were anesthetized and blood sample collected.Liver samples were freshly harvested for preparing mRNA.Liver histology and serum levels of aminotransferase (ALT), aspartate aminotransferase (AST) were measured as markers of hepatic damage.Autophagy related genes (ATG5, ATG7, LAMP1), inflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CXCL-1, CXCL-10) were detected by real-time quantitative PCR.Differential protein expressions of LC3, ATG5, ATG7, LAMP1 in autophagy pathways were detected by Western blotting.

Compared with the model group, the hepatic architecture of WY14643-treated mice was better preserved.And the serum levels of ALT and AST were significantly lower ((486±56)vs(2 705±423)U/L, (795±115)vs(3 709±820)U/L, both P<0.05) while the expression of autophagy related gene LAMP1 and protein levels were significantly higher(mRNA: 4.28±0.57 vs 2.67±0.43,P<0.05). As compared with WY14643-treated ALF, the mice receiving 3-MA or ATG7-specific siRNA suffered severe acute liver failure again as evidenced by worse preserved hepatic architecture, significantly higher levels of ALT and AST ((2 563±576), (2 148±221) U/L and (3 474±858), (3 305±632) U/L, allP<0.05)and mRNA levels of proinflammatory cytokines and chemokines(allP<0.05).

PPARα-mediated induction of autophagy ameliorates liver injury in ALF by attenuating inflammatory responses.Thus it may become a potential target for ALF treatment.

To explore the effects of antibiotics plus efflux pump (EPI) inhibitors on mutant selection window of Pseudomonas aeruginosa in vitro.

In standard strains, the minimum inhibitory concentrations (MICs) of meropenem, ceftazidime, amikacin and ciprofloxacin alone were measured. Then the MICs of four antibiotics respectively plus EPI, including reserpine, omeprazole, azithromycin, carbonyl cyanide m-chlorophenyl- hydrazone (CCCP) and Phe-Arg-β-naphtylamide (PAβN), were measured by checkerboard test. And the mutant prevention concentrations (MPC) of antibiotics alone and antibiotics plus different EPIs were also measured by agar dilution method. Selection indices (SI) were acquired through MPC divided by MIC. Similarly, the SI of meropenem, ceftazidime and ciprofloxacin which respectively plus amikacin and amikacin plus ciprofloxacin were measured. In clinical strains, MIC, MPC and SI of antibiotics alone and four antibiotics plus CCCP were measured.

In standard strains, the SI of meropenem, ceftazidime, amikacin and ciprofloxacin alone were >32, >32, 16 and 16. After adding EPI, the SI of four antibiotics were 16, 16, 16, 8 (reserpine), 16, 32, 16, 8 (omeprazole), 8, 16, 16, 8 (azithromycin), 8, 8, 16, 8 (CCCP) and 8, 16, 16, 8 (PAβN). The SI of meropenem, ceftazidime and ciprofloxacin plus amikacin were 4, 4, 8. And the SI of amikacin plus ciprofloxacin was 4. In clinical strains, the SI of ciprofloxacin significantly decreased after adding CCCP.

Both MIC and MPC of meropenem, ceftazidime and ciprofloxacin decreased significantly after adding EPI. The mutant selection window decreased when ciprofloxacin was combined with CCCP.

To explore the in vitro differentiation of rat amniotic fluid-derived mesenchymal stem cells (AF-MSCs) into type Ⅱ alveolar epithelial cells (AECⅡ).

Flow cytometry was used to analyze the phenotypes of AF-MSCs from 10 pregnant Sprague-Dawley rats. And the Oct-4 mRNA expression level was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Rat embryonic stem cell was used as a positive control. According to different culturing methods, AF-MSCs were randomly divided into 5 groups of A (control group), B, C, D and E. After in vitro differentiation, SPA, SPB, SPC, SPD and TTF1 mRNA expressions were detected by qRT-PCR, SPA and SPC protein expressions measured by immunofluorescence and lamellar bodies observed by transmission electron microscopy.

AF-MSCs could grow spirally in L-DMEM medium containing 20% fetal bovine serum and 4 μg/L basic fibroblast growth factor. The expressions of such surface antigens of AF-MSCs (third passage) as CD29 (99.1±7.9)%, CD44 (99.2±7.4)%, CD73 (75.6±5.2)% , CD90 (98.9±8.1)%, CD105 (92.9±7.3)% and CD166 (89.3±6.7)% were positive while CD34 and CD45 were negative.And the expression of Oct-4 mRNA (relative quantity: 0.690±0.059) was significantly lower than rat embryonic stem cells (relative quantity: 1.000±0.002) positive control group ( P<0.01). Afterin vitro differentiation, the expressions of SPA, SPB, SPC, SPD and TTF1 mRNA and SPA and SPC protein were negative in group A and positive in group B. The expressions of SPA, SPB, SPC, SPD and TTF1 mRNA (relative quantity: 0.426±0.043, 0.368±0.028, 0.492±0.058, 0.327±0.024 and 0.183±0.018) and SPA and SPC protein in group B were significantly higher than other groups (all P<0.01). Lamellar bodies could be found in the differentiated cells of group B.

Rat AF-MSCs from amniotic fluid may differentiated into AECⅡ like cells in vitro.

Portal pulmonary hypertension (POPH) is a disease characterized by progressive increase of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) and normal pulmonary wedge pressure (PCWP) due to pulmonary vascular disease on the basis of portal hypertension^[1]。 2% to 6% of patients with portal hypertension are diagnosed with POPH 4 to 7 years after onset, and 1% to 2% of patients with cirrhosis are complicated with POPH. This proportion is higher when patients with end-stage liver disease are evaluated before liver transplantation^[2]。 Most patients with POPH have no obvious symptoms in the early stage and often miss the best opportunity for treatment. From January 2012 to June 2013, four POPH patients were admitted to Beijing Chaoyang Hospital, which are summarized as follows.

A 62-year-old female was admitted to the hospital on 1 December 2011 due to abdominal distension for 4 months. The patient has developed abdominal distension without trigger since July 2011, progressive increase of abdominal circumference, decreased appetite, and depressed edema of both lower limbs. No fever, abdominal pain, and decreased urine output. No rash, limb sensory disturbance. The routine blood test in the local hospital showed that hemoglobin (Hb) was 84 g/L, and white blood cells and platelets were normal; Urine occult blood positive (+), protein (+); erythrocyte sedimentation rate 36 mm/1 h; C-reactive protein (CRP) 7.94 mg/L; normal liver function; Blood urea nitrogen 11.77 mmol/L, creatinine 123.5 μ mol/L, creatinine clearance 37 ml/min; Abdominal ultrasound: medium to large volume of fluid accumulation in the abdominal cavity; CT: Old tuberculosis in upper lobes of both lungs, peritoneal effusion. Multiple ascites examinations showed no tumor cells. Oral administration of furosemide was ineffective. Abdominal distension gradually worsens, urine output decreases, and 3 000 ml of ascites need to be discharged every other day. The patient's spirit has been acceptable since the onset of the disease. In the past 2 months, if ascites is not drained, the body weight will gain 1 kg every day. Previous history: He underwent surgical treatment for tuberculosis of left knee 50 years ago, and was treated with antituberculosis for 1 year after surgery. Has a history of hypertension for more than 10 years and is not well controlled. Hypothyroidism was found in June 2011 and was replaced with thyroxine. History of marriage and childbirth: The daughter was diagnosed with thalassemia (heterozygous), and the husband died of "cirrhosis" (details unknown). Physical examination: vital signs stable, anemic appearance, hemangioma visible on the skin of the trunk. Several swollen lymph nodes can be accessed under the bilateral axillary, with tough texture and no tenderness, and a diameter of about 1.5 to 2.0 cm. There was no distension in the jugular vein, the heart boundary was not large, and grade II soft blowing-like murmur could be heard in the precordial area. No abnormalities were found in the physical examination of both lungs. Abdominal distension, abdominal circumference 89 cm, no abdominal wall varices. There is no tenderness or rebound pain in the whole abdomen. High abdominal wall tension. The liver was 6 cm below the costs, tough in texture, uneven in surface, with nodular sensation, untouched spleen, mild percussion pain in the liver area, positive mobile voicing, and depressed edema in both lower limbs.

Glucocorticoids are steroid hormones secreted by the adrenal cortex under the control of the hypothalamus-pituitary-adrenal axis (HPA). Endogenous glucocorticoids have a certain circadian rhythm, and play a very important role in physiological and pathological states such as body development, immune response, endocrine metabolism, inflammatory response, etc. Because hormones have strong anti-inflammatory activity and immunomodulatory effects, they are commonly used in clinical practice to treat inflammatory diseases, such as bronchial asthma (asthma for short), ulcerative colitis, and various skin diseases; Because hormones also have certain pro-apoptotic properties, they are also mostly used to treat hematological tumors such as Hodgkin's lymphoma, human acute lymphocytic leukemia (ALL), multiple myeloma and other neoplastic diseases and autoimmune diseases.

Colorectal cancer (CRC) is the third largest tumor in incidence worldwide after lung cancer and breast cancer. According to the Global Cancer Epidemiological Statistics (GLOBOCAN), about 600,000 people die from CRC worldwide every year^[1], making it the fourth most fatal tumor in the world. Although the incidence of CRC in China was far lower than that in western developed countries in the past, in the past 40 years, with the rapid development of economy, the change of national living habits and dietary structure and the acceleration of aging process, the incidence and mortality of CRC in China have shown an obvious upward trend. CRC has become one of the major malignant tumors that endanger the health of our residents, which brings a heavy burden to the social economy and medical undertakings. Colorectal cancers are mostly sporadic, and 70% ~90% of colorectal cancers are related to diet factors. A large number of immigrant epidemiological and etiological studies suggest that the difference in the incidence of colorectal cancer between East and West is mainly due to dietary nutritional factors. Therefore, optimal diet will be beneficial to prevent and treat most colorectal cancers.

A male patient suffered from sudden severe pain in lower abdomen and testis in August 2009, and was intermittently treated with cefuroxime lipid, tinidazole, azithromycin and levofloxacin for 81 days. After drug withdrawal, coagulase-negative staphylococci were generally cultured in semen; Anaerobic and L-type culture of viscoactinomycetes. Since there is no American Institute of Clinical and Laboratory Standards (CLSI) standard for Actinomyces viscosus, only the antimicrobials with large inhibition zones are listed here,>26 mm are: cefepime, amoxicillin, imipenem, doxycycline, minocycline, tetracycline, vancomycin, teicoplanin, tigecycline. On the 20th day of intravenous injection with amoxicillin, there was severe pain. After 2 weeks of switching to doxycycline, the symptoms improved. On the 7th day of changing cefepime, I felt severe pain again. Actinomycetes viscosus and Enterococcus faecium (associated bacteria) were cultured from semen. With vancomycin, amoxicillin/clavulanate potassium intravenously for 1 month, the pain was somewhat relieved, but it worsened after 2 days of stopping the drug. L-type viscoactinomycetes were cultured in urine (slow growth, 9 days), and viscoactinomycetes were grown in prostate fluid enrichment culture for 4 days. Those with inhibition zone>30 mm were minocycline, tetracycline, spectinomycin, amikacin and netilmicin; Rifampicin 42 mm. The patient went to Peking University First Hospital for treatment in June 2010. Since the susceptibility test for L-type bacteria is completed after restoration of the bacterial cell wall, drugs that do not act on the cell wall should be selected. After using rifampicin and minocycline for 5 days, the stinging pain in the urethra disappeared. Multiple reexaminations of urine routine were negative, and no viscoactinomycetes were detected in urine culture. On 22 Jul 2010, there were still L-type myxoactinomycetes in prostatic fluid culture, with rifampicin plus tetracycline. On September 8, 2010, semen culture showed no bacterial growth in L-type, and Actinomyces viscosus was cultured anaerobically. He continued to take tetracycline plus rifampicin. After that, according to the pain perception of the patient, it was estimated that rifampicin was resistant. On March 8, 2011, semen culture, L-type bacteria cultivated Actinomycetes myxosus, and the associated bacteria were Streptococcus hemolyticus. Change minocycline, tetracycline, doxycycline wheel medication. Once netilmicin was used, the patient's symptoms improved significantly, and his semen changed from yellow to white. Due to adverse reactions, it was changed to gatifloxacin or minocycline. In September 2010, MRI showed that the prostate was enlarged by 4.2 cm ×3.1 cm ×3.0 cm, the signal of the right side of the prostate was abnormal, the bladder wall was uniformly thickened, and the morphology and signal of the seminal vesicles, testes and epididymis on both sides were not abnormal. April 2011 re-examination of enlarged prostate volume , 4.5 cm ×3.8 cm ×3.5 cm. Partial prostate resection was performed in April 2011. Under the pathological microscope, broken prostate tissue, interstitial hyperplasia and focal glandular infarction were seen. After that, gatifloxacin or minocycline was taken once every 7 days. There was still viscoactinomycetes growth in semen bacterial culture in April 2012. After taking the medicine, the patient occasionally drank alcohol, and felt that the effect of the medicine was enhanced. After this combination, the lower abdominal pain and testicular pain gradually disappeared. Until March 2013, the semen bacterial culture was negative.

A 16-year-old male was seen in the Department of Stomatology, School of Stomatology, Lanzhou University, mainly due to pain in the right mandible and teeth for more than 2 weeks and poor chewing ability of teeth. The patient is 1.58 m tall and weighs 46 kg. The parents deny the marriage of close relatives. The patient has a full-term natural delivery, and his life and study are not restricted. The patient had a large head and a small face, the width of the acromion was 31 cm, the width of the medial canthus was 4.5 cm, the width of the fontanel was 2 cm, both shoulders were drooped, and the range of motion of the shoulder joint was increased. In the mouth, except for the lower occlusal central incisor and four upper and lower first molars, all the rest are deciduous teeth. X-ray examination showed that the frontal bone was square and round, the skull was obviously enlarged and unbalanced, and the head was large and the face was small (FIGS. 1A, B)。 The transverse diameter of the skull is enlarged, the bottom is relatively narrow, the fontanel is large but not closed, the cranial sutures are widened and separated, and the intersutural bone can be seen. The thoracic collapse was bell-shaped, and the ribs were thinned and walked abnormally. The distance between the clavicle and the acromion and sternum was widened, the scapula was high, the coracoid process and acromion of the bilateral scapula were dysplasia, the scapular glenoid became smaller and shallower, and the articular surface was hardened. Abnormal proportion of proximal phalanges to middle and distal phalanges in both hands (Figure 1C)。 The proportion of metatarsal, proximal phalanges and middle distal phalanges of both feet was abnormal, and the development of the first distal phalanges of both feet was small (Figure 1D)。 Curved tomography shows multiple embedded supernumerary teeth in the upper and lower premolar regions (Figure 1E)。 The size and morphology of the bilateral clavicle were abnormal, the right clavicle was short in development, and the middle part of the bone of the left clavicle was discontinuous, showing two primary ossification centers (Figure 1F)。 Chromosomal examination showed no abnormalities. Peripheral blood genomic DNA of patients and parents was extracted, and the exon of osteoblast transcription factor (RUNX) 2 gene was sequenced. Two missense mutation sites were found in Exon3 and Exon4 of RUNX2 gene of patients and parents (Table 1), c.432G>A and c.778C>T, respectively, and no mutation sites were seen in the remaining exons. c.432 G>A is a synonymous mutation found in the patient's mother and therefore is not a pathogenic mutation. While the Denovo mutation site c.778C>T present in the patient (Figure 2) is a pathogenic mutation that causes the arginine at position 190 of the RUNX2 protein to mutate to tryptophan.

The child was a 7-year-old male. He was admitted to hospital on 20 November 2013 due to recurrent abdominal pain for 2 months and aggravation for half a month. Abdominal pain is mainly in the middle and upper abdomen, unbearable, refusing to press, abdominal pain can be alleviated when curled up, abdominal pain is aggravated when lying flat, accompanied by nausea and vomiting, vomit is the stomach content, and abdominal pain is slightly relieved after vomiting, accompanied by abdominal distension. The hospital diagnosed "acute necrotizing pancreatitis", given fasting, acid suppression, somatostatin, anti-infection, placement of nasojejunal tube for enteral nutrition and other treatments, and found pseudocyst formation, the child still had recurrent abdominal pain, for endoscopic retrograde cholangiopancreatography (ERCP) admitted to the gastroenterology ward of our hospital. Physical examination: No yellowing stain on the skin. Flat and soft abdomen, positive epigastric tenderness (+), negative rebound pain (–), muscle tension (–), presence of liver voiced area, and mobile voiced sound (–). After admission, they were treated with fasting, anti-infection, acid suppression, somatostatin, and fluid rehydration support. On November 21, they underwent ERCP + papillary sphincterotomy (EST) + endoscopic biliary drainage (ERBD) + nipple dilation. Small stones were seen in the lower part of the common bile duct on angiography. Small stones and bile flowed out were seen by nipple incision 0.2 cm. One 5Fr was placed^*4 cm bile duct stent, was transferred to the pediatric ward on November 25 for continued treatment, and was diagnosed as: acute necrotizing pancreatitis (severe); Pseudocyst of pancreas; choledocholithiasis; Acute cholangitis. On the same day, a nasojejunal tube was placed in the descending part of the duodenum under the guidance of a gastroscope, and enteral nutrition such as formula milk was performed, gradually increasing the amount, and intermittent injection was used for about 15 minutes each time, with an interval of 3 hours. The child experienced abdominal pain again at noon on November 30th, which was considered to be an enlarged pancreatic pseudocyst (about 10 cm in diameter measured by ultrasound). He was treated with fasting and anti-infection again. On December 2nd, he underwent drainage of pancreatic pseudocyst under B-ultrasound localization. Enteral nutrition started on December 3rd, and gradually transitioned to oral liquid diet. On December 17th, a small amount of chyloid substance was drained from the drainage tube of the child, which was considered to be chyloid leakage. On December 21st, the child's enteral nutrition and oral dietary calories could meet the physiological needs, urinary amylase dropped to normal, and there was no abdominal pain, so he was discharged with a drainage tube.

A 40-year-old male was admitted to hospital for "repeated coughing and expectoration for more than 20 years and dyspnea after activity for more than 2 years". More than 20 years ago, the patient coughed repeatedly without obvious trigger, and had a large amount of yellow thick phlegm, occasionally bloodshot, accompanied by left chest pain. Repeated visits to the local hospital showed left pleural effusion. At that time, the pulmonary artery systolic pressure was about 35 mmHg (1 mmHg =0.133 kPa) by ultrasound, and the diagnosis was "tuberculosis and tuberculous pleurisy". Diagnostic treatments such as streptomycin, isoniazid, rifampicin and ethambutol were given successively, but the effect was not good. Subsequently, the patient's cough, expectoration symptoms and left pleural effusion appeared repeatedly, and the anti-tuberculosis regimen was adjusted many times without obvious efficacy. Two years before admission, the patient began to show decreased activity tolerance, edema of both lower limbs and gradually aggravated, and pleural effusion was also more serious than before. Echocardiography revealed severe pulmonary hypertension. Chest CT showed scattered fibrous cord shadows, patch shadows and small nodules in the left lung. The bronchial wall of the left lung was thickened and the lumen was slightly enlarged. Pleural effusion: albumin 26.8 g/L, nucleated cells 450×10⁶/L, mucin assay (–), glucose 6.35 mmol/L, sodium 141.9 mmol/L, chloride 111.1 mmol/L, lactate dehydrogenase 38 U/L; Exfoliative cytology showed more proliferative mesothelial cells and a small number of lymphocytes. Left pleural biopsy showed fibrous tissue proliferation with a small amount of proliferating mesothelial cells. Erythrocyte sedimentation rate, serum C-reactive protein normal, tuberculosis antibody (–). Still considering "tuberculous pleurisy", it was adjusted to D1321ThOK regimen to continue anti-tuberculosis for 1 month. The patient still had repeated left chest pain and pleural effusion, and came to our hospital again in June 2013; Echocardiography showed enlarged right heart, smooth left atrial apex, and only right pulmonary venous return was detected; Cardiovascular multi-slice spiral CT pulmonary angiography (Figure 1) shows stenosis of the left pulmonary artery trunk and its branches, and compensatory thickening of the right pulmonary artery trunk and the right inferior pulmonary artery; The left pulmonary vein is slender (left superior pulmonary vein main trunk about 2 mm, left inferior pulmonary vein main trunk about 1 mm); Both merge into atresia at the left atrium; The right pulmonary vein was thickened, with a maximum diameter of 23 mm ×28 mm. Final diagnosis: congenital heart disease (left pulmonary vein atresia). The patient refused pneumonectomy and requested discharge. After more than half a year of follow-up, the patient still had repeated left pleural effusion. At present, pleural effusion is palliatively drained in local hospitals regularly and followed up closely.