Exploration of potential active ingredients and mechanism of action of Xihuang pill-medicated serum against glioma based on HPLC-Q-TOF-MS/MS, network pharmacology and experimental verification / 药学学报

Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC50 of 30.96 μmol·L-1, and KBA (30 μmol·L-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

Comparison of short-term efficacy of neoadjuvant immunotherapy combined with chemotherapy and neoadjuvant chemoradiation for locally advanced resectable esophageal squamous cell carcinoma / 中国胸心血管外科临床杂志

@#Objective    To investigate the short-term therapeutic effect of neoadjuvant immunotherapy combined with chemotherapy in the locally advanced esophageal squamous cell carcinoma. Methods    The clinical data of patients with esophageal squamous cell carcinoma treated with neoadjuvant treatment in Gaozhou People's Hospital from August 2019 to October 2020 were retrospectively analyzed. According to the different treatments, the patients were divided into two groups: a neoadjuvant immunotherapy combined with chemotherapy group (NIC group) and a neoadjuvant chemoradiotherapy group (NC group). The baseline data, incidence of adverse events during treatment, perioperative indicators, postoperative pathological remission rate and incidence of postoperative complications were compared between the two groups. Results    Totally 33 patients were enrolled, including 15 males and 18 females, with an average age of 62.37±7.99 years. There were 17 patients in the NIC group and 16 patients in the NC group. In the NIC group, the carcinoma was mainly located in the middle and lower esophagus, with 5 paitents in stage Ⅱ, 9 patients in stage Ⅲ, and 3 patients in stage Ⅳa. In the NC group, the carcinoma was mainly located in the upper-middle esophagus, with 1 patient in stage Ⅱ and 15 patients in stage Ⅲ. During the neoadjuvant treatment, there was no significant difference in the occurrence of bone marrow suppression or gastrointestinal reactions between the two groups (P>0.05). There were 4 immune-related rashes in the NIC group and 1 esophageal perforation in the NC group. Fourteen (82.35%) patients in the NIC group and 12 (75.00%) patients in the NC group completed the operation on schedule. The postoperative ICU stay time and chest tube indwelling time in the NIC group were shorter than those in the NC group (P<0.05). There were 5 patients of complete remission in the NIC group, and 6 patients in the NC group. There was no significant difference in the pathological regression grade or residual tumor cells between the two groups (P>0.05). There was no significant difference in the incidence of anastomotic fistula, thoracic gastric fistula, bronchial mediastinal fistula, abdominal distension, pulmonary infection, stroke, or hoarseness during the perioperative period between the two groups of patients who completed the operation (P>0.05). In the NC group, 2 patients died during the perioperative period because of thoracic gastric fistula complicated by severe infection. Conclusion    Neoadjuvant immunotherapy combined with chemotherapy dose not significantly increase the occurrence of adverse events and shows a good rate of pathological remission, which indicates that the neoadjuvant immunotherapy combined with chemotherapy is a safe, feasible and potential new treatment model.

Analysis of influencing factors of multi-site musculoskeletal disorders among workers in the chemical pharmaceutical industry / 中国职业医学

{L-End}Objective To analyze the prevalence of multi-site work-related musculoskeletal disorders (WMSDs) and their influencing factors among workers in the chemical pharmaceutical industry. {L-End}Methods A total of 563 workers from three chemical pharmaceutical factories in Guangzhou City were selected as the research subjects using the judgment sampling method. The prevalence of multi-site WMSDs in the past 12 months was investigated using the electronic questionnaire of Chinese Version of Musculoskeletal Disorders Questionnaire. {L-End}Results The prevalence of multi-site WMSDs in the research subjects was 30.0% (169/563). The results of multivariable logistic regression analysis showed that workers who smoked regularly/frequently and those who had their hands above shoulder level for long periods of time had a lower risk of multi-site WMSDs than those who never/occasionally smoked (all P≤0.05). Workers with a high school, secondary specialty, college degree, or above had a lower risk of multi-site WMSDs than those with a middle school education or below (all P<0.05). The longer the daily working hours, the higher the risk of multiple WMSDs (all P<0.05). Workers with regular/frequently work shifts had a lower risk of multi-site WMSDs than those with none/occasional work shifts (P<0.05). {L-End}Conclusion The prevalence of multi-site WMSDs among workers in the chemical pharmaceutical industry is relatively high. The influencing factors are individual factors, unreasonable work organization and poor ergonomics factors.

Prevalence and influencing factors of work-related musculoskeletal disorders among workers in chemical pharmaceutical industry / 环境与职业医学

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems in the world. Pharmaceutical industry is an important part of China's national economy. At present, there are few related studies reported at home and abroad. Objective To investigate the status and influencing factors of WMSDs in chemical pharmaceutical industry. Methods A cross-sectional epidemiological survey was conducted among all workers from three chemical pharmaceutical enterprises in Guangzhou. The Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, symptoms of musculoskeletal disorders, types of work, work organization, and and work postures. Multiple logistic regression method was used to analyze the risk factors of WMSDs in chemical pharmaceutical workers. Results In this study, 563 workers were selected as subjects. The total prevalence rate of WMSDs symptoms in the chemical pharmaceutical workers was 43.9% (247/563), and the leading body part-specific prevalence rate from high to low was 34.3% in the lower back, 24.3% in the upper back, 24.0% in the shoulders, and 23.8% in the neck. The prevalence rate of WMSDs symptoms in multiple body parts (30.0%) was 2.16 times higher than that in single body part (13.9%), and the prevalence rate of WMSDs symptoms in four body parts was the highest (11.4%). The results of multiple logistic regression analysis showed that age ≥50 years (reference age <30 years) (OR=2.140, 95%CI: 1.054-4.345), often or very often (reference never/rarely) long-time head rotating (OR=2.695, 95%CI: 1.753-4.142) and long-time keeping arms above shoulders (OR=1.902, 95%CI: 1.108-3.265) increased the risk of reporting WMSDs symptoms (P<0.05). Regarding education level, workers with high school and technical secondary school (OR=0.333, 95%CI: 0.175-0.636) or college and above (OR=0.413, 95%CI: 0.216-0.790) education had a lower risk of reporting WMSDs symptoms than those with middle school or below (P<0.05). Conclusion The prevalence rate of reporting WMSDs symptoms in chemical pharmaceutical industry is high, the involving body parts are lower back, upper back, shoulders, and neck, and reporting simultaneous occurrence of WMSDs symptoms in multiple body parts is common. The chemical pharmaceutical manufacturers can reduce the risk of WMSDs by strengthening the training on workers' ergonomics knowledge, paying attention to the less educated personnel, protecting the elderly workers, and avoiding awkward work postures, like rotating head for a long time and raising arms over shoulders.

The effect and mechanism of Xihuang pill inhibits the formation of vasculogenic mimicry in human glioblastoma cells by down-regulating HIF-1α/VEGFA/VEGFR2 signaling pathway / 药学学报

Our studies were aimed to explore the effect and mechanism of the inhibition of the formation of vasculogenic mimicry (VM) in human glioblastoma cells by Xihuang pill (XHP) medicated serum through regulating the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. The medicated serum of XHP was prepared by gavage for 7 days to male SD rats (approval number of animal experiment ethics: 202105A051). The hypoxia model of U251 cells was established using 200 μmol·L-1 of CoCl2. After treatment with XHP-medicated serum, cell viability and proliferation of U251 cells were detected by CCK-8 and cell cloning experiment. Cell apoptosis and cell cycle of U251 cells were determined by flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell invasion assay. The formation of VM was assessed by three-dimensional cell culture of U251 cells. The protein expression levels of HIF-1α, VEGFA, VEGFR2, phosphorylated-VEGFR2 (p-VEGFR2), vascular endothelial-cadherin (VE-cadherin), Eph receptor tyrosine kinases A2 (EphA2), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 14 (MMP14) and laminin γ2 in U251 cells were detected by Western blot. The results showed that 10% XHP-medicated serum had little effect on the cell viability, proliferation, apoptosis and cell cycle of U251 cells under hypoxia. Compared with the model group, 10% XHP-medicated serum at 1.0, 1.5 and 2.0 h significantly decreased the migration rate (P < 0.01) and the number of invading U251 cells (P < 0.01). 10% XHP-medicated serum at 2.0 h significantly suppressed the formation of VM tubular structures in U251 cells under the condition of hypoxia (P < 0.01). Western blot experiment showed that 10% XHP-medicated serum significantly down-regulated the expression of HIF-1α, VEGFA, phospho-VEGFR2, VE-cadherin, EphA2 and MMP14 proteins (P < 0.05). In conclusion, XHP could inhibit the formation of VM in human glioblastoma U251 cells to suppress the angiogenesis by down-regulating the HIF-1α/VEGFA/VEGFR2 signaling pathway.

Application of event-related potential P300 in the evaluation of cognitive dysfunction in patients with traumatic brain injury / 四川精神卫生

ObjectiveTo explore the application value of event-related potential P300 in the evaluation of cognitive dysfunction in patients with traumatic brain injury. MethodsFrom January to September 2021， a total of 36 patients with traumatic brain injury who were conservatively treated in the Neurosurgery Department of the Third Hospital of Mianyang and met the diagnostic criteria were selected as the experimental group. And 36 participants were recruited from the family members and carers of other patients in the hospital as the control group. Oddball paradigm was used to measure the event-related potential P300. Montreal Cognitive Assessment （MoCA） and Mini-Mental State Examination （MMSE） were used to assess the cognitive function of the subjects. The latency and amplitude of P300， MoCA and MMSE scores were compared between two groups. The detection rates of P300 latency， MoCA and MMSE on cognitive dysfunction in patients with traumatic brain injury were compared. ResultsMoCA and MMSE scores in experimental group were lower than those in control group ［（18.08±4.29） vs. （27.36±1.20）， （22.53±3.54） vs. （28.11±1.09）， t=-12.510， -9.041， P<0.05］. The latency of P300 in experimental group was higher than that in control group ［（406.08±26.95）ms vs. （367.08±22.50）ms， t=6.665， P<0.05］， and the amplitude was lower than that in control group ［（7.76±0.90）μV vs.（9.87±0.99）μV， t=-9.459， P<0.05］. In experimental group， the positive detective rate of P300 latency and MoCA on cognitive dysfunction were higher than that in MMSE （χ2=5.675， 7.604， P<0.05）. ConclusionEvent-related potential P300 can be used as an objective clinical indicator for evaluating cognitive dysfunction in patients with traumatic brain injury.

Development of a surface plasmon resonance biosensor for accurate and sensitive quantitation of small molecules in blood samples / 药物分析学报

Therapeutic drug monitoring(TDM)has played an important role in clinical medicine for precise dosing.Currently,chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy.However,some problems still exist in practical appli-cations,such as complicated operation and the influence of endogenous substances.Surface plasmon resonance(SPR)has been applied to detect the concentrations of small molecules,including pesticide residues in crops and antibiotics in milk,which indicates its potential for in vivo drug detection.In this study,a new SPR-based biosensor for detecting chloramphenicol(CAP)in blood samples was developed and validated using methodological verification,including precision,accuracy,matrix effect,and extraction recovery rate,and compared with the classic ultra-performance liquid chromatography-ultraviolet(UPLC-UV)method.The detection range of SPR was 0.1-50 ng/mL and the limit of detec-tion was 0.099±0.023 ng/mL,which was lower than that of UPLC-UV.The intra-day and inter-day ac-curacies of SPR were 98％-114％and 110％-122％,which met the analysis requirement.The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples;moreover,the SPR biosensor has better sensitivity.Therefore,the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.

Z-guggulsterone reversed multi-drug resistance of hepatocarcinoma chemotherapy through down-regulating a PXR/P-gp pathway / 中国药理学通报

Aim To investigate the improved effects of Z-guggulsterone on the chemotherapy agents-induced proliferation and apoptosis through regulating PXR(pregnane X receptor)/P-gp(P-glycoprotein)signaling pathway in human hepatocellular carcinoma cells.Methods HepG2 cells were treated with Z-guggulsterone, DDP(cis-platinum)and 5-FU(5-fluorouracil)alone or in combination.CCK-8(Cell Counting Kit-8), Annexin-FITC/PI(Annexin V-fluorescein isothiocyanate isomer/propidium iodide)flow cytometry, RT-qPCR(Real-time quantitively Polymerase Chain Reaction)and Western blot were used to determine cell proliferation, apoptosis, the expression of MDR1 mRNA, PXR and P-gp respectively.Results Compared to DDP or 5-FU treatment alone, Z-guggulsterone(30 μmol·L-1)enhanced the inhibitory effects of DDP or 5-FU on the proliferation and apoptosis of HepG2 cells.Z-guggulsterone(30 μmol·L-1)also significantly reduced the expression levels of PXR,P-gp and MDR1 mRNA in HepG2 cells.Further research demonstrated that rifampicin, one agonist of PXR, increased the expression of PXR and P-gp, while Z-guggulsterone reversed its effects.Meanwhile, the expressions of PXR and P-gp were reduced by ketoconazole, one antagonist of PXR, and further decreased by co-administration with Z-guggulsterone.Conclusion Z-guggulsterone can improve the effects of chemotherapy on the proliferation and apoptosis of hepatocellular carcinoma cell lines by down-regulating the PXR/P-gp signaling pathway.

Epidemiological characteristics and treatment outcome analysis of 229 patients with hydrofluoric acid burns in hands / 中华烧伤杂志

Objective: To explore the epidemiological characteristics and treatment outcomes of patients with hydrofluoric acid burns in hands. Methods: A retrospective observational study was conducted. The medical records of 229 patients with hydrofluoric acid burns in hands who were admitted to Zhejiang Quhua Hospital from January 2008 to December 2020 and met the inclusion criteria were collected. The following statistical data of patients were collected, including gender, age, type of affiliated enterprise, hydrofluoric acid mass fraction, injury site, total burn area, prehospital time, length of hospital stay, length of wound healing, whether hypocalcemia and hypomagnesemia occurred or not on admission, whether surgery intervention was performed or not, and whether scar sequelae occurred or not. Single factor and multivariate logistic regression analysis were used to screen out the risk factors impacting surgery intervention and scar sequelae of all the patients and patients whose hydrofluoric acid mass fraction was known. Single factor and multivariate linear regression analysis were used to screen out the risk factors impacting the length of wound healing of all the patients and patients whose hydrofluoric acid mass fraction was known. Results: The 229 patients included 206 males and 23 females, with the majority aged 30 to 50 years (139 patients). The type of affiliated enterprise of majority patients was non-fluorine chemical enterprise. The hydrofluoric acid mass fraction was known in only 91 patients, mainly medium. The majority injury site was in the middle and end of finger. The total burn area was below or equal to 1% total body surface area. The prehospital time was 19 (9, 29) h. The length of hospital stay was 2 (1, 7) d. The length of wound healing was 12 (8, 18) d. The proportions of hypocalcemia and hypomagnesemia were 0.9% (2/229) and 1.3% (3/229) on admission, respectively. Thirty-six patients had surgeries and 83 patients had scar sequelae. In 229 patients, single factor logistic regression analysis showed that both type of affiliated enterprise and prehospital time were the factors impacting surgery intervention (with odds ratio values of 7.86 and 51.35, respectively, 95% confidence intervals of 1.83-33.76 and 11.89-221.78, respectively, P<0.01) and scar sequelae of patients (with odds ratio values of 3.62 and 27.40, respectively, 95% confidence intervals of 1.76-7.43 and 13.25-56.68, respectively, P<0.01); multivariate logistic regression analysis showed that prehospital time was the independent risks factor impacting surgery intervention and scar sequelae of patients (with odds ratio values of 43.00 and 24.55, respectively, 95% confidence intervals of 9.89-187.03 and 11.78-51.16, respectively, P<0.01); single factor linear regression analysis showed that both type of affiliated enterprise and prehospital time were the factors impacting the length of wound healing of patients (with β values of 6.16 and 12.83, respectively, 95% confidence intervals of 3.38-8.93 and 10.72-14.93, respectively, P<0.01); multivariate linear regression analysis showed that both type of affiliated enterprise and prehospital time were the independent risk factors impacting the length of wound healing of patients (with β values of 2.81 and 12.16, respectively, 95% confidence intervals of 0.50-5.13 and 10.00-14.31, respectively, P<0.05 or P<0.01). In 91 patients whose hydrofluoric acid mass fraction was known, single factor logistic regression analysis showed that type of affiliated enterprise, hydrofluoric acid mass fraction (low and high), and prehospital time were all the factors impacting surgery intervention of patients (with odds ratio values of 9.10, 11.25, 10.69, and 0.04, respectively, 95% confidence intervals of 1.15-72.25, 1.39-90.93, 1.32-86.59, and 0.01-0.19, respectively, P<0.05 or P<0.01), type of affiliated enterprise, hydrofluoric acid mass fraction, and prehospital time were all the factors impacting scar sequelae of patients (with odds ratio values of 0.32, 0.21, and 36.80, respectively, 95% confidence intervals of 0.11-0.92, 0.06-0.73, and 11.03-122.79, respectively, P<0.05 or P<0.01); multivariate logistic regression analysis showed that both hydrofluoric acid mass fraction and prehospital time were the independent risk factors impacting surgery intervention of patients (with odds ratio values of 11.51 and 0.04, respectively, 95% confidence intervals of 1.22-108.26 and 0.01-0.25, respectively, P<0.05 or P<0.01), prehospital time was the independent risk factor impacting scar sequelae of patients (odds ratio=37.71, with 95% confidence interval of 9.97-142.69, P<0.01); single factor linear regression analysis showed that type of affiliated enterprise, hydrofluoric acid mass fraction (low and high), and prehospital time were all the factors impacting the length of wound healing of patients (with β values of 7.12, -5.63, -9.74, and 13.50, respectively, 95% confidence intervals of 2.43-11.81, -10.59--0.68, -14.78--4.70, and 10.14-16.86, respectively, P<0.05 or P<0.01); multivariate linear regression analysis showed that both hydrofluoric acid mass fraction and prehospital time were the independent risk factors impacting the length of wound healing of patients (with β values of -5.84 and 0.09, respectively, 95% confidence intervals of -10.59--1.08 and 0.05-0.12, respectively, P<0.05 or P<0.01). Conclusions: The majority of patients with hydrofluoric acid burns in hands are young and middle-aged males. Type of affiliated enterprise, hydrofluoric acid mass fraction and prehospital time are the risk factors that affect the treatment outcomes of patients with hydrofluoric acid burns in hands.

Study on epidemiological status of e-cigarette use among adolescent in Zhejiang province, China / 中华流行病学杂志

Objective: To describe the prevalence of e-cigarette use among adolescent in Zhejiang province, and to analyze its distribution of different genders and school types to provide evidence for controlling the use of e-cigarette among adolescent. Methods: A total of 7 663 students from 60 middle schools through stratified multi-stage cluster sampling methods from Zhejiang province were surveyed by using questionnaire. Indicators as tried to use e-cigarette rate, current e-cigarette using rate, and other indicators were collected. All data were weighted by age proportions of adolescent in Zhejiang. Results: The prevalence of tried to use and current using e-cigarettes among middle school students were 6.99% and 1.45%, respectively; and there were 4.19% juniors who were susceptibility to future e-cigarette use. The rate of tied to use e-cigarette, current using e-cigarette and susceptibility to future e-cigarette use were higher in boys than in girls. The rate of current using e-cigarette was 2.07% for rural and 0.48% for urban. Technical secondary school students had the highest rate of tried to use e-cigarette and susceptibility to future e-cigarette use (13.53%, 6.91%). Junior school students (2.96%) had the lowest level of susceptibility to future tobacco use. The rate of tried e-cigarette use and current e-cigarette use and susceptibility to future e-cigarette use were higher in the group of "One of students' parents was smoker" (8.63%, 2.19%, 5.23%). The highest rate of current smoking was found in the group of "Weekly allowance more than 50 Yuan" (10.02%, 2.54%, 6.29%). Compared to technical secondary school students, senior school student (OR=0.57) and junior school students (OR=0.45) were less likely to try to use e-cigarette. Students whose weekly allowance were less than 20 Yuan were less likely to try to use e-cigarette (OR=0.49). Students who were boys (OR=5.44) and one of their parents was smoker (OR=1.59) were more likely to try to use e-cigarette. Conclusions: There were middle school students with tried e-cigarette use and current e-cigarette use, especially in technical secondary schools. The prevalence of e-cigarette using among middle school students increased with age. It is important to further spread of e-cigarette knowledge widely and deeply, and reduce the susceptible population of adolescents using e-cigarettes.

Analysis of typical practical problems and countermeasures of supply chain management mode in public hospitals / 药学实践杂志

Objective to analyze the differences and changes before and after the introduction of supply processing distribution (SPD) supply chain management mode in a public hospital, analyze the typical problems existing in the clinical practice and development of SPD mode, and explore the countermeasures to improve the SPD supply chain management. Methods the changes of 20 management functions before and after the introduction of SPD supply chain management mode were compared. The advantages and disadvantages of SPD management mode were analyzed. The improvement measures and countermeasures were proposed. Results among the 20 management functions, 11 of them were reduced, 5 of them were equal, and 4 of them were increased. The overall efficiency of hospital management was improved. Because the external medicine supplier has not been included in the hospital rules, regulations system and process. The role positioning was not clear. There were defects in institutional and continuous guarantee. Conclusion SPD supply chain management mode can be improved and innovated to promote the supply channel reform of drugs and medical consumables, and improve the fine management level of drugs and medical consumables.

Comparison of neoadjuvant chemotherapy followed by surgery vs. surgery alone for locally advanced gastric cancer: a meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer, but the effects on safety and survival are still controversial. The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery (NACS) and surgery alone (SA) for locally advanced gastric cancer.@*METHODS@#Databases (PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar) were explored for relative studies from January 2000 to January 2021. The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale, respectively. The Review Manager software (version 5.3) was used to perform this meta-analysis. The overall survival was evaluated as the primary outcome, while perioperative indicators and post-operative complications were evaluated as the secondary outcomes.@*RESULTS@#Twenty studies, including 1420 NACS cases and 1942 SA cases, were enrolled. The results showed that there were no significant differences in overall survival (P = 0.240), harvested lymph nodes (P = 0.200), total complications (P = 0.080), and 30-day post-operative mortality (P = 0.490) between the NACS and SA groups. However, the NACS group was associated with a longer operation time (P < 0.0001), a higher R0 resection rate (P = 0.003), less reoperation (P = 0.030), and less anastomotic leakage (P = 0.007) compared with SA group.@*CONCLUSIONS@#Compared with SA, NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage. While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.

To study the correlation between LI-RADS category with tumor differentiation, Ki67 index, microvascular infiltration, and prognosis in HCC / 中华肝胆外科杂志

Objective:To study the correlation between liver imaging reporting and data system (LI-RADS) category with tumor differentiation, Ki67 index, microvascular infiltration, and predictive prognosis in hepatocellular carcinoma (HCC).Methods:We retrospectively analyzed the clinical and radiological data of 178 patients with HCC who were confirmed by histopathological studies after liver resection between January 2015 and September 2020 at Lishui Central Hospital and Lishui People’s Hospital. There were 156 males and 22 females, with age of (57±10) years old. These patients were assessed for LI-RADS categories according to the 2018 version of LI-RADS, and they were divided into 4 groups according to the assessment results: 12 patients with LI-RADS-3 (the LI-RADS-3 group); 26 patients with LI-RADS-4 (the LI-RADS-4 group); 102 patients with LI-RADS-5 (the LI-RADS-5 group); and 38 patients with LI-RADS-M (the LI-RADS-M group). The patients' general information, tumor markers, pathology and other clinical data were recorded. Correlation analysis between the LI-RADS category with pathology was performed by the Kendall's tau-b test. Survival analysis between groups was performed by the Kaplan-Meier analysis. The Cox regression risk model was used to analyze the relationship between these variables with the risk of death.Results:The Kendall's tau-b test showed that LI-RADS category was positively correlated with the degree of tumor differentiation ( t=0.204, P=0.002), but not with microvascular infiltration and Ki 67 index ( P>0.05). All patients were followed up for 4.2 to 84.2 months (median follow-up 36.3 months). By the end of follow-up, 31 patients had died and 147 patients were alive. The cumulative 1-year and 3-year survival rates of the LI-RADS-5 group were 97% and 90% respectively, which were significantly higher than those in the LI-RADS-M group (81% and 63%), and the LI-RADS-4 group (96% and 81%), ( P<0.05). The cumulative 1-year and 3-year survival rates of patients in the LI-RADS-3 group were 100% and 67% respectively, and there was no statistically significant difference with the LI-RADS-5 group ( P>0.05). The Cox multivariate regression analysis showed that tumor glycoantigen 199 (>50 μl/ml) to be an independent influencing factor in survival of HCC patients ( HR=0.43, 95% CI: 0.24-0.76, P=0.004). Conclusion:The LI-RADS category of HCC was positively correlated with the degree of tumor differentiation, and patients with HCC meeting the LI-RADS-5 criteria had relatively better prognosis.

Establishment and validation of a new predictive equation with multiple risk factors for the development of cardiorenal syndrome type 1 in patients with acute myocardial infarction / 中华心血管病杂志

Objective: To investigate the independent risk factors of cardiorenal syndrome type 1 (CRS1) in patients with acute myocardial infarction (AMI) and to build a predictive equation for the development of CRS1 in these patients. Method: Consecutive inpatients with AMI, who hospitalized from January 2017 to December 2018 in the Hunan Provincial People's Hospital, were enrolled in this case-control study. Patients were divided into CRS1 group and non-CRS1 group according to the presence or absence of CRS1.The clinical data were collected through the electronic medical record system of Hunan Provincial People's Hospital. The matching process was conducted with a minimum-distance scoring method and a 1∶1 match between the CRS1 group and the no-CRS1 group, the propensity score was calculated through the logistic regression model. Factors with statistically significant differences in univariate analysis were included in the multivariate logistic regression model to analyze the risk factors of AMI patients with CRS1, then the independent risk factors were used to establish a predicting equation for CRS1 by logistic regression function for model building. Area under the curve (AUC) value and the best cut-off value of the combined predictors was determined according to the ROC curve. Python 3.8 software was used to perform 10-fold cross-validation on modeling samples. Results: A total of 942 patients were included, there were 113 cases in CRS1 group and 829 cases in non-CRS1 group. Ultimately, 99 CRS1 patients were successfully matched to 99 non-CRS1 patient using 1∶1 matching. After propensity score matching, the baseline age and sex along with heart rate, mean arterial pressure, percentage of people with a history of diabetes, hypertension, ST-segment elevation myocardial infarction, myocardial ischemia time, angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers use, and β receptor blocker use were similar between the two groups(all P>0.05). The contrast agent dosage was also similar between the two groups (P=0.266). The peak cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), white blood cell count, base estimated glomerular filtration rate (eGFR), albumin and hemoglobin levels were statistically significant between the two groups (all P<0.05). Multivariate logistic regression analysis showed that decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count were independent risk factors of CRS1 in AMI patients (all P<0.01).The predicting equation of the combined predictor was established by transforming the logistic model equation, L=0.031×cTnI+0.000 2×NT-proBNP-0.024×eGFR+0.254×white blood cell count, where L represented the combined predictor. ROC curve analysis indicated that the AUC of the peak cTnI, NT-proBNP, baseline eGFR, white blood cell count, and combined predictor were 0.76, 0.85, 0.79, 0.81, and 0.92 respectively (all P<0.05), and the cutoff value of combined predictor was 2.6. The AUC of ROC curve after the model's ten-fold cross validation was 0.89. Conclusions: Decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count are the independent risk factors for CRS1 in AMI patients. The combined predictor equation based on the above 4 biomarkers presents a good predictive value for CRS1 in AMI patients.

Research progress on adverse effects of fine particulate matter constituent exposure on ischemic heart disease / 公共卫生与预防医学

Ambient fine particulate matter (PM2.5) is a mixture consisting of a wide range of chemical constituents including carbonaceous aerosols, water soluble ions and inorganic elements, and has become the major air pollutant in most cities in China. Evidence suggests that exposure to ambient PM2.5 induces damage on the cardiovascular system and can increase risk of the development and mortality of ischemic heart diseases (IHD). However, the effects of exposure to specific PM2.5 constituents on IHD remain unclear, and its underlying mechanisms are yet to be investigated. Here we reviewed studies investigating the association of short- and long-term exposure to specific PM2.5 constituents with IHD, which may provide useful clues for future relevant studies.

Correlation between serum microRNA-497 expression and invasion, metastasis and prognosis of colorectal cancer / 中国医师杂志

Objective:To investigate the correlation between microRNA-497 (miR-497) expression and invasion and metastasis and prognosis of colorectal cancer (CRC).Methods:The expression of miR-497 in 93 CRC patients (CRC group), 30 colorectal adenoma polyps (colorectal adenomatous polyp group) and 30 healthy patients (normal control group)were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR); meanwhile, the content of serum carcinoembryonic antigen (CEA) was detected by chemiluminescence; After 3 years follow-up, the expression of miR-497 was measured again; the correlation between the expression of miR-497 and the clinicopathological characteristics and prognosis of CRC was analyzed.Results:The expression of miR-497 in CRC group was significantly lower than that at the end of postoperative treatment, adenomatous polyps group and normal control group ( P<0.01), and the content of CEA in CRC group was significantly higher than that at the end of postoperative treatment, adenomatous polyps group and normal control group ( P<0.01); At the end of postoperative treatment, the expression of serum miR-497 in CRC group was lower than that in normal control group ( P<0.05), and the content of serum CEA was higher than that in normal control group ( P<0.05). The diagnosis positive rate of serum miR497 expression in CRC group was significantly higher than that of serum CEA ( P<0.01), and they showed no correlation ( r=0.232, P>0.05). The pre-and post-operative serum miR-497 expression levels in the recurred and metastasis group were significantly lower than those in the no postoperative recurrence and metastasis group ( P<0.01). The preoperative expression of miR-497 was related to the differentiation degree of CRC, tumor node metastasis (TNM) stage, lymph node metastasis, distant metastasis and survival period ( P<0.01), but not with the age, sex, tumor size and location of the patients ( P>0.05). Cox multivariate analysis showed that tumor differentiation, TNM stage, preoperative miR-497 expression, lymph node metastasis and distant metastasis were all independent risk factors influencing prognosis of CRC patients ( P<0.05); The survival rate of 1, 2, 3 years in the miR-497 low expression group was lower than that in the miR-497 high expression group ( P<0.05). Conclusions:The preoperative low serum miR-497 expression levels are closely relative with invasion and metastasis and poor prognosis of CRC, and can be a prognostic indicator of CRC. The reduced postoperative serum miR-497 expression levels may be a predictor of the postoperative recurrence and metastasis of CRC.

Differential expression analysis and regulatory network construction of miRNA and genes in osteoporosis / 医学研究生学报

ObjectiveMicroRNAs (miRNA) play an important role in the development and regression of osteoporosis. This study aims to screen for miRNAs and genes closely related to osteoporosis, and to complete the construction of a miRNA-mRNA regulatory network of osteoporosis.MethodsThe gene chip expression profile of osteoporosis was obtained through the GEO database, and the differentially expressed genes (DEGs) and miRNAs were analyzed and screened via GEO2R. We used volcanic maps to display differential genes and miRNAs, and completed the GO and KEGG pathway analysis through the David online database. The String online database is used to complete PPI protein network analysis. The TargetScan, miRTarBase and miRDB were used to predict the targeted genes. Finally, the PPI and miRNA-mRNA regulatory networks were visualized by Cytoscape software.ResultsWe obtained 15 differential miRNAs and 174 differentially expressed genes through screening. The GO enrichment analysis mainly focused on drug response, angiogenesis, ion transport, regulation of small GTPase mediated signal ransduction, adaptive immune response, etc. NF-κB signaling pathway and HIF-1 signal were obtained through KEGG enrichment analysis. We obtained 10 hub genes through the cytohubba plug-in. We also obtained 3065 targeted genes by processing of seven miRNAs, and then intersected them with 174 DEGs to obtain 44 intersection genes. Finally, we successfully constructed a regulation map of miRNA-mRNA network. The miR-194-5p is significantly up-regulated in osteoporosis.ConclusionThe miR-194-5p might play an important role in osteoporosis by regulating its target gene CDH2, which provides candidate targets for the diagnosis and treatment of osteoporosis.

Considerations on the prevention and control of the novel coronavirus pneumonia / 医学研究生学报

As a new infectious disease, the novel coronavirus pneumonia (NCP) has continued to spread since the end of 2019. It has now been classifiedas a Class B infectious disease, and the preventive and control measures of Class A infectious diseases have been adopted. With reference to the official documents issued by WHO and National Health Commission, PRC and the latest research, this paper discusses the prevention and control of the NCP from its epidemiology, evolutionary sources, prevention and control, and so forth.

Thermosensitive gel of polysaccharide from Ganoderma applanatum combined with paclitaxel for mice with 4T1 breast cancer / 中国中药杂志

Polysaccharide from Ganoderma applanatum has the activities of anti-tumor and enhancing immune function. There were no reports on antitumor effect of its intratumoral injection. In this study, the polysaccharide was extracted from G. applanatum by water extraction and alcohol precipitation, and purified by ceramic membrane after removing protein by Sevage method. The total polysaccharide content from G. applanatum(PGA)was about 63%. The combination of PGA and paclitaxel showed synergistic effect on cytotoxicity of 4 T1 cells at lower concentrations in vitro. In addition, the growth curve of 4 T1 cells showed that PGA could retard the growth of 4 T1 cells gradually. The PGA thermosensitive gel(PGA-TG)was prepared by using poloxamer 188 and 407. The gel temperature was 36 ℃, and the PGA-TG could effectively slow down the release rate of PGA in vitro. 4 T1 breast cancer-bearing mice were used as a model to evaluate the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound paclitaxel(nab-PTX). In high and low dose PGA groups, each mice was given with 2.25, 1.125 mg PGA respectively, twice in total, and the dosage of paclitaxel was 15 mg·kg~(-1), once every 3 days, for a total of five times. The tumor inhibition rate was 29.65% in the high dose PGA-TG group, 58.58% in the nab-PTX group, 63.37% in low dose PGA-TG combined with nab-PTX group, and 68.10% in high dose PGA-TG combined with nab-PTX group respectively. The inhibitory effect in high dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in nab-PTX group(P<0.05). The results showed that paclitaxel therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4 T1 mice and reduce the side effects of chemotherapy.

Revealing the synergistic mechanism of Shenfu Decoction for anti-heart failure through network pharmacology strategy / 中国天然药物

The present study was designed to investigate the targets and synergistic mechanism of Shenfu Decoction (SFD) in the treatment of heart failure. A heart failure animal models was established to evaluate the pharmacological effects of SFD for anti-heart failure, then constructed ingredient-target interaction network by developing ingredient and target databases, the Discovery sdudio software was used for molecular docking. In addition, we validated the predicted protein targets of active ingredients in SFD by using surface plasmon resonance (SPR) technology. Our results demonstrated that SFD could enhance ejection fraction, alleviate myocardial histopathological characteristics, and reduce the level of angiotensin converting enzyme (ACE), aldosterone (ALD), atrial natriuretic polypeptide (ANP) and Renin (REN) in heart failure rat model. In addition, the ingredient database including 349 constituents and target database including 236 proteins were established, and 75 proteins were screened and identified by molecular docking strategy. 22 core target proteins were identified through network pharmacology, and the component-core target network was constructed. Finally, the affinity between the compounds and targets were verified by the SPR analysis method. The present study suggested that SFD may act on ACE 2, REN, ACE, ICAM-1, EGF, HTR2B, PARP1, NPPB and other proteins through AC, BAC, ACN, Re, Rg1, Rb1 to exert synergistic effects against heart failure.