Volume 98  ·  Issue 32  ·  2018

Prostate cancer (PCa) is one of the most common malignant tumors in men and one of the leading causes of cancer-related death in men worldwide, ranking second in cancer mortality among men^[1]。 Although the understanding and treatment of PCa has improved greatly over the past few years, the molecular regulation and pathogenesis of PCa cell growth have not been fully elucidated. Patients with early PCa are usually treated with surgery and radiation therapy^[2]For advanced PCa, the treatment strategy based on endocrine therapy is often used clinically, that is, androgen removal therapy^[3]。 However, continuous deandrogenation still inevitably leads to the development of androgen-dependent PCa to androgen-independent PCa, i.e. castration-resistant PCa (CRPC), which causes great obstacles to the clinical treatment of PCa^[4]。 Studies have found that autophagy plays a key role in the process of castration resistance produced by deandrogenation treatment. Autophagy is the process of degrading abnormal cellular components into nutrients such as amino acids, lipids, nucleotides, and carbohydrates and redistributing them to cells for recycling. The degraded cellular components are first surrounded by a double membrane structure to form phagocytic vesicles, which gradually fuse and mature into autophagosomes, and then autophagosomes combine with lysosomes to form autophagic lysosomes, thus realizing the recycling and reuse of degradation products^[5]。 It has long been widely believed that autophagy plays diametrically opposite roles at different disease stages. For example, in the early stages of tumorigenesis, autophagy can reduce the accumulation of abnormal genes and proteins to inhibit tumorigenesis. However, increasing evidence suggests that autophagy plays a protective role against advanced PCa, especially under conditions such as hypoxia, nutrient supply deficiency, chemotherapy, etc., and can promote tumor cell survival and adaptation by eliminating the accumulation of toxic proteins and providing nutrient sources^[6]。 Moreover, the self-recycling supply of nutrients and energy by autophagy may even further promote the anabolic process of the tumor, thereby accelerating the development of prostate cancer^[7]。 Therefore, autophagy is a "double-edged sword" for the occurrence and development of PCa. It is particularly important to understand the important role of autophagy in the development mechanism of PCa and explore the potential of autophagy for the treatment of PCa. The role of autophagy in the development of prostate cancer and its molecular mechanism are described below.

Benign prostatic hyperplasia (BPH) is the most common benign disease with urinary disorders in middle-aged and elderly men. About 30% of patients with BPH will progress to advanced stage, and about 40% of patients with advanced BPH need surgical treatment. Prostatectomy is an effective means to treat advanced BPH. Most resections of the prostate require removal of the urothelium of the urethra in the prostate region.

Epidermal growth factor receptor (EGFR) gene mutation is the most common driver gene mutation in non-small cell lung cancer (NSCLC) in East Asian population, with an incidence of 30% ~40%^[1,2]。 Several previous studies have supported that EGFR-tyrosine kinase inhibitor (TKI) monotherapy is the standard treatment regimen for patients with locally advanced or metastatic NSCLC with EGFR gene mutations, but most patients will develop drug resistance 9 to 14 months after administration^[3,4,5,6]Among them, missense mutation in exon 20 of EGFR gene (i.e. T790M mutation) is the most dominant type of drug resistance mutation. At present, the positive rate of T790M mutation in EGFR-TKI resistant tissue samples is about 60%^[7,8]However, the positive rate of T790M mutation in plasma samples varies greatly based on different methods, ranging from 23% to 63%^[9,10,11]。

To investigate the role of hypoxia-inducible factor-1α (HIF-1α) and β-catenin in radioresistance of prostate cancer (PCa) cells.

Two PCa cell lines, LNCaP and C4-2B, were grouped as: negative control (no treatment), HIF-1α overexpression group (transfected with HIF-1α plasmids), and β-catenin silencing group (transfected with HIF-1α plasmids and β-catenin-shRNA). Cell proliferation, cycle, invasion, and radiosensitivity were measured under normal or hypoxic condition. Radiosensitivity was tested in two mice PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model).

In both LNCaP and C4-2B cells, HIF-1α transfection led to an enhanced β-catenin nuclear translocation, while β-catenin silencing inhibited the β-catenin nuclear translocation. Enhanced β-catenin nuclear translocation caused by HIF-1α overexpression resulted in enhanced cell proliferation and invasion, altered cell cycle distribution, reduced apoptosis, and improved non-homologous-end-joining (NHEJ) repair under irradiation condition. In vivo imaging of orthotopic models showed that HIF-1α overexpression LNCaP cells produced tumors with 3-fold volume (P=0.003 1) and 2-fold wet weight (P=0.039 4) than those by negative control cells at day 21, and β-catenin silencing cells aberrantly reduced both tumor volume ( P=0.000 3) and wet weight (P=0.017 5) than HIF-1α overexpression cells. In addition, C4-2B subcutaneous models showed similar tumor promotion effects induced by HIF-1α overexpression (tumor volume:P=0.000 1 and wet weight: P=0.047 3) and suppressive effects by β-catenin silencing (tumor volume: P<0.000 1 and wet weight:P=0.022 1) as LNCaP orthotopic xenograft with regard to tumor volume and wet weight.

HIF-1α overexpression enhanced β-catenin nuclear translocation, which led to the activation of the β-catenin/NHEJ signaling pathway and increased cell proliferation, invasion, and DNA repair. These results suggest that HIF-1α overexpression led to radioresistance of PCa cells.

To develop a nomogram based on prostate imaging reporting and data system version 2 (PI-RADS v2) to predict clinically significant prostate cancer in patients with a prior negative prostate biopsy.

The clinical and pathological data of 231 patients who underwent repeat prostate biopsy and multiparametric MRI (mpMRI) were reviewed. Based on PI-RADS v2, the mpMRI results were assigned as PI-RADS grade from 0 to 2. A Logistic regression nomogram for predicting the probabilities of clinically significant prostate cancer were constructed. The performances of the nomogram were assessed using area under the receiver operating characteristic (ROC) curve, calibrations and decision curve analysis.

Of the total 231 repeat prostate biopsy patients, clinically significant prostate cancer was detected in 59 cases(25.5%). In multivariate Logistic regression analysis, age, prostate specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE) and mpMRI results were significant independent predictors of the diagnosis of clinically significant prostate cancer (P<0.05). The nomogram with super predictive accuracy were constructed (AUC=0.927,P<0.001), and exhibited excellent calibration. Decision curve analysis also demonstrated a high net benefit across a wide range of threshold probabilities .

PI-RADS v2 combined with age, PSA, PV and DRE can predict the probability of clinically significant prostate cancer in patients with negative initial biopsies. The nomogram generated may help the decision-making process in patients with prior benign histology before the performance of repeat biopsy.

To evaluate the effect of arterial blood HCO₃^- level on the accuracy of NoSAS questionnaire screening for obstructive sleep apnea hypopnea syndrome (OSAHS).

The hospitalized patients with suspected OSAHS were recruited from March 2016 to December 2017 in the First Affiliated Hospital of Guangzhou Medical University. NoSAS scores, blood gas analysis and polysomnography (PSG) were performed in these patients. Patients were divided into non OSAHS group and mild, moderate and severe OSAHS group according to the PSG results. According to the NoSAS questionnaire score, the patients were divided into OSAHS high-risk group and low risk group. The correlation between arterial blood HCO₃^- level and apnea hypopnea index (AHI) was analyzed. The receiver operating characteristic (ROC) curve was plotted to analyze the accuracy of HCO₃^- prediction OSAHS. Predictive parameters(sensitivity, specificity, positive and negative predictive values)for NoSAS scores and HCO₃^- level were calculated.

A total of 243 patients with suspected OSAHS were included, including 186 males (76.5%), 57 females (23.5%), age (49±13) years, body mass index (BMI) (26.9±4.4) kg/m^2, and neck circumference (38.6±4.5) cm. The HCO₃^- level was positively correlated with AHI (r=0.206, P=0.001). The proportion of patients with HCO₃^- level ≥26 mmol/L in non-OSAHS group was lower than that in OSAHS group (13.0% vs 34.5%, P=0.004); the proportion of patients with HCO₃^- level ≥26 mmol/L in severe OSAHS group was higher than that in mild OSAHS group (37.7% vs 15.0%, P=0.008), and there was no difference in the ratio of patients with severe OSAHS and moderate OSAHS (37.7% vs 35.3%, P=0.767). The specificity of OSAHS predicted by HCO₃^- level 25 and 26 mmol/L was 69.6% and 87.0%, respectively. With the NoSAS score of 8 or 7 as cutoffs for analysis, the sensitivity for OSAHS was 61.9% and 79.2%, the specificity for OSAHS was 57.4% and 40.4%, respectively. With the addition of HCO₃^- level ≥ 26 mmol/L to the NoSAS score ≥ 7, the specificity for OSAHS improved to 93.6%, while the sensitivity decreased to 27.4%.

Combined with the arterial blood HCO₃^- level, the specificity of the NoSAS questionnaire increases and the sensitivity decreases.

To study the association between Thymidine Phosphorylase (TYMP) genetic variation and clinical outcomes and safety of postoperative colorectal cancer (CRC) patients.

A total of 235 patients with colorectal cancer underwent surgical treatment were included in this retrospective analysis. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative CRC patients were analysed.

Located in the upstream, 5633C>T was of clinical significance. The prevalence of 5633C>T in TYMP among the CRC patients were as follows: CC genotype 149 cases (63.40%), CT genotype 73 cases (31.06%), TT genotype 13 cases (5.54%), minor allele frequency of 5633C>T is 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.313). CT genotype and TT genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Overall Survival (OS) of CT/TT genotype and CC genotype were 5.8 and 4.5 year, which was statistically significant (P=0.009). Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT or TT genotypes were significantly higher than those of the wild type CC genotype patients (P=0.019). And the safety analysis showed that the incidence of grade 3 hand-foot syndrome among CT/TT genotype patients were higher than that of CC genotype patients (33.72% vs 20.13%, OR=1.68, P=0.021).

The polymorphism 5633C>T of TYMP may impact the prognosis of CRC patients received adjuvant chemotherapy by influencing the mRNA expression of TYMP.

To observe the impact of first-line chemotherapy on renal function in patients with unresectable/metastatic upper tract urothelial carcinoma(UTUC).

A total of 222 (130 males and 92 females) unresectable/metastatic upper tract urothelial carcinoma patients were included in the study between January 2005 and May 2017, with age of 29 to 87 (62.4±10.1) years old. The serum creatinine level and estimated glomerular filtration rate (eGFR) were compared before and after first-line chemotherapy. And predictive factors for decreased renal function were analyzed in logistic regression model.

After the first-line chemotherapy, the average serum creatinine level increased, with a median changing value of 1.5 μmol/L. Howerver, the eGFR improved, with a median changing value of 0.5 ml·min ^-1· (1.73 m²)^-1, but the differences were not statistically significant (all P>0.05). In 149 patients who were treated with cisplatin-based chemotherapy, the average serum creatinine level increased by 1.31 μmol/L and eGFR improved by 0.14 ml·min^-1·(1.73 m²)^-1, but the differences were not statistically significant (P>0.05). In multivariate logistic regression model, age more than and equal to 60 years old (OR=0.88, P=0.745) and cisplatin-based chemotherapy (OR=0.95, P=0.893) did not increase the risk of renal dysfunction after first-line chemotherapy. If the time interval between surgery and first-line chemotherapy was more than 1 year, the risk of renal dysfunction due to chemotherapy decreased (OR=0.54, P=0.196). Eastern Cooperative Oncology Group Performance Status (ECOG PS) Scale≥1 (OR=1.81, P=0.131), anemia before treatment (OR=1.14, P=0.764), the cycles of first-line chemotherapy (OR=1.41, P=0.398) may lead to increase the risk of renal dysfunction, but the differences were not statistically significant. However in the patients who accepted nephrectomy, the risk of renal dysfunction after chemotherapy increased, but the difference was still not statistically significant (OR=3.06, P=0.089).

First-line chemotherapy, especially the cisplatin-based regimen, had no significant impact on renal function in the patients with UTUC. Nephrectomy maybe a predictive risk factor for decreased renal function after chemotherapy. Adequate assessment of renal function before treatment, hydration and close monitoring during chemotherapy can effectively protect renal function of the patients.

To analyze high risk factors, therapeutic regimen and prognosis of patients with pulmonary mucormycosis.

A retrospective analysis was performed on the clinical data of 25 patients who were diagnosed as pulmonary mucormycosis in the First Affiliated Hospital, School of Medicine, Zhejiang University, between January 2009 and December 2017.

Univariate analysis revealed that no risk factor had significant effect on prognosis of these 25 cases, while multivariate logistic regression analysis confirmed that the exposure to antifungal drugs was correlated to worse prognosis(P=0.046). All 4 patients who had received surgical lesionectomy were cured, and 8 patients who had not received any therapy targeted to mucormycosis were all dead. Seven of 13 patients received antifungal drug to mucormycosis were effective, with an effective rate of 54.0%. The mortality rate of the operative group was lower than that of the non-operative group (P=0.026), and the prognosis of the patients received drug treatment was better than patients without treatment(P=0.022). There was no significant difference in the prognosis between groups of single drug or combination of amphotericin B and posaconazole.

Pulmonary mucormycosis is more likely to occur in patients with tumor of the hematopoietic and lymphoid tissues, immunosuppression after solid organ transplantation, long-term glucocorticoid usage and diabetes. Surgical lesionectomy can improve the survival rate, and the treatment with amphotericin B and /or posaconazole can also improve the prognosis of the patients.

To explore the clinical significance of serum bone metabolites β C-termianl telopeptide of type Ⅰ collagen(β-CTX), Procollagen type Ⅰ N-terminal peptide(PINP) concentration and ratio of beta -CTX/PINP in multiple myeloma bone disease (MMBD) and bone metastases.

A total of 31 cases of MM, 46 cases of bone metastases and 12 healthy controls were enrolled in the department of hematology, oncology and physical examination center of Henan Provincial People′s Hospital respectively from October 2016 to October 2017. According to the imaging findings, MMBD was divided into 0-4 grades, group A included the patitents with grade 0-2 of osteopathy (n=8), and group B included the grade 3-4 (n=23). After two courses of chemotherapy, the curative effect was evaluated. MM group were divided into effective group (above partial remission , n=22) and uneffective group (unreached partial remission, n=9). ELISA method was used to detect the concentration of serum beta -CTX and PINP, and the ratio of beta -CTX/PINP was calculated.

The serum beta -CTX concentration in newly diagnosed MM, bone metastases and healthy control were (3 563 ± 544)ng/L, (6 690±343)ng/L, (2 726±1 026)ng/L (χ²=22.207, P<0.001), PINP concentration were (72 ± 14) ng/L, (112 ± 62) ng/L, (171 ± 62) ng/L (χ²=7.418, P=0.024) , and beta -CTX/PINP ratio were 93±19, 141±21, 17±8 (χ²=20.192, P<0.001), the differences were statistically significant. The ratio of initial MM beta -CTX/PINP was higher than that of healthy control (P=0.001). The concentration of beta -CTX (P=0.003) and the ratio of beta -CTX/PINP(P<0.001) in bone metastases were higher than those in healthy controls. The serum concentration of beta-CTX in newly diagnosed MM was lower than that in bone metastases (P<0.001). Before chemotherapy, the serum levels of beta -CTX and PINP in A and B groups were not statistically significant, but the ratio of serum beta -CTX/PINP in A group was lower than that in group B, and the difference was statistically significant. After two courses chemotherapy, the concentration of serum beta -CTX (P=0.023) and the ratio of beta -CTX/PINP (P<0.001) were decreased in MM group. There were no significant difference of serum beta -CTX, PINP concentration, and beta-CTX/PINP ratio before and after treatment in Group A. Patients in the group B, there was no significant difference in the changes of serum PINP concentration, but both serum beta -CTX concentration and beta-CTX/PINP ratio decreased after two courses[(4 027 ± 648)ng/L vs (2 370± 460) ng/L,P=0.043; 111± 23 vs 30± 6, P=0.002]. The ratio of serum beta-CTX/PINP decreased in the effective group, and the difference was statistically significant. There was no significant difference in serum beta-CTX, PINP concentration and beta-CTX/PINP ratio before and after treatment in the uneffective group.

There is a difference between newly diagnosed MMBD and bone metastases in serum beta-CTX, which might be helpful for differential diagnosis, and the ratio of beta-CTX/PINP is positively correlated with the severity of MMBD, which might be used to evaluate the severity of bone disease and have a certain monitoring significance for the treatment of MM.

To analyze risk factors and drug resistance of community-onset methicillin-resistant staphylococcus aureus (CO-MRSA) infection through the investigation of patients infected with CO-MRSA.

The clinical data of 97 cases infected with community-onset staphylococcus aureus (COSA) was collected in this hospital from July 2016 to June 2017. Epidemiological survey method and the variables were determined according to expert consultation, literature and practical work experience.

Among 97 patients infected with COSA, the diagnosis rate of CO-MRSA was 21.65%(21/97). The drug sensitivity results showed that: CO-MRSA was high resistant to erythromycin, tetracycline and clindamycin, and the drug resistance rate exceeded 50%. Multiple variables were analyzed by Logistic regression. The usage of antimicrobial agents in the past three months and the history of hospitalization within one year were the independent risk factors. The MRSA infection rate was 57.89%(11/19) of the persons who had taken antibacterial agents in the recent three months.The MRSA infection rate was 48.28%(14/29) of the persons who had been hospitalized in the past one year. OR value of two risk factors was respectively 10.006(95%CI: 2.200-45.519, P=0.030) and 11.519(95%CI: 2.405-55.177, P=0.002).

Most COSA is sensitive to methicillin, but CO-MRSA is multidrug resistant and has more risk factors. The clinicians should reasonably use the antibacterial agents according to the drug sensitivity in order to prevent the occurrence of multidrug resistant MRSA.

To investigate the effect and mechanism of celastrol on free fatty acids (FFAs)-induced HepG2 cells.

Cultured human HepG2 cells were transfected with toll-like receptor 4 (TLR4) siRNA, and the interference efficiencies were examined by real-time PCR. HepG2 cells were treated with FFAs and celastrol, and the untreated cells were used as a normal control (NC). Deposition of lipids in the HepG2 cells were visualized by Oil Red O staining. The protein expression of TLR4 and downstream inflammatory mediators [myeloid differentiation factor 88 (MyD88), nuclear factor (NF)-κBp65, interleukin (IL)-1β and tumor necrosis factor α (TNF-α)] in the HepG2 cells were determined by Western blotting. The significance of the data obtained was evaluated using analysis of variance (ANOVA).

Red lipid droplets were extensively deposited in HepG2 cells after 0.5 mmol/L FFAs induction and significantly decreased in the celastrol-treated group. The protein expression of TLR4 and downstream inflammatory mediators (MyD88, NF-κBp65, IL-1β and TNF-α) in the FFAs-induced HepG2 cells increased significantly compared with those of the NC group (allP<0.05), and were suppressed in TLR4 siRNA-treated and celastrol-treated group (TLR4: 0.69±0.14, 1.63±0.12 vs 2.46±0.23; MyD88: 1.21±0.12, 1.35±0.18 vs 1.62±0.19; NF-κBp65: 1.69±0.14, 1.54±0.36 vs 2.19±0.47; IL-1β: 1.51±0.16, 1.45±0.38 vs 1.82±0.27; TNF-α: 1.60±0.14, 1.41±0.29 vs 1.88±0.19) (allP<0.01). Co-treatment with TLR4 siRNA and celastrol further reduced the expression of inflammation mediators compared with those of the TLR4 siRNA-treated group (MyD88: 1.09±0.23 vs 1.21±0.12; NF-κBp65: 1.24±0.20 vs 1.69±0.14; IL-1β: 1.28±0.31 vs 1.51±0.16; TNF-α: 1.10±0.29 vs 1.60±0.14) (allP<0.01).

Celastrol exerts its protective effect partly via inhibiting the TLR4-mediated signaling pathways in the steatotic HepG2 cells.

A 35-year-old female was seen in the outpatient department of Peking Union Medical College Hospital on October 25, 2017 due to "polydipsia, polydipsia, polyuria, amenorrhea for 1 and a half years and galactorrhea for 6 months". In April 2016, the patient developed polydipsia, polydipsia (5 L/d), polyuria (4~5 L/d), nocturia 5~6 times/night, self-complaining of dry skin, no menstrual cramps in that month, and no other accompanying symptoms. In September 2016, I went to a local hospital and found that my visual acuity in both eyes decreased slightly, without strabismus, diplopia, visual field defect, and eyelid ptosis. B-ultrasound of uterus showed thinning of the endometrium (0.2 cm), smaller uterine body (3.8 cm ×2.6 cm ×2.6 cm), and smaller bilateral ovaries (2.4 cm ×1.2 cm); Prolactin (PRL) 2.90 nmol/L (reference value:<1.37 nmol/L), estradiol 32.94 pmol/L (reference: 73.2-322.1 pmol/L), follicle stimulating hormone (FSH) 3.09 U/L and luteinizing hormone (LH) 0.85 U/L. Enhanced magnetic resonance imaging (MRI) of the pituitary gland: the suprasellar region occupies a mass, with a size of 0.6 cm ×0.6 cm ×0.8 cm, which is closely related to the pituitary stem, and no significant enhancement is observed. After treatment with progesterone and traditional Chinese medicine (specific unknown), menstruation still did not resume. In April 2017, the patient found that after squeezing the breast, milky discharge was visible, milky white, without bloodstreaks, so he went to the neurosurgery department of another hospital for examination: urine specific gravity: 1.005; There were no obvious abnormalities in blood routine and blood biochemistry; Antinuclear antibody (ANA) (+) 1:320 (homogeneous spot type), anti-ribonucleoprotein (RNP) antibody (+), anti-SSA antibody (+), proliferative nuclear antigen antibody (PCNA) (+); anti-neutrophil cytoplasmic antibody (ANCA) (−); a tumor marker (-); blood alpha-fetoprotein (AFP), human chorionic gonadotropin (β-HCG) (−); Cerebrospinal fluid: conventional, biochemical (-), looking for tumor cells (-). The other hospital considered "suprasellar area occupation, central diabetes insipidus", and gave desmopressin acetate tablets (micing) (oral, 25 μ g/time, twice/d) and bromocriptine (oral, 1.25 mg/time, once/d). The patient's symptoms of polydipsia, polydipsia and polyuria were significantly relieved, drinking water 2 L/d, urine volume 1.5 L/d, nocturia 1~2 times/night, but there was still no menstrual cramps, and milky white liquid still spilled out after squeezing the breast, so bromocriptine was stopped in September 2017. During the course of the disease, there was no fever, oral ulcer, joint pain, bone pain and other symptoms, and he was admitted to our hospital for further diagnosis and treatment. Since the onset of the disease, the patient's spirit, sleep and appetite are good, his stool is normal, his urine is as mentioned above, and his weight has not changed significantly. Past history: Cesarean section at 42 weeks of gestation in 2011 gave birth to a 3 kg male baby. History of marriage and childbirth: age-appropriate marriage and childbirth, spouse physical health. Menstrual history: Menarche 14 years old, menstrual days 4 days, menstrual cycle 25~28 days, last menstrual on May 10, 2016. Personal history and family history are no different.

A 76-year-old female was admitted to the First Affiliated Hospital of Zhejiang University School of Medicine on October 11, 2017 due to chest tightness, dizziness for 1 year and syncope twice 12 years after coronary stent implantation. The patient underwent coronary stenting 12 years ago due to coronary atherosclerotic heart disease (specifics unknown) and regularly took isosorbide mononitrate and aspirin. One year ago, chest tightness, accompanied by dizziness, and a squeezing sensation occurred during the attack. It occurred once a few days and lasted for several minutes. It was induced when tired or mood fluctuated and could be relieved by itself. Half a month ago, syncope occurred after standing for a long time (about 20 min), and automatically regained consciousness after 1~2 min. Before syncope, there were symptoms of chest tightness and dizziness. Tracing back to the medical history, there was a similar attack 1 year ago. At present, the patient still has chest tightness and dizziness, which is aggravated after activity, mildly limited activity, and it is difficult to go up the stairs. For further diagnosis and treatment, the outpatient clinic was admitted to the hospital with "hypertension, coronary atherosclerotic heart disease".

A 60-year-old male was admitted to the gastroenterology ward of Peking Union Medical College Hospital on September 12, 2017 for diagnosis and treatment due to "chronic diarrhea for 3 months, abdominal pain with bloody stool for more than 1 month". Three months before admission, the patient developed diarrhea, loose stools 3 to 4 times a day, without pus and blood, and colonoscopy in an external hospital showed mild mucosal edema of ascending colon to sigmoid colon, without erosion or ulcer. Self-administered antidiarrheal drugs are ineffective. One month ago, the patient had sudden periumbilical colic without obvious trigger, and the pain score was 5 points, accompanied by brown bloody stool defecation of about 500 ml, tenesmus and then severe, no fever, vomiting, amaurosis, etc., and abdominal pain improved after defecation. The next day, blood and watery stool were discharged 20 to 30 times, 20 to 50 ml each time. A large number of red and white blood cells were found in routine fecal examination in other hospitals, and occult blood was positive; Erythrocyte sedimentation rate was 18 mm/h, hypersensitive C-reactive protein 77 mg/L, and anti-neutrophil cytoplasmic antibody was negative. Colonoscopy showed congestion, edema, roughness, erosion, bleeding and ulcer formation in the mucosa of ascending, transverse, descending and sigmoid colon, but no abnormalities in the rectum were found. Pathological report: Chronic inflammation of mucosal tissue with formation of small focal crypt abscess. Abdominopelvic enhanced CT: Irregular thickening and visible enhancement of the local intestinal wall of the transverse colon. Considering not excluding inflammatory bowel disease, prednisone 40 mg/d (equivalent to 1 mg/kg per day), mesalazine 4 g/d, intestinal probiotics and enteral nutrition were given. Abdominal pain was relieved compared with before, but blood and watery stool were still discharged 10 to 12 times a day, 20 to 50 ml each time. After 2 weeks of adequate hormone therapy, he turned to watery stools more than 10 times a day. Weight loss of 14 kg after onset. Deny repeated oral ulcers, vulvar ulcers, joint swelling and pain, etc. Past history: In 2016, I underwent thoracoscopic enlarged thymectomy due to "thymoma and myasthenia gravis", and regularly took bromophenostigmine after the operation. Hyperlipidemia, denied history of coronary heart disease without taking lipid-lowering drugs. Personal History: Has a long history of smoking and denies alcoholism. Admission physical examination: vital signs were stable, the superficial lymph nodes of the whole body were not swollen, surgical scars were visible on the chest, the heart and lungs were not different, the abdomen was soft, the middle and upper abdomen were mild tender, no rebound pain, the liver and spleen were not reached under the costs, and the abdominal mass was not reached, intestinal sounds were 3~4 times/min, and there was no edema in the lower limbs.

The patient, a 52-year-old male, was admitted to the Department of Metabolic Endocrinology, Xiangya Second Hospital, Central South University on July 14, 2017, mainly due to "fever for 3 months, polyuria and polydipsia for 2 months". The patient went to the local hospital on April 27, 2017 due to fever and oliguria. The blood creatinine was measured at 799.6 μ mol/L, and the epidemic hemorrhagic fever antibody was positive. He was diagnosed with hemorrhagic fever with renal syndrome and acute renal failure. After symptomatic treatment such as anti-infection and hemodialysis, the symptoms of fever and oliguria were relieved, and the blood creatinine was re-measured at 253.3 μ mol/L. On May 21st, he developed symptoms of polyuria and polydipsia, drinking 4,000~5,000 ml of water and 4,000~6,000 ml of urine daily. The local hospital considered the polyuria stage of renal failure and gave symptomatic treatment, but the effect was not good. Symptoms of anorexia, nausea, fatigue, fear of cold and loss of libido gradually appear. Thyroid function checked locally on June 15: free triiodothyronine (FT₃) 3.23 pmol/L (reference value: 3.54-6.57 pmol/L), free thyroxine (FT₄) 5.43 pmol/L (reference value: 11.40-23.20 pmol/L), thyroid stimulating hormone (TSH) 0.156 mU/L (reference value: 0.510-4.940 mU/L); Sex hormone test: testosterone 1.06 nmol/L (reference value: 8.20~27.0 nmol/L), luteinizing hormone (LH)<0.07 U/L (reference value: 1.48-9.40 U/L), follicle stimulating hormone (FSH) 0.45 U/L (reference value: 1.40-17.80 U/L); Magnetic resonance imaging (MRI) of the pituitary gland: thinning of the pituitary gland with mild enhancement, considering adenohypopituitarism. Prednisone was given 5 mg/time, 2 times/d orally, and levothyroxine sodium tablets 50 μ g/time, 1 time/d orally after 1 week. The symptoms of nausea, fatigue and cold sensitivity were alleviated, and the symptoms of polyuria and polydipsia were still present. The daily urine volume was 4,000~5,000 ml, and the water consumption was 3,000~4,000 ml. In order to clarify the cause of polyuria, we were admitted to our department. Past history: I was diagnosed with type 2 diabetes 1 year ago without treatment. On April 21st, I went to a local hospital due to dry mouth and dizziness. My fasting blood glucose was checked at 22.3 mmol/L, and I was given "recombinant human insulin combined with insulin glargine" treatment. After the blood glucose improved, the dose was gradually reduced to discontinuation. The insulin was used for half a month. After discontinuation, the fasting blood glucose was monitored at 4~5 mmol/L, and the blood glucose was 5~7 mmol/L 2 hours after meals. Personal history: Born in Xiangyin County, Hunan Province, living alternately in Xiangyin County and the suburbs of Guangzhou. All house mice live in Guangzhou, but there is no direct contact, and there is no similar disease in his family.

Asthma is a chronic airway disease characterized by reversible airflow obstruction, airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling. Obesity is considered one of the most important public health problems of the 21st century. Many studies have shown that^[1]There is a significant correlation between obesity and the onset of asthma. The relationship between the two is increasingly valued, and the 2012 edition of the International Consensus on Childhood Asthma lists obesity asthma as a special phenotype of asthma^[2]。 Obesity asthma is characterized by more severe symptoms, unstable or lack of asthma control, predominantly non-eosinophilic airway inflammation and steroid resistance, and therefore its clinical treatment faces greater challenges^[3]。 It is currently believed that there are at least two distinct major phenotypes of obesity asthma: an early-onset allergic type that is complicated with obesity and a late-onset non-allergic type that occurs only in the context of obesity. Both phenotypes have asthmatic manifestations, but they respond differently to weight-loss treatments. Significant improvement in symptoms and AHR after weight loss in patients with delayed onset non-allergic obese asthma, whereas only symptoms and no improvement in AHR in patients with early onset allergic obese asthma^[4]。 AHR, as an essential feature of asthma, can be produced in simply obese individuals^[5]The above differences also exist in different phenotypes of obese asthma. Therefore, the study of the mechanism of AHR in obesity and asthma is an important entry point for the study of the potential association mechanism between obesity and asthma.

Induced sputum technique is a non-invasive diagnostic and detection method that promotes the production and discharge of sufficient sputum by inhalation of hypertonic saline. The induced sputum comes from the lower respiratory tract, is not easily affected by squamous epithelial cells, and can better represent the pathophysiological characteristics of the lung^[1]。 At the beginning of the 21st century, the application of sputum induction technique in respiratory diseases is still relatively simple. It is mainly applied to bronchial asthma (asthma) and chronic obstructive pulmonary disease (COPD), which are two chronic airway inflammatory diseases, with good safety and repeatability^[2,3]。 A large number of previous studies have evaluated the type and level of airway inflammation mainly by detecting the inflammatory cell count and inflammatory factor level in induced sputum. However, with the updating of technology and knowledge in the field of respiratory diseases and the rapid progress of molecular biology and immunology, sputum induction technology has been widely used in respiratory diseases in recent years. The research findings, new technologies and extended applications of sputum induction technique in respiratory diseases in the past 10 years are summarized as follows.

Intravitreal injection of drugs is a common treatment in ophthalmology. In recent years, the surgical volume of intravitreal injection of drugs has increased exponentially. According to Medicare data, the proportion of intravitreal drug injections in ophthalmic surgery increased from 0.55% (2 922/527 050) in 2000 to 86.91% (2 619 950/3 014 629) in 2014^[1]。 For blinding eye diseases such as wet age-related macular degeneration and diabetic macular edema, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs has become the first treatment option. Due to the increasing number of patients undergoing cataract surgery after intravitreal injection of anti-VEGF drugs in the past, in recent years, researchers have begun to pay attention to the correlation between the history of intravitreal injection of anti-VEGF drugs and cataract surgery complications. This article mainly discusses the research progress on the correlation between intravitreal injection of anti-VEGF drugs and posterior capsule rupture, postoperative endophthalmitis and intraocular hypertension in cataract surgery.