Therapeutic effect of Xiayuxue decoction on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of action of Xiayuxue decoction in inhibiting nonalcoholic fatty liver disease （NAFLD） induced by high-fat diet in mice by regulating nucleotide binding oligomerization domain like receptor containing pyrin domain protein 6 （NLRP6）. MethodsA total of 15 male C57BL/6 mice were randomly divided into low-fat diet （LFD） group， high-fat diet （HFD） group， and Xiayuxue decoction-HFD group （XYXD group）， with 5 mice in each group. Liver function parameters （alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］） and blood lipid metabolic indicators （triglycerides ［TG］ and total cholesterol ［TC］） were measured； HE staining and oil red O staining were performed for liver tissue to observe histomorpholoty and lipid droplet deposition； quantitative real-time PCR was used to measure the expression levels of inflammatory factors （tumor necrosis factor-α ［TNF-α］， interleukin-1β ［IL-1β］， interleukin-18 ［IL-18］， and NLRP6） in liver tissue； Western blot was used to measure the protein expression levels of NLRP6， nuclear factor-kappa B （NF-κB）， and NF-κB p65； immunohistochemistry was used to measure the expression of NLRP6 and CD68. Mouse Raw264.7 cells were treated with palmitic acid （PA）， lipopolysaccharide， and serum containing Xiayuxue decoction to observe inflammation. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the LFD group， the HFD group had significant increases in the serum levels of ALT， AST， TC， and TG （all P<0.05）. Liver histopathological examination showed that the HFD group had marked hepatic steatosis and a signficant increase in NAS score （P<0.05）， and quantitative real-time PCR showed significant increases in the inflammatory factors such as IL1β and IL-18 and a significant reduction in the expression of NLRP6 （all P<0.05）. Immunohistochemistry showed that the expression of NLRP6 showed a similar trend as that of the macrophage marker CD68. Western blot showed that after the downregulation of NLRP6 expression， there was a significant increase in phosphorylated NF-κB p65 （P<0.05）. Compared with the HFD group， Xiayuxue decoction effectively improved liver inflammation， upregulated the expression of NLRP6， and downregulated phosphorylated NF-κB p65 in HFD mice （all P<0.05）. After Raw264.7 cells were treated with PA， NLRP6 was downregulated to promote the progression of inflammation （P<0.05）， and treatment with Xiayuxue decoction could upregulate NLRP6 and inhibit inflammation NF-κB （P<0.05）. ConclusionXiayuxue decoction can effectively improve hepatic steatosis and liver inflammation in a mouse model of NAFLD， possibly by regulating NLRP6/NF-κB to alleviate macrophage activation.

Role of podoplanin in hepatic stellate cell activation and liver fibrosis / 临床肝胆病杂志

ObjectiveTo investigate the role and mechanism of podoplanin （PDPN） in hepatic stellate cell （HSC） activation and liver fibrosis. MethodsLiver biopsy samples were collected from 75 patients with chronic hepatitis B who attended Department of Infectious Diseases， Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine， for the first time from September 2019 to June 2022， and RT-PCR and immunohistochemistry were used to measure the expression of PDPN in liver tissue of patients in different stages of liver fibrosis. A total of 12 male C57/BL6 mice were randomly divided into control group and model group. The mice in the model group were given intraperitoneal injection of 10% CCl4， and those in the control group were injected with an equal volume of olive oil， for 6 weeks. HE staining and Sirius Red staining were used to observe liver histopathological changes； primary mouse liver cells were separated to measure the mRNA expression of PDPN in various types of cells； primary mouse HSCs were treated with PDPN protein， followed by treatment with the NF-‍κB inhibitor BAY11-708， to measure the expression of inflammatory factors in HSCs induced by PDPN. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Spearman correlation analysis was used to investigate data correlation. ResultsAs for the liver biopsy samples， there was a relatively low mRNA expression level of PDPN in normal liver， and there was a significant increase in the mRNA expression level of PDPN in liver tissue of stage S3 or S4 fibrosis （all P<0.001）. Immunohistochemical staining showed that PDPN was mainly expressed in the fibrous septum and the hepatic sinusoid， and the PDPN-positive area in S4 liver tissue was significantly higher than that in S0 liver tissue （t=8.892， P=0.001）. In normal mice， PDPN was mainly expressed in the hepatic sinusoid， and there was a significant increase in the expression of PDPN in CCl4 model mice （t=0.95， P<0.001）， mainly in the fibrous septum. RT-PCR showed a significant increase in the mRNA expression of PDPN in the CCl4 model mice （t=11.25， P=0.002）. Compared with hepatocytes， HSCs， Kupffer cells， and bile duct endothelial cells， hepatic sinusoidal endothelial cells showed a significantly high expression level of PDPN （F=20.56， P<0.001）. Compared with the control group， the primary mouse HSCs treated by PDPN protein for 15 minutes showed significant increases in the mRNA expression levels of the inflammation-related factors TNFα， CCL3， CXCL1， and CXCR1 （all P<0.05）， and there were significant reductions in the levels of these indicators after treatment with BAY11-7082 （all P<0.05）. ConclusionThere is an increase in the expression of PDPN mainly in hepatic sinusoidal endothelial cells during liver fibrosis， and PDPN regulates HSC activation and promotes the progression of liver fibrosis via the NF-κB signaling pathway.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project / 老年心脏病学杂志（英文版）

BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Exploring of Transformation Rule of Saponins in Polygalae Radix Before and After Processing Based on Simulated Processing Technology / 中国实验方剂学杂志

ObjectiveTo investigate the transformation mechanism and content variation of saponins from Polygalae Radix before and after being boiled with licorice juice and water. MethodSimulated licorice juice boiled products and simulated water boiled products of onjisaponin B， onjisaponin Z， onjisaponin F， polygalasaponin ⅩⅩⅧ were prepared by simulated processing technology， and analyzed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap/MS）. Then the contents of onjisaponin B， onjisaponin Z， onjisaponin F， polygalasaponin ⅩⅩⅧ and tenuifolin in Polygalae Radix， licorice-boiled Polygalae Radix and water-boiled Polygalae Radix were determined by UPLC-triple quadrupole tandem mass spectrometry（UPLC-QQQ-MS/MS）. ResultDuring the boiling process with licorice juice and water， onjisaponin B could be hydrolyzed to produce 4-methoxycinnamic acid， desacylsenegin Ⅲ， polygalasaponin ⅩⅩⅧ and tenuifolin， onjisaponin Z could be hydrolyzed to produce 3，4，5-trimethoxycinnamic acid， onjisaponin TF， polygalasaponin ⅩⅩⅧ and tenuifolin， onjisaponin F could be hydrolyzed to produce 3，4，5-trimethoxycinnamic acid， onjisaponin G， polygalasaponin ⅩⅩⅧ and tenuifolin， and polygalasaponin ⅩⅩⅧ was hydrolyzed to produce tenuifolin. After being boiled with licorice juice or water， the content of onjisaponin B decreased significantly（P<0.05， P<0.01）， but the contents of onjisaponin Z， onjisaponin F， polygalasaponin ⅩⅩⅧ and tenuifolin increased significantly（P<0.05， P<0.01） in Polygalae Radix. Compared with the water-boiled products， the contents of onjisaponin Z and tenuifolin increased significantly（P<0.05， P<0.01）， and the change of tenuifolin content was the most significant in the licorice-boiled products.However， there was no significant difference in the content of onjisaponin B， onjisaponin F and polygalasaponin ⅩⅩⅧ between the water-boiled products and the licorice-boiled products. ConclusionBeing boiled with licorice juice or water can hydrolyze onjisaponin B， onjisaponin Z， onjisaponin F and polygalasaponin ⅩⅩⅧ， and generate secondary glycosides and aglycones（organic acids） through deglycosylation， which leads to obvious changes in the contents of onjisaponins after Polygalae Radix being processed.It is inferred that licorice juice can promote the hydrolysis of some onjisaponins in Polygalae Radix to onjisaponin Z and tenuifolin.This study provides an experimental basis for revealing processing mechanism of Polygalae Radix.

Analysis of satisfaction and influencing factors of scientific research incentive mechanisms for young medical staff in a children′s hospital in Beijing / 中华医学科研管理杂志

Objective:This study aims to explore the satisfaction and influencing factors of scientific research incentive mechanisms for young medical staff in a children′s hospital in Beijing, and to provide references for the management department to develop relevant incentive strategies.Methods:A satisfaction questionnaire survey of scientific research incentive mechanisms was carried out during April and May, 2022. Collected data were analyzed by rank sum test and ordered logistic regression.Results:The level of overall satisfaction of 339 young medical staffs was 81.42%. The satisfaction rate of incentive factors was 80.50% and hygiene factors was 77.51%.According to the findings, there were significant differences in educational backgrounds, professional titles and job types, hygiene factors, and incentive factors ( P<0.05). The contributing factors of the job satisfaction were professional title, hygiene factors and incentive factors. Conclusions:The overall satisfaction with the incentive work of the young research staff surveyed was relatively at high-level. It is necessary to improve tailed hygiene factors to meet the characteristics young medical staff, such as setting up full-time scientific research working hours, exploring the establishment of diversified of scientific research sharing mechanisms to increase the utilization of the scientific research platform. It is important to enhance incentive factors to establish a long-term incentive mechanism for young personnel, such as setting up interdisciplinary research projects, exploring the establishment of a recommendation mechanism for outstanding young talents, in order to provide them with more opportunities for further intensive training.

Optimization practice of youth research project management in children′s hospital: Based on the situation and demand of National Natural Science Youth Foundation in Beijing Children′s Hospital / 中华医学科研管理杂志

Objective:The study takes the Youth Research Project of National Natural Science Foundation of China (NSFC) as an example, analyzes the development and management optimization strategy of such research project in a children′s hospital, to provide reference for the training of pediatric young talents.Methods:Personnel interview and questionnaire survey were adopted to analyze the common characteristics of project application and approval, trend of change, demand and bottleneck challenges of the NSFC Youth Research Project from 2016 to 2022.Results:The total number of approved project were increasing while the rate of the bids fluctuated, and the distribution of department, gender and age are not balanced, full-time scientific research personnel, male, young age and other factors have the advantages of being approved. Five influential factors, including scientific research accomplishment, supporting conditions, research foundation, methods & skills, and scientific research atmosphere and environment, were identified as necessary components of getting funded. The survey also founded that two thirds of the needs run through the whole application process that from the topic selection, nurtured seed-funding, team-building and proposal development.Conclusions:This study puts forward a management plan for youth scientific research projects in children′s hospital from three aspects that including hospital, department and individual. The management department should strengthen the transformation from " full application" to " effective application" , at the same time, more attention should be paid to the selection, training and resource allocation to further optimize the training strategy of youth talents.

Influence of Helicobacter pylori infection on anxiety and depression in patients with chronic gastritis / 中华消化杂志

Objective:To evaluate the influence of Helicobacter pylori ( H. pylori) infection on anxiety and depression in patients with chronic gastritis. Methods:From December 1 2020 to June 30 2021, 387 patients with chronic gastritis who visited the outpatient Department of Gastroenterology, the First Hospital Affiliated to Air Force Medical University were continuously recruited. According to the status of current H. pylori infection, the patients were divided into H. pylori uninfected group and H. pylori infected group. The general demographic information of patients was collected. Hamilton anxiety scale, Hamilton depression rating scale-24, Pittsburgh sleep quality index (PSQI) and gastrointestinal symptom rating scale (GSRS) were filled in. The detection rates of anxiety and depression were compared between the H. pylori uninfected group and the H. pylori infected group according to demographic characteristics. Chi-square test and multiple logistic regression analysis were used for statistical analysis. Results:Finally, 360 patients with chronic gastritis were enrolled, including 200 patients in H. pylori uninfected group and 160 patients in H. pylori infected group. The detection rates of anxiety and depression of the H. pylori infected group were both higher than those of the H. pylori uninfected group (48.1%, 77/160 vs. 30.0%, 60/200; 25.0%, 40/160 vs. 12.5%, 25/200), and the differences were statistically significant ( χ2=12.39 and 9.39, P<0.001 and=0.002). The detection rate of anxiety of male patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (45.1%, 32/71 vs. 24.5%, 27/110); the detection rate of depression of female patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (30.3%, 27/89 vs. 11.1%, 10/90), and the differences were statistically significant ( χ2=8.27 and 10.09, P=0.004 and 0.001). The detection rates of anxiety and depression of patients less than 48 years old in the H. pylori infected group were both higher than those in the H. pylori uninfected group (46.2%, 37/80 vs. 21.9%, 21/96; 20.0%, 16/80 vs. 7.3%, 7/96), and the differences were statistically significant ( χ2=11.73 and 6.20, P=0.001 and 0.013). The detection rates of anxiety and depression of the patients with high school education and below in the H. pylori infected group were higher than those in the H. pylori uninfected group (56.5%, 48/85 vs. 31.7%, 38/120; 32.9%, 28/85 vs. 14.2%, 17/120), and the differences were statistically significant ( χ2=12.57 and 10.24, P<0.001 and =0.001). The results of multivariate analysis showed that H. pylori infection, history of hypertension, PSQI score ≥8, GSRS score ≥7, chronic superficial gastritis and chronic atrophic gastritis were independent risk factors of anxiety in patients with chronic gastritis( P<0.001, =0.013, =0.001, <0.001, =0.036, =0.021), and the risk of anxiety of patients with H. pylori infection was 2.509 times as much as that in uninfected patients (95% confidence interval 1.512 to 4.163). H. pylori infection, PSQI score ≥8, GSRS score≥7, and having overnight dish ≥3 times per week all were independent risk factors of depression in patients with chronic gastritis( P=0.004, =0.002, <0.001, =0.001). The risk of depression in patients with H. pylori infection was 2.563 times as much as that in uninfected patients (95% confidence interval 1.356 to 4.846). Conclusion:H. pylori infection is correlated to anxiety and depression in patients with chronic gastritis, and it is an independent risk factor of anxiety and depression in patients with chronic gastritis.

A single-center research of peroral endoscopic myotomy for primary achalasia in patients over 60 years old / 中华消化内镜杂志

Objective:To explore the therapeutic effect of peroral endoscopic myotomy (POEM) for primary achalasia (AC) in patients aged over 60 years.Methods:Data of 146 patients aged ≥60 years (the elderly group) and 146 patients aged 18-59 years (the adult group) who received POEM from November 2010 to September 2019 at the Digestive Endoscopy Center of PLA General Hospital were retrospectively analyzed. Baseline data, surgery data, surgery-related complications and surgery-related efficacy were compared.Results:There was no significant difference in gender, Ling classification, HRM classification or previous treatment between the two groups ( P>0.05). All 292 patients successfully underwent POEM surgery. The clinical success (Eckardt score ≤3) rates in the elderly group and the adult group were 96.33% (105/109) and 96.77% (90/93), respectively with no significant difference between the two groups ( χ2=0.030， P>0.05). There was no significant difference in the length of myotomy between the two groups (7.09±2.49 cm VS 7.12±2.24 cm， t=0.472， P>0.05). Complications occurred in 26 cases (17.81%) in the elderly group and 21 cases (14.38%) in the adult group with no significant difference between the two groups ( χ2=0.634， P>0.05). There was no significant difference in the postoperative hospital stay (12.61±9.69 days VS 11.00±4.43 days, t=1.825, P>0.05) or the incidence of gastroesophageal reflux [43.33% (13/30) VS 51.52% (17/33), χ2=0.422, P>0.05] between the elderly group and the adult group. Conclusion:The efficacy of POEM for AC patients over 60 years old is equivalent to that of adult patients, and the incidence of complications is similar. POEM is safe and effective for AC patients over 60 years old.

Combining neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicted the prognosis of hepatocellular carcinoma patients after liver transplantation / 中华器官移植杂志

Objective:To explore the prognostic values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio(PLR)and NLR-PLR score for carcinoma(HCC)patients undergoing liver transplantation(LT).Methods:From July 2015 to October 2021, clinical data are retrospectively reviewed for 110 HCC patients undergoing orthotopic LT at Third Hospital of Hebei Medical University.The values of NLR and PLR were calculated.And the cut-off values of NLR and PLR were obtained by receiver operating characteristic (ROC) curve and then grouped according to the cut-off values.Survival time is analyzed by Kaplan-Meier method and Log-rank test performed for inter-group comparison.Univariate and multivariate analyses are performed based on Cox proportional risk regression model.NLR <3.37 and PLR <105.96 are denoted as 0 point while NLR ≥3.37 and PLR ≥105.96 as 1 point.Two points are added up as NLR-PLR score.According to NLR-PLR score, they are divided into 3 groups of 0, 1 and 2.Results:Median overall survival(OS)is 27 months in patients with NLR-PLR score 0, 26.5 months in patients with NLR-PLR score 1 and 6 months in patients with NLR-PLR score 2.Median OS in patients with NLR-PLR score 2 is significantly shorter than that in those with NLR-PLR score 0/1.And the difference is statistically significant( P<0.001).Median disease-free survival(DFS)is 24.5 months in NLR-PLR 0 group, 24 months in NLR-PLR 1 group and 6 months in NLR-PLR 2 group.The difference is statistically significant( P=0.002).Univariate analysis show that Child-Pugh grade, MELD score, NLR/PLR level, NLR-PLR score, complying with University of California San Francisco Criteria(UCSF)criteria and absence/presence of microvascular invasion(MVI)have an impact on patient survival.Further multivariate analysis show that NLR-PLR score, complying with UCSF criteria and MELD score are independent risk factors affecting patients' prognosis and survival. Conclusions:NLR, PLR and NLR-PLR score may predict long-term survival of patients.And NLR-PLR score is an independent risk factor for patient survival.It has more predictive value than NLR/PLR.

The value of superior mesenteric artery preferential approach in the treatment of borderline resectable pancreatic head cancer / 中华普通外科杂志

Objective:To evaluate superior mesenteric artery preferential approach in the borderline resectable pancreatic head cancer.Methods:The clinical and follow-up data of 90 patients with borderline resectable pancreatic head cancer who underwent radical pancreatoduodenectomy at Beijing Chaoyang Hospital,Capital Medical University from Jan 2015 to Dec 2021 were analyzed.Results:After exploring the superior mesenteric artery in the lower colon area to confirm the vascular invasion meet the resection criteria, the blood supply is cut off first, then the tumors were resected en bloc, with the invaded vessels resected and reconstructed or replaced. All 90 patients successfully completed the operation without perioperative death. Pathology established pancreatic ductal adenocarcinoma. The 1-year, 2-year, and 3-year disease-free survival rates of patients in the arterial priority approach group were 68.2%, 60.4%, and 54.3%, while the 1-year, 2-year, and 3-year disease-free survival rates of patients by conventional approach were 58.4%, 26.4%, and 11.7% ( P=0.001). Conclusion:The superior mesenteric artery preferential approach in the inferior colon region can prolong the survival time of patients after surgery, and reduce the recurrence.

Mid-term efficacy of surface knee prosthesis combined with bionic block in joint reconstruction after resection of giant cell tumor in proximal tibia / 中华骨科杂志

A total of 6 patients were treated with surface knee joint prosthesis combined with 3D-printed customized bionic tibial block for reconstruction of bone defect after giant cell tumor (GCT) in proximal tibia (1 male and 5 females, aged 50, 40, 68, 53, 35, 42, respectively). 3 patients with primary and 3 patients with recurrence of GCT. After resection of the tumor, the bone defect was filled with 3D-printed block combined with surface knee prosthesis, the surrounding ligaments were reconstructed with microporous structure and artificial mesh. All cases were followed up for 60, 90, 60, 60, 75, and 50 months, respectively. During the follow-up, there was no local recurrence, no radiolucent lines around prosthesis, and no signs of loosening. The clinical scores of the American Knee Society Score (KSS) were 87, 92, 85, 90, 95 and 78. The functional scores were 70, 100, 70, 100, 100 and 80 respectively. Musculoskeletal Tumor Society Score (MSTS) were 27, 28, 26, 26, 26, 27, respectively. Surface knee prosthesis combined with bionic block can effectively fill the bone defect after resection of GCT in proximal tibia, achieve anatomical and functional reconstruction of knee joint.

The effect of feeding methods on fecal metabolites of infants delivered by cesarean section based on non-targeted metabolomics / 中华实用儿科临床杂志

Objective:To explore the effect of breast feeding versus mixed feeding on fecal metabolites of infants delivered by cesarean section.Methods:This was a cross-sectional study.Fecal samples were collected from 23 healthy 1-month-old infants delivered by cesarean section from autumn 2021 and winter 2022 in two maternal and infant care facilities in the North and South of Xi′an city.The samples were divided into the breast feeding group (11 cases) and mixed feeding group (12 cases). Fecal metabolites were analyzed by the non-targeted metabolomic approach and gas chromatography-mass spectrometry coupling, and differentially expressed fecal metabolites between groups were screened using the non-parametric Mann- Whitney U test.Metabolic pathways enriched in them were further analyzed. Results:A total of 155 metabolites were characterized, including 57 sugars and sugar derivatives, 34 fatty acids, 25 organic acids, 22 amino acids, 8 esters, 4 nucleosides, 3 vitamins and 2 other substances.The relative contents of the differentially expressed fecal metabolites were measured, and it was found that some types of sugars and sugar derivatives were highly expressed in the fecal samples of breast feeding group, while amino acids, organic acids and fatty acids were highly expressed in those of the mixed feeding group.A total of 28 metabolic pathways enriched in differentially expressed fecal metabolites were obtained.Among them, alanine, aspartic acid and glutamic acid metabolism, valine, leucine and isoleucine metabolism, arginine metabolism and the tricarboxylic acid (TCA) cycle influenced infant health.Conclusions:Feeding methods have an effect on the fecal metabolites in infants delivered by cesarean section born infants, and mixed feeding may speed up the process of TCA cycle and amino acid metabolism in the intestine of infants delivered by cesarean section to a certain extent.

Clinical study of intra-articular injection of autologous PRP combined with Tongbi San fumigation in the treatment of early knee osteoarthritis / 国际中医中药杂志

Objective:To evaluate the efficacy of intra-articular injection of autologous platelet-rich plasma (PRP) combined with Tongbi Powder fumigation in the treatment of early knee osteoarthritis (KOA).Methods:Randomized controlled trial. Totally 160 patients with KOA in Tai'an Second Hospital of Traditional Chinese Medicine were enrolled between March 2021 and March 2022. According to random number table method, they were divided into two groups, with 80 cases in each group. The control group was given routine treatment, while observation group was given intra-articular injection of autologous PRP combined with Tongbi Powder fumigation. All were treated for 3 weeks. The knee function was evaluated by Western Ontario and McMaster University (WOMAC) osteoarthritis index. The activities of daily living were evaluated by Lysholm knee scale (LKS). The pain degree was evaluated by VAS. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The adverse reactions during treatment were observed and recorded. The clinical efficacy was evaluated.Results:The total effective rate of the observation group was 95.0% (76/80), and that of the control group was 77.5% (62/80), with statistical significance ( χ2=10.33, P<0.01). At 1, 3 and 6 months after treatment, the WOMAC score of the observation group was lower than that of the control group ( F=15.63, P<0.01), the LKS score was higher than that of the control group ( F=55.23, P<0.01), and the VAS score was lower than that of the control group ( F=11.93, P<0.01). After treatment, the observation group IL-1β [(51.75±2.74)μg/L vs. (63.38±3.31) μg/L, t=24.21], TNF- α [(10.58±1.25) μg/L vs. (11.62±1.84) μg/L, t=4.18] were lower than those in the control group ( P<0.01). The incidence of adverse reactions was 10.0% (8/80) in the observation group and 7.5% (6/80) in the control group, without statistical significance ( χ2=0.31, P=0.576). Conclusion:Intra-articular injection of autologous PRP combined with Tongbi San fumigation can effectively improve knee function and activities of living ability, relieve pain symptoms, reduce inflammatory response and improve clinical curative effect in early KOA.

Quality regulatory issues and suggestions for the Lonicerae Japonicae Flos with property of drug and food homologous substance / 国际中医中药杂志

In the context of the national strategy of promoting the research and development of food and drug homologous substances, it is necessary to study the regulatory model of food and drug homologous substances as food. Medicinal and food homologous substances are regulated as "Chinese medicinal materials" or "Chinese decoction pieces" in the drug category, and as "food and drug homologous substances", "agricultural products" or "traditional Chinese medicine healthy food" in the food category. Drug supervision focuses on quality, while food supervision focuses on safety, and it is worth exploring whether there is a blind spot in the supervision of food and drug substances completely based on the food concept. In this paper, Lonicerae Japonicae Flos, as drug and food homologous substance, is selected as the research object, and its quality regulation status is investigated by reviewing the relevant laws and regulations and standards on food, analyzing the quality information and test results of the samples, and analyzing the necessity of quality regulation when serving as food, in order to provide a basis and reference for the way food substances are regulated.

Effect of Wumeisan on Gut Lactase Activity and Microflora Diversity of Mice with Dysbacteriosis Diarrhea / 中国实验方剂学杂志

ObjectiveTo explore the effects of Wumeisan on gut lactase activity and microflora diversity of mice with dysbacteriosis diarrhea. MethodThe mice were randomly divided into 4 groups， namely， the normal group， the model group， and the low-dose and high-dose Wumeisan groups， with 8 mice in each group. The mouse model was made by gavage of mixed antibiotics for 7 d， and the low-dose and high-dose Wumeisan groups （5.98， 11.96 g·kg-1） were given gavage for 7 d continuously. The normal group and the model group were given the same volume of sterile water. The changes in the body weight， food intake， and diarrhea of mice were recorded. Feces were collected after the last administration， and the lactase activity was detected by the colorimetric method. The gut microbiota changes were detected by the 16S rRNA high-throughput sequencing technology. ResultCompared with those in the normal group， the mice in the model group had dilute and soft stools， reduced body mass， reduced food intake， reduced lactase activity， significantly reduced intestinal flora diversity， and significant changes in the relative abundance phylum and genus levels of flora. Compared with the model group， Wumeisan reduced the diarrhea rate of mice， promoted the rapid recovery of body weight and food intake， increased the lactase activity decreased by antibiotic， improved the community abundance and diversity of mice with dysbacteriosis， and made the species composition closer to that in the normal group. The abundance of three phyla （Bacteroidota， Proteobacteria， Verrucomicrobiota） and nine genera （Odoribacter， Enterococcus， Clostridium innocuum group， etc.） of mice with diarrhea were regulated by Wumeisan. Among them， norank f Muribaculaceae， norank f norank o Clostridia UCG-014， Lachnospiraceae NK4A136 group， and Odoribacter showed significant positive correlation with the body weight and lactase activity， and Escherichia-Shigella， Enterobacter， Enterococcus， and Clostridium innocuum group showed significant positive correlation with the diarrhea rate. Function prediction showed that the high-dose Wumeisan significantly reseted 6 functional levels of metabolism， genetic information processing， and human diseases， and had positive effects on endocrine and metabolic diseases， immune diseases， infectious disease， and parasitic infectious diseases. ConclusionWumeisan can relieve the symptoms of dysbacteriological diarrhea by increasing the lactase activity and regulating the gut microbiota composition.

Study on efficacy and regulation of inflammatory factors with oseltamivir phosphate by different time series of interventions in a murine model of influenza A H1N1 virus infection / 中国药理学通报

Aim To compare the effects of different time sequence interventions on virus infected mice by using oseltamivir (Tamiflu) as a "tool drug" in view of the current situation of the too early the administration time of antiviral in vivo experiment, so as to provide a basis for selecting a reasonable model intervention time point for antiviral drug research. Methods Balb/c mice were randomly divided into six groups. The virus infection model was established by intranasal infection with influenza virus (0.25 TCID50). Tamiflu-1 group and Tamiflu-2 group were administered orally on 1st and 4th day after exposure. The body mass, survival rate, organ index, viral load and inflammatory factor content were measured. Results Compared with the blank control group, the body weight of the mice in the model group decreased and the lung index increased significantly (P < 0.05). The expression levels of 13 inflammatory factors in model 2 group were significantly different ( P < 0.05). Compared with the model-1 group ,the lung index and spleen index of the Tamiflu-1 group decreased significantly (P < 0.05). Compared with the mode-2 group,the lung index in the Tamiflu-2 group was significantly lower (P <0.05) ,and the thy-mus index was significantly higher (P<0.05). The viral load was 0. 03 times that of the model-2 group. The expression levels of 13 inflammatory factors were significantly different (P < 0. 05). Conclusions The symptoms of the mice in Scheme 2 are more obvious and stable after exposure. After administration, the lung inflammation damage is alleviated. Considering the latency, drug intervention is in line with the drug indications when the model animals show symptoms. It will be more reasonable and accurate whether in the model evaluation or drug evaluation.

Targeting fibroblast activation protein inhibits endothelial-mesenchymal transition by affecting cancer-associated fibroblasts derived exosomes / 中国药理学通报

Aim To investigate whether targeted inhibition of fibroblast activation protein (FAP) can inhibit the endothelial-to-mesenchymal transition (EndMT) of vascular endothelial cells by affecting exosomes (Exo) of cancer-associated fibroblasts (CAFs) and explore the underlying mechanisms. Methods Primary CAFs and peri-tumor fibroblasts (PTFs) were obtained from lung cancer and peri-cancer tissues, and CAFs-exo and PTFs-exo were collected from culture medium, respectively. Exosomes from CAFs treated with specific FAP inhibitor (3.3 nmol • L-

The Circadian System Is Essential for the Crosstalk of VEGF-Notch-mediated Endothelial Angiogenesis in Ischemic Stroke / 神经科学通报·英文版

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.

Intrauterine Device Totally Embedded in the Bladder Wall:Report of One Case / 中国医学科学院学报

Intrauterine device(IUD)migrating to the bladder is rare,especially the migration far away from the uterus into the bladder wall.Due to no obvious clinical symptom in the early stage and being far away from the uterus,the IUD totally embedded in the bladder wall is prone to misdiagnosis and delay in treatment.We reported one case of such migration,aiming to improve the clinical management of the IUD totally embedded in the bladder wall.

Adaptation of the electron transport chain improves the biocatalytic efficiency of progesterone 17α hydroxylation / 生物工程学报

17α hydroxylase is a key enzyme for the conversion of progesterone to prepare various progestational drug intermediates. To improve the specific hydroxylation capability of this enzyme in steroid biocatalysis, the CYP260A1 derived from cellulose-mucilaginous bacteria Sorangium cellulosum Soce56 and the Fpr and bovine adrenal-derived Adx4-108 derived from Escherichia coli str. K-12 were used to construct a new electron transfer system for the conversion of progesterone. Selective mutation of CYP260A1 resulted in a mutant S276I with significantly enhanced 17α hydroxylase activity, and the yield of 17α-OH progesterone reached 58% after optimization of the catalytic system in vitro. In addition, the effect of phosphorylation of the ferredoxin Adx4-108 on 17α hydroxyl activity was evaluated using a targeted mutation technique, and the results showed that the mutation Adx4-108T69E transferred electrons to S276I more efficiently, which further enhanced the catalytic specificity in the C17 position of progesterone, and the yield of 17α-OH progesterone was eventually increased to 74%. This study provides a new option for the production of 17α-OH progesterone by specific transformation of bacterial-derived 17α hydroxylase, and lays a theoretical foundation for the industrial production of progesterone analogs using biotransformation method.