Volume 94  ·   Issue 18  ·  2014

At present, pancreatic cancer is still a major problem in the treatment of malignant tumors, and surgical resection is the only hope for long-term survival of pancreatic cancer patients. However, the 5-year survival rate is only about 20%^[1]。 Studies have confirmed that the margin condition after surgical resection of pancreatic cancer is one of the most important factors to determine the prognosis of patients. However, more than 80% of patients have local recurrence within 1 year after surgery, which suggests that most of the current "radical" resection cannot achieve the purpose of radical cure^[1]。 On the other hand, true R0 resection (no microscopic tumor residue at all margins) can significantly improve disease-free survival and overall survival in patients with pancreatic cancer^[2]。 Therefore, scholars have made a series of improvements to standard pancreaticoduodenectomy with the aim of increasing the R0 resection rate in patients with pancreatic head cancer, thereby improving long-term survival.

The recent phenomenon of violence against doctors in China has attracted the attention of the international medical community.Lancet^[1,2,3]AndBMJ^[4]All tracked and commented on. These articles believe that the violence against doctors in China has seriously violated the safety, rights and dignity of doctors' practice, and doctors feel great pressure and challenges in their practice. If such incidents cannot be well prevented, the medical industry will It will be difficult to attract outstanding and sufficient talents to join. While calling for "zero tolerance" for such violent incidents, the crux of China's current medical and health system is the deep-seated reason leading to these violent incidents. Therefore, the reform of medical and health policy aiming at promoting the trust between doctors and patients is a top priority. Understanding the international consensus, research progress and governance experience on violence in medical places can provide ideas and reference for formulating relevant health policies in China.

Medical disputes have become one of the difficult and hot issues in social problems. Medical disputes are mainly resolved through consultation and reconciliation between doctors and patients, administrative mediation and civil litigation. From a practical point of view, these approaches can't solve disputes well, the relationship between doctors and patients is still tense, and the resolution of medical disputes is still a thorny problem. New Dispute Resolution Mechanism-People's Mediation Mechanism of Medical Disputes is to introduce the people's mediation system with Chinese characteristics into the settlement of medical disputes^[1]。 Starting with the results of questionnaire survey and related interview data of patients accepted by Beijing People's Mediation Committee for Medical Disputes (MAC) from October to December, 2012, this paper preliminarily discusses the problems existing in the operation of people's mediation mechanism for medical disputes in Beijing and possible improvement countermeasures.

"The hardest part for a clinician is not the technology, but the ethics." That's one of my "quotes." Here I will reflect with readers through two true stories about the ethics of technology, money, doctors and patients.

In recent years, cases of killing doctors have frequently appeared in newspapers, and the majority of medical staff generally feel dangerous and angry. Surprisingly, parts of the public were indifferent to the atrocities, and some even felt "happy". In response to this chaos, people can't help but ask: What is wrong with the doctor-patient relationship in China, and why exactly, this article adopts Milne's right theory^[1]From the perspective of basic rights protection, the case of killing doctors is analyzed, and it is found that the basic rights of patients' minimum requirements are not fully guaranteed, which is the fundamental reason for the tension between doctors and patients in China at this stage.

In recent years, with the rapid development of medical technology, the hardware environment of hospitals has improved obviously. However, the tension between doctors and patients in China has not been alleviated, and the incidence of medical disputes is increasing in some areas^[1]Violent medical injuries occur from time to time, especially within 10 days from October 17 to 27, 2013, there were 6 medical injuries of patients nationwide, and many medical staff were seriously injured or even killed. The reasons for the current tense doctor-patient environment include system level, hospital and doctor level, patient level, media level and so on^[2]。 No suffering can justify a patient's violence against a doctor, whether or not the perpetrator was punished in time, what should a doctor do in the current environment? Don't let kids study medicine? Choose to give up, wait passively, or be proactive and improve? Be honest with it? The author thinks that doctors should take the lead, start from themselves, and actively create a harmonious doctor-patient environment from the following aspects^[3]。

In recent years, the frequency and malignancy of "violent medical injury cases" are on the rise. On February 25, 2014, a nurse in Nanjing Stomatological Hospital was attacked by a patient's family; On February 17th, 2014, the director of ENT Department of Qiqihar Beiman Special Steel Hospital was killed by a 19-year-old patient; In October 2013, patients in Wenling First People's Hospital attacked medical staff, causing one death and two injuries; In September 2013, a female stomatologist in Beijing Tongren Hospital was slashed by a patient; In November 2012, a patient in the Second Affiliated Hospital of Anhui Medical University killed a nurse and slashed four medical staff; In April 2012, the chief physician of ENT Department of Peking University People's Hospital was chased and stabbed by a patient, and the deputy director of emergency department of Beijing Aerospace General Hospital was stabbed by a patient on the same day; In March 2012, the doctor of the First Affiliated Hospital of Harbin was killed... On March 22, 2014,LancetAnother commentary article "Why is hospital violence so serious in China"^[1]Recently, the frequent medical violence in China has attracted the attention of the international medical community. Now, a preliminary analysis is made on the reasons for the frequent occurrence of violent medical injuries.

To explore the clinical efficacies of bilevel positive airway pressure (BiPAP) ventilation in uremic patients with acute heart failure.

Fifty uremic patients with acute heart failure on dialysis were recruited from February 2008 to October 2012 at our center. All of them received angiectasis, heart strengthening and continuous renal replacement therapy (CRRT), but their clinical symptoms had no relief 30 min later. Non-invasive ventilation was administered immediately. And the parametric changes of systolic pressure (SBP), diastolic pressure (DBP), heart rate (HR), breathing rate (R), partial pressure of oxygen (PaO₂) and carbon dioxide (PaCO₂) were observed at 30 min after conventional therapy and 1, 2 h later after non-invasive ventilation. And the levels of blood brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF) and clinical manifestations were observed at 2 h after non-invasive ventilation.

Their clinical symptoms improved after BiPAP ventilation. And SBP, DBP, P, R and BNP showed a declining tendency, but PaO₂ and LVEF showed a rising trend. Compared to conventional therapy, SBP ((160±17), (147±18) vs (172±20) mmHg) (1 mmHg=0.133 kPa), DBP ((90±9), (85±10) vs (98±10) mmHg), HR ((95±8), (88±9) vs (102±12) times/min), R ((20±3), (17±4) vs (26±3) times/min) declined while PaO₂ ((87±9), (94±12) vs (81±9) mmHg) increased significantly, 1, 2 h later after noninvasive ventilator treatment (all P<0.05); the blood level of BNP decreased ((1084±398) vs (2686±576) μg/L), LVEF elevated (52%±7% vs 39%±9%) significantly, 2 h later after noninvasive ventilator treatment (bothP<0.01).

As a safe and effective intervention, early use of BiPAP ventilator-assisted breathing in uremic patients with acute heart failure effectively ameliorates their clinical manifestations and improve heart function.

To explore the expressions of protein and mRNA of disabled-2 (Dab2) and extracellular signal-regulated kinase1 (ERK1) in esophageal squamous cell carcinoma tissue (ESCC) and their clinical significance.

The expressions of protein and mRNA of Dab2 and ERK1 were detected in ESCC (n=59), atypical hyperplasia (n=27) and normal esophageal mucosa (n=36) tissues by immunohistochemistry, in situ hybridization and reverse transcription polymerase chain reaction (RT-PCR).

The expressions of protein and mRNA of Dab2 were lesser in ESCC than those in atypical hyperplasia and normal esophageal mucosa tissues (23.7% vs 94.4%, 44.4% and 18.6% vs 97.2%, 33.3%). And the expressions of protein and mRNA ERK1 were higher in ESCC than those in atypical hyperplasia and normal esophageal mucosa tissues (81.4% vs 44.4%, 63.0% and 78.0% vs 30.6%, 51.9%) (all P<0.05). Additionally, the expressions of protein and mRNA of Dab2 and ERK1 were closely related with lymph node metastasis in ESCC tissue and the expressions of protein and mRNA of ERK1 closely related with the depth of tumor invasion in ESCC tissue (allP<0.05). Furthermore, the results of correlation analysis revealed that expressions of protein and mRNA of Dab2 and ERK1 in ESCC had a negative correlation (allP<0.05).

The expressions of protein and mRNA of Dab2 and ERK1 play important roles in the infiltration, metastasis and carcinogenesis of ESCC and their effects may be antagonistic to each other.

To explore the clinical characters of adrenal medullary hyperplasia (AMH).

The clinical data of 7 cases of AMH admitted from 1996 to 2013 were analyzed with a review of literature.

There were 3 males and 4 females with a median age of 36 (23-69) years. All had hypertension at first diagnosis and 2 were paroxysmal. Computed tomography (CT) scan revealed unilateral adrenal nodule in all cases, including left (n=5) and right (n=2) side. The diameter of nodules was 0.9 cm to 3.0 cm. Hypokalemia was found in 2 cases. And 24-hour output of urine catecholamine was higher than normal level in 2 cases. An abnormal rise of 24-hour output of urine free cortisol was found in 1 case with a lower level of adrenocorticotropic hormone (ACTH) simultaneously while a lower level of plasma renin activity in vertical position was found in another case. Three patients received ¹³¹I-meta-iodobenzylguanidine scan and one had positive result. Pre-operative diagnosis included pheochromocytoma (n=2), adrenocortical adenoma (n=3) (2 aldosterone-producing adenomas, 1 Cushing adenoma) and undetermined adrenal tumor (n=2). All underwent surgery, including unilateral adrenalectomy (n=4) and resection of adrenal disease (n=3). All cases had a pathologic diagnosis of AMH. One had concurrent Cushing adenoma while another with cortical hyperplasia. One case achieved normotension postoperatively while others showed varying decreases of blood pressure, but remained hypertensive.

With a common feature of hypertension, AMH is difficult to diagnose preoperatively. CT scan has a certain diagnostic significance and a definite diagnosis depends on pathological examination; because of inaccurate preoperative and intraoperative diagnosis, the extent of surgery may be incomplete and results in unsatisfied outcomes.

To explore the expression of cyclooxygenase-2 (COX-2) in lowly differentiated nasopharyngeal carcinoma and examine its relationship with cervical lymph node metastasis.

On the basis of COX expression, a total of 104 patients with lowly differentiated squamous cell carcinoma NPC were divided into 2 groups of COX-2 high-expression and COX-2 low-expression. The influence on prognosis was assessed by retrospective analysis.

The overall positive rate for COX-2 staining was 78.8%(82/104). The rate of patients with lymph node metastasis was significantly higher than that in those without (84.5% vs 55.0%, χ ²=6.765, P=0.009). Further comparison showed that patients with age <45 years and neck lymph node metastasis had higher rate of COX-2 high expression than those with age >45 years and no cervical lymph node metastasis (58.7% vs 37.7%, χ ²=4.439, P=0.035; 52.4% vs 25.0%, χ ²=4.861, P=0.027). At the end of follow-up, the recurrence rate with inter-group statistical differences (χ²=4.786, P=0.029) was 32.7% (16/49) and 14.6% (8/55) respectively. Meanwhile, as compared with COX-2 high-expression group, the transferring rate in COX-2 low-expression group significantly decreased (17.7% vs 28.6%, χ ²=4.037, P=0.045). Multiple logistic regression analysis showed that COX-2 high expression was a risk factor of nasopharyngeal carcinoma recurrence [OR=2.039, 95%CI (1.042-5.875)].

COX-2 expression is up-regulated in lowly differentiated nasopharyngeal carcinoma tissues. And it may be risk factor influencing the prognosis of NPC.

To evaluate the genetic diagnostic feasibility of Bruton′s tyrosine kinase (BTK) gene in three families with X-linked agammagobulinemia (XLA) birth history, mutation analysis and prenatal genetic diagnosis of BTK gene for two families with XLA.

Polymerase chain reaction (PCR) was applied to amplify the regions of exon and exon-intron boundaries of BTK gene in 3 unrelated patients of XLA and their mothers from January 2011 to June 2012. The PCR products were further analyzed by direct sequencing. Prenatal genetic diagnosis was performed by chorionic villus sampling after genotyping of mothers of probands.

Three novel mutations of BTK gene were identified in 3 pedigrees of XLA. A missense mutation c. 1117C>A(p. L373I)were detected in pedigree 1. The mutation was possible damage by predicting in sillico. A nonsense mutation c. 126T>G(p. Y42X)was found in pedigree 2. A single base deletion mutation c. 1679delC(p. P560fsX10)was found in pedigree 3. The three mutations, p. L373I, p. Y42X and p. P560fsX10 were novel. The three novel mutations were absent in the 100 normal controls. The male fetus in pedigree 3 was free of mutations identical to the proband and the female fetus in pedigree 2 was a carrier. The two families continued the pregnancies and the infants showed no symptom of XLA after one year old.

Three novel mutations were identified. The mutations of p. Y42X and p. P560fsX10 in BTK gene may be the major causes of pedigrees 2 and 3 with XLA. The mutation p. L373I of BTK gene is possibly the cause of pedigree 1 with XLA, but functional verification is needed. For pedigree of XLA, direct sequencing of BTK gene is available for providing genetic counseling, prenatal diagnosis.

To analyze the influencing factors of pathologic complete response (PCR) to neoadjuvant chemotherapy in locally advanced breast cancer patients.

A retrospective study was conducted to analyze the clinical data of 620 locally advanced breast cancer patients at Henan Cancer Hospital between April 2003 to February 2013. After neoadjuvant chemotherapy, 94 patients achieved PCR. The correlation between clinicopathological factors and PCR was analyzed.

No significant correlations existed between PCR with patient age, menstrual status or pretherapeutic lymph node status. Increased chemotherapeutic cycles could improve the rate of PCR (14.1% or 19.5 %), but it had no statistical difference. The rate of PCR achieved by regimens of anthracycline plus taxane was higher (20.1%)than that by anthracycline-based regimens (12.7%). And the rate of PCR had significant difference between two regimens. In terms of biological indicators, PCR rate after neoadjuvant chemotherapy was associated with estrogen/progesterone receptor, but it had no correlation with Ki-67 index or the status of epidermal growth factor receptor. Logistic multifactorial analysis showed that tumor size ≤5 cm were significantly correlated with PCR. Trastuzumab could obviously increase the PCR rate (15.7% or 41.7 %) and there was statistical difference (P=0.031).

The regimens of anthracycline plus taxane can achieve a higher PCR rate. Patient age, menstrual status and pretherapeutic lymph node have no significant correlation with PCR. PCR rate is associated with the expression of ER/PR negative in breast cancer. Trastuzumab increase the PCR rate in the HER-2 positive patients. Tumor size ≤5 cm is a significant influencing factor of PCR rate.

To observe the pathologic effects of marrow hematopoietic cell with immunologic injury induced by infection immunity activation in patients with immune related hematocytopenia syndrome (IRHS) and elucidate its immunologic mechanism and clinical significance.

A total of 276 IRHS patients with acute and chronic infections were recruited from 2008 to 2013. ELISA was used to detect the levels of interleukin-6 (IL-6), IL-12, IL-17 and interferon gamma (IFN-γ) in peripheral blood sera of IRHS patients before and after therapy. Flow cytometry was performed to detect the proportion of lymphocyte subgroups in peripheral blood. Immunochemical staining was used to analyze the expressive states of peroxydase (POX), HLA-DR in bone marrow and non-specific esterase. The expressive states of CD4, CD8, CD56, IFN-γ, porforin, granzyme, FcγRⅡ, anti-human IgG, mannose receptor (MR), IL-12 and IL-17A in bone marrow cells and hematopoietic microenvironment were analyzed with immunofluorescence (IF). According to the above immunological indices, antibiotics were prescribed along with medaron and ciclosporin A (CsA).

Among 276 patients, the levels of IL-6, IL-12, IL-17 and IFN-γ were higher than those in control group(allP<0.05). After treatment, the cytokine levels above decreased to normal gradually. The levels of CD3⁺CD4⁺ T and NK cells increased respectively in those with concurrent viral or mycoplasma infection(54.23%±3.07% and 50.11%±3.09% vs 35.25%±5.16%, 22.71%±2.26% and 19.49%±2.07% vs 14.91%±4.87%). The proportions of CD3⁺CD4⁺ T and CD19⁺ B cells increased in sera of patients with bacterial infection(40.22%±4.31% vs 35.25%±5.16%, 29.01%±4.32% vs 11.56%±2.54%). But the proportion of CD3⁺CD8⁺ T cells increased in patients with viral infection of type B hepatitis(32.51%±3.44% vs 25.08%±4.43%)(all P<0.05). In patient marrow samples, dendritic cell, T lymphocyte, eosinophilic granulocyte and macrophage were activated to express many abovementioned immunological molecules. Both the destructive pattern of hemocyte and the degree of pathological lesion induced by these immunocytes were related with the cause of infection immunity activation and morbid state of patients. After individualized treatment, 264 patients showed elevated hemogram at 4-8 weeks while the relapse of 12 patients persisted until an initiation of cytotoxic drug and a gradual restoration of hemogram.

Infection is one of the most important factors of IRHS. Excessive activation of infection immunity may induce the disorder of immune system. Then immunocytes destroy or damage those hemocytes with pathological changes through different immunological pathways. The pathogenetic condition and outcome is related with infected pathogen and intrasubject immune state. Control of pathogenic microorganism infection and glucocorticoid treatment may suppress the excessive activation of immunocytes so as to become important preventive and curing measures of IRHS.

To explore the significance of 2-hour blood glucose after standardized steamed bread meal (SB-2 hBG) in diabetic screening.

A retrospective study was conducted for diabetic screening data of annual check-up at PLA General Hospital from May 1996 to June 2002. And 100 g standardized steamed bread meal test was performed for non-diabetic subjects. Those subjects with SB-2 h BG≥7.2 mmol/L underwent a 75 g oral glucose tolerance test (OGTT) within 2 weeks to determine whether the diagnosis of diabetes mellitus (DM) could be established (WHO, 1985, 1999, Diagnostic Criteria for Diabetes). By extracting the data for 7 consecutive years, we analyzed the significance and the cut-off point of SB-2 hBG in the diagnosis of DM and investigated the changes of blood glucose curves in different glucose tolerance status after different glucose loading tests.

A total of 3 343 subjects with complete information were recruited. There were 3 101 males and 242 females with an age range of 40-94 years. According to the results of OGTT, 429 (12.8%) subjects were diagnosed as DM, 1 405 (42.1%) were diagnosed as impaired glucose regulation (IGR) and 1 509(45.1%) had normal glucose tolerance (NGT). With a deterioration of glucose tolerance status, the difference between SB-2 hBG and OGTT-2 hBG increased gradually in 3 group(P<0.01), namely the NGT group 1.7 (0.8-2.8) mmol/L, IGR group -0.4(-1.2-0.6) mmol/L, DM group -2.7(-3.8-1.1) mmol/L. The cut-off points of FBG for the diagnosis of IGR and DM were 5.3 (sensitivity of 46.2%, specificity of 68.5%) and 5.6 (sensitivity of 57.4%, specificity of 76.4%) mmol/L respectively. The cut-off points of SB-2 h BG were 8.2 mmol/L for the diagnosis of IGR (sensitivity of 63.8%, specificity of 59.9%) and 9.2 mmol/L for the diagnosis of DM (sensitivity of 66.4%, specificity of 76.4%). If the cut-off point of SB-2 h BG was set at 7.2 mmol/L, the diagnostic specificity became quite low. However, at 11.1 mmol/L, the sensitivity was 31.5% and the specificity 95.7% for the diagnosis of DM. The coincidences of cut-off points of FBG and SB-2 hBG for the diagnosis of IGR and DM were equal (P>0.05). When the cut-off point of SB-2 h BG was set at 7.8 mmol/L, the sensitivity was 77.4% and the specificity 41.8% for the diagnosis of IGR. And it was much better than FBG at 5.6 mmol/L (P<0.01).

With a deterioration of glucose tolerance, the difference between SB-2 hBG and OGTT-2 hBG increases gradually. Compared to the diagnostic criteria of OGTT, the optimal cut-off points for the diagnosis of IGR and DM were 5.3 vs 5.6 mmol/L for FBG and 8.2 vs 9.2 mmol/L for SB-2 hBG respectively. For diabetic screening in middle-aged and elders, the cut-off points of FBG at 5.3 mmol/L and SB-2 hBG at 7.8 mmol/L are indicators for further OGTT.

To evaluate the serum HER2 ECD level and its significance in advanced breast cancer patients with different molecular subtypes.

A total of 322 advanced breast cancer patients were enrolled. The serum HER2 ECD concentrations were quantitatively detected by enzyme-linked immunosorbent assay(ELISA). Its relationship with clinicopathological characteristics and clinical significance were analyzed.

It was found that 55.9%(19/34)Luminal A, 42.7%(44/103) Luminal B-HER2(-), 70.6%(60/85)Luminal B-HER2(+), 73.8%(45/61)HER2-enriched and 23.1%(9/39)triple-negative patients had serum concentrations of HER2 ECD at least 15 ng/ml respectively. The prevalence of elevated ECD level in patients of different molecular subtypes differed significantly(P<0.001). Tissue HER2 status, number of metastatic sites, visceral metastasis, CA15-3 and carcinoembryonic antigen(CEA) levels exhibited statistically significant correlations with the prevalence of elevated serum HER2 ECD level. The serum concentrations of HER2 ECD decreased after effective targeted therapy in tissue HER2-positive patients.

The prevalence of elevated serum levels of HER2 ECD differed significantly in advanced breast cancer patients with different molecular subtypes. The serum HER2 ECD level may reflect both histological HER2 status and tumor load. And the dynamic changes of ECD concentrations are somewhat correlated with the efficacies of targeted treatment.

To explore the effects of metformin therapy on serum carbohydrate antigen 125 (CA125) levels and its related factors in type 2 diabetics with normal liver and kidney function.

Serum CA125 level was measured and compared for a total of 1 136 type 2 diabetics. They were assigned into groups according to gender, age and body mass index (BMI) and subgroups according to metformin dosing. Associations between CA125 and other variables were assessed with Spearman or Pearson′s correlation and multiple stepwise regression analysis.

The CA125 level of metformin group was significantly lower than that of non-metformin group (10.51(8.18, 13.80) vs 11.93(9.05, 15.52) U/ml, P<0.01). The CA125 levels of males aged 30-39 and 50-59 as well as females aged over 50 remarkably decreased after metformin dosing (allP<0.05). The difference of CA125 level between metformin and non-metformin groups in patients with normal BMI and obese females reached statistical significance (allP<0.05). The correlation analysis showed that serum CA125 level was positively associated with gender, HbA1c, glycated serum albumin, triglyceride, total cholesterol (P<0.05), but negatively with metformin and creatinine (P<0.01). Multiple stepwise regression analysis further revealed that GA, metformin dosing, gender and total glycerides were independent influencing factors of CA125 concentrations (allP<0.05).

Metformin dosing is an independent associated factor of serum CA125 levels reduction in type 2 diabetics, especially females.

To explore the effects of tripterygium wilfordii polyglucoside (TWP) on expression of Activin A (Act-A) and influence of transdifferentiation in renal tubulointerstitium of rats with diabetes nephropathy (DN).

A total of 40 male Wistar rats were randomly divided into normal control, DN model, irbesartan treatment and TWP treatment groups (n=10 each). The animal model of DN was established by an injection of streptozotocin. After modeling, irbesartan treatment and TWP treatment groups received an intragastric injection of corresponding drugs. The body weights were recorded and the 24 h Pro quantitative levels detected at Weeks 4, 8, 12 and 16 respectively. After sacrificing at Week 16, serum creatinine (Scr) was detected. The renal tissues were excised and examined after HE and PAS staining. The expressions of Act-A, alpha-smooth muscle actin (α-SMA), collagen type Ⅳ (Co-Ⅳ) and E-cad in renal tubulointerstitium were detected by immunohistochemistry. And the expressions of Act-A, α-SMA, Co-Ⅳ and mRNA of E-cad in renal tissue were detected by real-time quantitative fluorescent polymerase chain reaction (PCR).

Compared with DN model group, 24 hPro((67.1±9.6), (61.8±8.0) vs (158.3±13.3)mg), quantitative Scr ((31.7±4.1), (32.6±6.2)vs(55.3±8.9)μmol/L) and renal hypertrophic index((9.14±0.65), (7.50±0.34) vs (11.28±0.70)mg/g) of irbesartan treatment and TWP treatment groups decreased obviously at Week 16 (allP<0.05). However, no statistical significance existed between irbesartan treatment and TWP treatment groups. The body weights of irbesartan treatment and TWP treatment groups increased versus DN model group. Pathological sections showed that lesion degree of renal tubulointerstitium became alleviated in each group. Yet no statistical significance existed between irbesartan treatment and TWP treatment groups. Both immunohistochemistry and real-time quantitative fluorescent PCR showed that the expressions of Act-A, α-SMA and Co-Ⅳ significantly decreased in renal tubulointerstitium (P<0.01) while the expression E-cad significantly increased (P<0.01) in inirbesartan treatment and TWP treatment groups versus DN model group. And no statistical significance existed between irbesartan treatment and TWP treatment groups.

TWP may down-regulate the expression of Act-A and inhibit the transdifferentiation of renal tubulointerstitial so as to delay renal fibrosis.

To explore the effects of AS1411 on the apoptosis of taxol-resistant lung adenocarinoma A549 cell (A549/T cell).

A549/T cells were treated with AS1411 at a concentration gradient of 0-20.0 μmol/L. The assays of methyl tolyl sulfide (MTS) and colony formation were used to detect the cellular vitality (absorbance value ( A_{490 nm})) and proliferation. The apoptotic effects were detected by flow cytometer and the relevant apoptotic signaling proteins detected by Western blot.

A549/T cells exhibited some characteristics of epithelial mesenchymal transition (EMT) and a negative expression of epidermal growth factor receptor (EGFR). After a treatment of 5.0 μmol/L AS1411, compared to the control sequence, cell vitality was inhibited ( A_{490 nm:}0.185±0.009 vs 0.272±0.006, P<0.001) and the number of clone formation decreased (74±13 vs 120±12,P=0.010). With rising AS1411 concentration, A549/T cells vitality decreased in a dose-dependent manner. After a 48-hour treatment of 20.0 μmol/L AS1411, the ratio of apoptosis ((19.9±2.6)%) had significant difference ( P=0.002) with the control sequence group ((8.8±1.3)%). Compared to the control sequence group, the expressions of protein kinase B (AKT), extracellular regulated protein kinases 1/2 (ERK1/2) and B-cell lymphoma 2 (Bcl-2) protein declined (0.353±0.003, 0.432±0.015, 0.294±0.015 vs 0.688±0.003, 0.911±0.019, 0.422±0.018, all P<0.001).

AS1411 may induce the apoptosis of A549/T cells through inhibiting the AKT-ERK pathways.

Gastrointestinal motility disorder is one of the important pathophysiological mechanisms associated with gastrointestinal symptoms in functional gastrointestinal diseases and even organic diseases^[1,2]It is also a therapeutic entry point to eliminate or relieve gastrointestinal symptoms. However, the clinical thinking and strategy of targeting gastrointestinal motility disorders to treat functional gastrointestinal diseases have always encountered the embarrassing situation of unsatisfactory efficacy. The reasons for this situation are as follows: (1) The forms of gastrointestinal motility disorders are complex and diverse, and there is no correspondence between them and clinical symptoms^[3,4]； (2) The efficacy of gastrointestinal motility promoting drugs has not been completely defined, especially the understanding of individualized response to gastrointestinal motility of patients is still lacking^[5]； (3) The etiology of gastrointestinal motility disorders is complex, and the overall efficacy of gastrointestinal motility-promoting drugs is not ideal^[5,6]。 Therefore, therapeutic ideas other than gastrointestinal motility-promoting drugs deserve attention. Now we will elaborate on the above three aspects.

Antibody-related autoimmune diseases refer to diseases that cause abnormal B lymphocyte function to produce autoantibodies and then mediate tissue damage for various reasons, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), autoimmune hemolytic anemia (AIHA), idiopathic thrombocytopenia (ITP), etc. Studies have shown that B lymphocyte immune memory is closely related to the occurrence, development, recurrence and prognosis of such diseases. B lymphocyte immune memory is mainly mediated by memory B lymphocytes (Bm) and long-lived plasma cells.

A cough lasting more than 8 weeks is called a chronic cough^[1]。 Chronic cough is one of the most common diseases in respiratory clinic, which can seriously interfere with patients' sleep and become an important reason for patients to seek treatment. Common causes of chronic cough that are easily overlooked include the coexistence of one or more of gastroesophageal reflux disease (GERD), upper airway cough syndrome (UACS), and cough variant asthma (CVA)^[2]Some patients still have no significant improvement in symptoms after treatment for the above diseases^[3]。 Recent studies suggest that sleep apnea hypopnea syndrome (SAHS) may be an important cause of unexplained cough, but this has not been included in the newly published guidelines for cough diagnosis and treatment^[4,5]。