Construction of clinical comprehensive evaluation index system of anti-lung cancer drugs and empirical study / 中国药房

OBJECTIVE To construct a comprehensive evaluation index system for anti-lung cancer drugs， and to provide a basis for drug selection and rational clinical use. METHODS Based on the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs （2021 edition for trial use）， a preliminary evaluation index system framework and an index preselection pool were initially formulated through literature analysis. The evaluation indices were then selected and modified by using the Delphi method. The weights of each index were determined through expert scoring and relevant calculations， thereby establishing a comprehensive evaluation index system for anti-lung cancer drugs. Referred to Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions， scoring detailed rules for clinical comprehensive evaluation indexes of anti-lung cancer drugs were formulated. The constructed comprehensive evaluation index system and scoring detailed rules were applied to conduct empirical evaluation of the anti-lung cancer drug pembrolizumab. RESULTS The constructed comprehensive evaluation index system for anti-lung cancer drugs included 6 primary indicators and 15 secondary indicators. The weights of the primary indicators were as follows： safety （18）， efficacy （38）， economy （15）， innovation （9）， suitability （10）， and accessibility （10）. The scoring detailed rules for the comprehensive evaluation index system for anti-lung cancer drugs had been preliminarily established. The results of empirical evaluation showed that the comprehensive evaluation score （61 points） of pembrolizumab combined with chemotherapy regimen was higher than that of the monotherapy chemotherapy regimen （56 points）. The former demonstrated superior efficacy， innovation and suitability compared to the latter， while the latter exhibited better safety and economy. CONCLUSIONS The constructed comprehensive evaluation index system for anti-lung cancer drugs has the potential for generalizability and practical application， providing a reference basis for rational clinical drug use.

Jiaotaiwan increased GABA level in brain and serum, improved sleep via increasing NREM sleep and REM sleep, and its component identification.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiaotaiwan (JTW) is good at communicating the heart and kidney. That meets the main mechanism of insomnia in traditional Chinese medicine. But the mechanism of JTW in promoting sleep is not clear. AIM OF THE STUDY: To investigate the mechanism of JTW in promoting sleep and identify the main components. MATERIALS AND METHODS: In this study, we detected the levels of GABA in serum and brain via LC-MS/MS analysis and investigated the hypnotic effect of JTW and its role in promoting sleep via Sleep monitoring and vigilance state analysis. Further, the identification of the main components was carried out by using LC-MS/MS analysis. RESULTS: JTW could increase the GABA levels in serum, FC and BS of SDM rats. JTW reduced the amount of wakefulness, increased the time of NREM sleep and REM sleep. A total of 25 compounds were identified. CONCLUSIONS: The current work provides valuable information on the hypnotic effects of JTW and its regulatory mechanisms in promoting sleep.

Isolation, identification and biological characteristics of rat bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND: How to effectively harvest bone marrow mesenchymal stem cells with homogeneity is crucial for cartilage tissue engineering research. OBJECTIVE: To isolate and culture rat bone marrow mesenchymal stem cells and to observe biological characteristics of the cells. METHODS: Bone marrow mesenchymal stem cells were isolated from the femur and tibia of 30 Sprague-Dawley rats using the whole bone marrow adhesion method. Cell surface markers were identified using flow cytometry, cell proliferation ability was observed through cell counting, and cell survival rate was determined by MTT assay. RESULTS AND CONCLUSION: The harvested cells were mostly round and oval, which partially showed a triangular shape. Cell fusion appeared after 12-15 days of inoculation. The proliferation of passaged cells was accelerated. Two hours after passage, the cells evenly covered the bottom of the culture dish. With the increasing of cell generations, the cell proliferation ability was gradually decreased. The survival rates of cells at passages 1-5 were over 95%, significantly higher than those at passages 6 and 7 (P < 0.05). The harvested cells were negative for CD34, but positive for CD44. To conclude, the whole bone marrow adhesion method is effective to isolate rat bone marrow mesenchymal stem cells with stable growth and strong proliferation ability. Passage 5 cells can be selected as seed cells for cartilage tissue engineering.

Preventive effects of Haishe capsules on the conversion of amnestic mild cognitive impairment to Alzheimer's disease / 中华老年医学杂志

Objective To evaluate the preventive effects of Haishe capsules on the conversion of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease(AD).Methods Patients (n=120) with aMCI from our department were recruited and randomly divided into the treatment group and the control group (n=60 in each group).The treatment group was given 0.9 gram of Haishe capsules three times a day while the control group received no drug treatment.Data on the conversion ratio,memory and cognitive function were comparedbetween the groups in a 24-months follow-up.Results By the end of the study,12 patients in the treatment group and 15 in the control group dropped out.Valid data for 93 patients were available for statistical analysis (48 in the treatment group and 45 in the control group).The number of aMCI patients who converted to AD was 6,with a conversion ratio of 12.5％ (6/48);and the number of patients who went through conversion in the control group was 13,with a conversion ratio of 28.8％ (13/45).The difference in conversion between the two groups was statistically significant (x2 =3.83,P＜0.05).After 24 months,MMSE scores for the treatment group (25.52± 1.07) had no significant change compared with baseline levels,while MMSE scores for the control group decreased significantly(24.75--1.49) and were markedly lower than thosefor the treatment group (t=2.85,P＜0.05).MoCA scores for the treatment group (19.39 ±2.01) did not show decline until the end of the study,while those for the control group started to decrease about half way through the study and were lower than scores for the treatment group (t =2.41,P＜0.05).Compared with baseline levels,ADAS-Cogscores for the treatment group (7.62± 1.06) did not increase significantly during the course of the study.ADAS-Cogscores forthe control group were higher at both half way (7.70±0.75) and the end of the study (8.18±0.80)than base line levels,and there was a statistically significant difference in end-of-study ADAS-Cog scores between the two groups(t =-2.6,P＜ 0.05).Conclusions Haishe capsules not only effectively maintain memory and cognitive function,but also delay the conversion from aMCI to AD.

Effects of cannabinoid HU210 on experimental acute pancreatitis and possible relationship with Toll-like receptor 4 signaling pathway / 中国病理生理杂志

AIM:Using Toll-like receptor 4 gene knockout (tlr4-/-) mice and the wild-type (WT) mice with the same C57BL/10J genetic background, the effects of HU210, a cannabis preparation, on caerulein (CAE)-induced acute pancreatitis (AP) and the potential mechanisms were investigated.METHODS:WT or tlr4-/-mice were randomly divided into AP group, AP+HU210 group and control group.AP was induced by intraperitoneal injection of CAE (50 μg·kg-1·h-1) for a total of 6 times and lipopolysaccharide (LPS) at 10 mg/kg 6 h after the first injection of CAE.HU210 (50 μg/kg) was given 30 min before and 4 h after the first injection of CAE in AP+HU210 group.The animals in control group were given normal saline instead of CAE and LPS in the same way.The mice were sacrificed 3 h after the last injection.The blood, the pancreas, the lungs and the intestinal Peyer's patches were harvested.RESULTS:Compared with control group, the pancreatic pathological score and P38 protein expression, plasma amylase activity and inflammatory mediator levels, and lung MPO activity were significant increased (P<0.05) in both WT and tlr4-/-mice with AP.Compared with the WT mice with AP, the tlr4-/-mice with AP showed significantly low levels of IL-6, TNF-α and MCP-1 in the plasma, low expression levels of pancreatic P38 and p-P38 protein (P<0.05), and mild alterations of CD3+ T-lymphocytes, CD4+ T-lymphocytes and the ratio of CD4+/CD8+ (P<0.05).The administration of HU210 attenuated the pancreatic pathological changes and the lung MPO activity in both stains of mice with AP (P<0.05).However, the inhi-bitory effects of HU210 on the increased amylase activity in the plasma and the increased protein levels of pancreatic P38 and p-P38 were remarkable (P<0.05) in WT mice instead of in tlr4-/-mice.CONCLUSION:TLR4 is mainly involved in AP-related systemic inflammatory response and its mechanism may be dependent on TLR4-P38 MAPK signaling pathway.The intervention of HU210 in AP plays a protective role mainly by inhibiting the infiltration of inflammatory cells, and the relationship with TLR4 signaling pathway is not obvious.

Surveillance of antimicrobial resistance in the bacterial strains isolated from hospitals in Dongguan, Guangdong Province: 2015 report / 中国感染与化疗杂志

Objective To survey the resistance profile of clinical isolates to antibiotics across the hospitals in Dongguan,Guangdong Province during 2015.Methods Kirby-Bauer method or automated system was used to test the susceptibility of clinical isolates to selected antimicrobial agents.Results were analyzed according to CLSI 2015 breakpoints.The susceptibility data were analyzed using WHONET 5.6 software.Results A total of 29 665 strains of microorganisms were isolated,of which gram positive cocci accounted for 32.1％ (9 509/29 665) and gram negative bacilli accounted for 67.9％ (20 156/29 665),respectively.The prevalence of methicillinresistant Staphylococcus was 23.3％ (705/3 024) in S.aureus and 43.6％ (1 054/2 419) in coagulase-negative Staphylococcus.No vancomycin-resistant staphylococcal strain was found.ESBLs-producing strains accounted for 36.4％ (2 554/7 020) in E.coli and 24.5％(792/3 227) in Klebsiella isolates.The prevalence of carbapenem-resistant Enterobacteriaceae was 0.2％ (30/13 077).The prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) was 16.0％ (500/3 116) and 53.9％ (827/1 533),respectively.The prevalence of penicillin-resistant S.pneumoniae (PRSP) strains was 10.1％ (142/1 404).Beta-lactamase was produced in 30.6％ (276/902) of the H.influenzae strains.The prevalence of vancomycin-resistant Enterococcus (VRE) strains was 0.7％ (10/1 441).Conclusions Periodic surveillance of antimicrobial resistance is valuable for rational antimicrobial therapy,formulation of treatment guidelines and infection control and prevention measures,as well as preventing the spread of drug-resistant strains.

Chinese herbal preparation Qing Yi TangⅡgranule protects against ex-perimental acute pancreatitis in mice / 中国病理生理杂志

[ ABSTRACT ] AIM: To investigate the protect effect of Chinese herbal preparation, Qing Yi TangⅡgranule (QYT), on acute pancreatitis (AP) mice and its mechanism.METHODS:Adult male and female C57BL/6 mice (n=24) were randomly divided into control group, AP group and AP+QYT group.Severe AP was induced by combined intra-peritoneal injection of caerulein (50μg/kg) and lipopolysaccharide (LPS;10 mg/kg).Drinking water or 24%QYT solu-tion was given to the mice in AP group or AP+QYT group by oral gavage.The mice in control group were intraperitoneally injected with equivalent volume of normal saline and gavaged with water.The mice were sacrificed 3 h after the last injec-tion.Severity of AP was assessed by biochemical markers and histology.The plasma level of IL-6 and MCP-1, and lung myeloperoxidase ( MPO) levels were determined for assessing the extent of systemic inflammatory response.The intestinal microflora, T lymphocytes and T-lymphocyte subgroups were examined for assessing the function of the intestinal barrier. RESULTS:Compared with control group, the mice in AP group presented significant increases in pathological histological scores, plasma amylase activity and IL-6 and MCP-1 levels, as well as the MPO activity in the lung and pancreatic tissues. QYT attenuated these changes to some extent.Furthermore, the increased intestinal microflora was significantly reversed by QYT.No difference of the numbers of Peyer’ s patches in small intestine in the 3 groups was observed, but the percentage of CD3 +T lymphocytes decreased significantly in AP group, and increased percentage of CD4 +and CD4 +/CD8 +ratio were found in AP group and AP+QYT group.CONCLUSION: QYT protects against cearulein and LPS-induced acute pancreatitis in mice.The mechanisms may be related to the suppression of the inflammatory response, promoting intestinal bacteria removal, and regulating the functions of T lymphocytes in the intestinal barrier.

A meta-analysis of 5-aminosalicylic acid preventing the development of in-testinal neoplasia in inflammatory bowel disease / 中国病理生理杂志

AIM:We conducted an evaluation of clinical data with meta analysis to investigate the preventive effect of 5-aminosalicylic acid (5-ASA) on inflammatory bowel disease ( IBD)-associated colorectal cancer ( CRC) or dys-plasia (Dys) (IBD-CRC/Dys).METHODS: The information was retrieved from the main databases such as PubMed, Web of Science, the Cochrane Library, etc.All full-text articles about the prevention of IBD-CRC/Dys by 5-ASA were in-cluded if they conformed to the standards.The odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. According to the types of IBD and the treatment course, the subgroup analysis was conducted, respectively.RESULTS:Fifteen articles were selected, including 5 038 IBD patients.Pooled analysis showed a protective association between 5-ASA and IBD-CRC/Dys (OR=0.53, 95%CI:0.37~0.76).Among them, both ulcerative colitis patients (OR=0.45, 95%CI:0.27~0.77) and Crohn disease patients ( OR=0.39, 95% CI:0.16~0.97) with 5-ASA therapy were less likely to develop CRC/Dys compared with those without 5-ASA treatment.5-ASA treatment for 1~20 years shows a pre-ventive benefit (OR=0.43, 95%CI:0.25~0.74).However, a minimum 5-ASA exposure of 2~6 months did not show a preventive benefit (OR=0.59, 95%CI:0.26~1.34).CONCLUSION:5-ASA protects against CRC/Dys in IBD pa-tients.Additionally, the protective effect is treatment time dependent.Treatment course for 1~20 years shows an evident preventive benefit.

Visual function and morphological changes in the macular area of patients with type 2 diabetes mellitus after intensive insulin therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intensive insulin therapy has been found to lessen the progress of diabetic retinopathy (DR) to some extent, while it has also been implicated to be responsible for decrease of DR. We investigated visual function and morphological changes in the macular area in short-term follow-up of patients with type 2 diabetes mellitus after intensive insulin therapy.</p><p><b>METHODS</b>This was a prospective clinical study of nonproliferative DR patients (102 eyes, 120 patients) undergoing intensive insulin therapy. The Contrast Glare Tester (Takagi CGT-1000) was used to examine contrast sensitivity (CS) and Heidelberg Retina Tomograph (HRT) II and Stratus Model 3000 OCT were used to observe the changes of morphology in the macular area. Follow-up times were pre-intensive therapy, 3 and 6 months post-intensive therapy.</p><p><b>RESULTS</b>CS at low and middle frequencies was higher at 3 and 6 months post-therapy compared with pre-therapy (P < 0.05). Significant differences in CS at low frequency were found between 6 and 3 months post-therapy (P < 0.05). Macular edema index was lower in the first, second, and third rings of the macular area after intensive therapy compared with pre-therapy (P < 0.05). Compared with 3 months post-therapy, the macular edema index was lower in the first, second, and third rings of the macular area at 6 months post-therapy (P > 0.05). No significant differences in the thickness of the first, second, and third rings of the macular area were detected between 3 and 6 months post-therapy and pre-therapy (P > 0.05).</p><p><b>CONCLUSION</b>CS and macular edema indexes were significantly improved in nonproliferative diabetic retinopathy patients after intensive insulin therapy, but thickness of the macular area was unchanged.</p>