Genetic evidence strengthens the connection between gut microbiota and gingivitis: a two-sample Mendelian randomization study.

Introduction: The oral cavity and gut tract, being interconnected and rich in microbiota, may have a shared influence on gingivitis. However, the specific role of distinct gut microbiota taxa in gingivitis remains unexplored. Utilizing Mendelian Randomization (MR) as an ideal method for causal inference avoiding reverse causality and potential confounding factors, we conducted a comprehensive two-sample MR study to uncover the potential genetic causal impact of gut microbiota on gingivitis. Methods: Instrumental variables were chosen from single nucleotide polymorphisms (SNPs) strongly associated with 418 gut microbiota taxa, involving 14,306 individuals. Gingivitis, with 4,120 cases and 195,395 controls, served as the outcome. Causal effects were assessed using random-effect inverse variance-weighted, weighted median, and MR-Egger methods. For replication and meta-analysis, gingivitis data from IEU OpenGWAS were employed. Sensitivity analyses included Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. This study aimed to assess the genetic correlation between the genetically predicted gut microbiota and gingivitis using linkage disequilibrium score regression (LDSC). Results: Three gut microbiota taxa (class Actinobacteria id.419, family Defluviitaleaceae id.1924, genus Defluviitaleaceae UCG011 id.11287) are predicted to causally contribute to an increased risk of gingivitis (P< 0.05). Additionally, four gut microbiota taxa (class Actinobacteria id.419, genus Escherichia Shigella id.3504, genus Ruminococcaceae UCG002 id.11360) potentially exhibit inhibitory causal effects on the risk of gingivitis (P< 0.05). No significant evidence of heterogeneity or pleiotropy is detected. Our findings indicate a suggestive genetic correlation between class Actinobacteria id.419, class Bacteroidia id.912, family Defluviitaleaceae id.1924, genus Escherichia Shigella id.3504 and gingivitis. Conclusion: Our study establishes the genetic causal effect of 418 gut microbiota taxa on gingivitis, offering insights for clinical interventions targeting gingivitis. Subsequent research endeavors are essential to corroborate the findings of our present study.

Evaluation of the immunization effectiveness of bOPV booster immunization and IPV revaccination.

To provide a basis for further optimization of the polio sequential immunization schedule, this study evaluated the effectiveness of booster immunization with one dose of bivalent oral poliovirus vaccine (bOPV) at 48 months of age after different primary polio immunization schedules. At 48 months of age, one dose of bOPV was administered, and their poliovirus types 1-3 (PV1, PV2, and PV3, respectively)-specific neutralizing antibody levels were determined. Participants found to be negative for any type of PV-specific neutralizing antibody at 24, 36, or 48 months of age were re-vaccinated with inactivated polio vaccine (IPV). The 439 subjects who received a bOPV booster immunization at the age of 48 months had lower PV2-specific antibody levels compared with those who received IPV. One dose of IPV during basic polio immunization induced the lowest PV2-specific antibody levels. On the basis of our findings, to ensure that no less than 70% of the vaccinated have protection efficiency, we recommend the following: if basic immunization was conducted with 1IPV + 2bOPV (especially Sabin strain-based IPV), a booster immunization with IPV is recommended at 36 months of age, whereas if basic immunization was conducted with 2IPV + 1bOPV, a booster immunization with IPV is recommended at 48 months of age. A sequential immunization schedule of 2IPV + 1bOPV + 1IPV can not only maintain high levels of antibody against PV1 and PV3 but also increases immunity to PV2 and induces early intestinal mucosal immunity, with relatively good safety. Thus, this may be the best sequential immunization schedule for polio in countries or regions at high risk for polio.

Application of OrVil TM in patients with recurrent or denovo esophagogastric junction cancer / 中华普通外科杂志

Objective:To investigate the effect of transorally inserted anvil (OrVil TM) in patients with relapsed or denovo carcinoma at the esophagogastric junction. Methods:The clinical data of 60 patients who underwent radical intent resection for locally relapsed or denovo esophagogastric junction adenocarcinoma at Zhengzhou University Cancer Hospital from Jan 2011 to Jun 2021 were retrospectively analyzed. The patients were divided into two groups according to whether transorally inserted anvil was used. Twenty-six patients who had used the system were assigned to the experimental group. Thirty-four patients without transorally inserted anvil were set to control group.Results:The incisor distance of the experimental group was shorter than that of the control group [36(34-40)cm vs. 39(36-41)cm, Z=-4.948, P<0.05]. Operation time in experimental group was 177 (145-260) min, compared to control group of 172 (140-225) min ( Z=-0.735, P=0.463). Intraoperative blood loss was 200 (100-900) ml in the experimental group and 300 (100-800) ml in the control group ( Z=-1.244, P=0.213). Postoperative upper margin distance of the experimental group was (3.6±1.7) cm compared to control group of (1.8±1.1) cm ( t=-0.735, P<0.01). The positive rate of margin in the experimental group was 4% vs. 15% in the control group ( χ2=1.931, P=0.165). The length of postoperative hospital stay in the experimental group was (18.6±5.2) d vs. (20.5±4.7) d ( t=-1.455, P=0.151). Surgery-related complications developed in 19% in the experimental group vs. 27% in the control group ( P>0.05). Conclusion:The application of the transorally inserted anvil in the operation of patients with locally relapsed or denovo esophagogastric junction cancer after initial operation reduces the difficulty of operation and decreases the positive rate of margin.

Surgical treatment of duodenal fistula with intra-abdominal infection / 中华普通外科杂志

Object:To explore surgical treatments for duodenal fistula with intra-abdominal infection.Methods:The data of 19 patients with duodenal fistula treated at the Affiliated Tumor Hospital of Zhenzhou University between Jan 2015 and Dec 2021 were analyzed retrospectively. Surgery is performed with duodenostomy or modified duodenal shunt procedures.Result:All patients were accompanied by intra-abdominal infection, including 9 duodenal stump fistulas. All patients successfully completed the operation,11cases underwent duodenostomy, 8 case underwent modified duodenal shunt procedures. operating time was 110(60-140)min, postoperative hospitalization time was 29(9-103)d. Two patients died postoperatively. Fistula heals in other patients.Conclusion:Surgical intervention for duodenal fistula should focus on controlling the source of infection, strengthening intestinal and abdominal drainage, and reducing postoperative complications.

Study on the reasons of the interruption of Chinese residents' physical fitness behavior / 中华行为医学与脑科学杂志

Objective:To discusses the formation mechanism and influencing factors of sports fitness behavior interruption.Methods:From January 1st to April 30th in 2015, the adults aged 20 and above in the national survey of fitness activities were selected as the research objects to analyze the reasons for the interruption of fitness behavior of Chinese residents, including 32 877 people with fitness habits and 5 152 people with interrupted fitness habits.SPSS 19.0 and AMOS 17.0 software were used to process the data.The chi-square test was used to analyze the characteristics and changing trend of people who interrupted physical fitness behavior.Correlation analysis and factor analysis were used to categorize public factors of residents' physical fitness behavior characteristics.Validating factor analysis and path analysis were used to analyze the main reasons affecting the disruption of residents' physical fitness behaviors.Results:The fitness interruption behavior among Chinese residents were statistically significant different in terms of age, gender, and habitation( χ2=2.791, 199.435, 12.402, all P<0.05). The highest percentage of fitness interruptions was observed among residents aged 20-39 (19.1%) in China, women (16.2%) were higher than men (15.5%), and urban (16.4%) were higher than rural (14.9%). Factor classification and model analysis showed that the occurrence of disruptions in physical fitness behavior among Chinese residents was influenced by a combination of health factors( β=0.52), social environment( β=0.57), psychological factors( β=0.42), and fitness behavior environment( β=0.22). Conclusion:The occurrence of disruption of physical fitness behavior of our residents is mainly influenced by the combination of health factors, psychological factors, social environment, and fitness behavior environment.

Sports and health integration: logic, dilemma and alleviation / 中华行为医学与脑科学杂志

By combing out the historical development logic of sports and health integration and the current development achievement, the underlying logic of sports and health integration is described systematically in multiple dimensions, and the prominent dilemmas in development are analyzed as follows: lack of residents' health literacy, excessive dependence on medical treatment, low bridging of talent team construction, lack of the guidance of funds centralization, insufficient financial support, imperfect management system and mechanism, and unspecific departmental collaboration.The strategies for solving the problems are as follows: strengthening the integration of sports science and clinical medicine, consolidating the technical integration of sports prescription and clinical standardization process, further improving the business integration of exercise intervention and clinical treatment, and enhancing the industrial integration of sports products and medical treatment.

Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1Α pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.

The pregnancy outcomes of day-5 poor-quality and day-6 high-quality blastocysts in single blastocyst transfer cycles / 대한생식의학회지

Objective@#This study compared the outcomes of single blastocyst transfer cycles, using day- 5 poor-quality blastocysts and day-6 high-quality blastocysts. @*Methods@#We analyzed 462 frozen-thawed embryo transfer (FET) cycles performed at our center from January 2014 to December 2019. The cycles were divided into two groups: a day-5 poor-quality blastocyst transfer group (group A) and a day-6 high-quality blastocyst transfer group (group B). The clinical outcomes were tested. @*Results@#In groups A and B, respectively, the clinical pregnancy rate (CPR; 61.65% vs. 67.17%, p=0.258), implantation rate (IR; 61.65% vs. 67.17%, p=0.258), and live birth rate (LBR; 69.51% vs. 77.83%, p=0.134) showed no significant differences. Moreover, when day-3 embryo quality was considered, the CPR, IR, and LBR were also similar in group A and group B (p>0.05). @*Conclusion@#The clinical outcomes of day-5 poor-quality blastocysts and day-6 high-quality blastocysts were similar, suggesting that the developmental speed of the embryo might be more important than embryo quality for the clinical outcomes of single blastocyst transfer in FET cycles.

Advances in colonic manometry in adults with colonic motility disorders / 中华胃肠外科杂志

In recent years, colonic manometry has been gradually introduced into clinical practice. It helps clinicians to gain a better understanding of the physiology and pathophysiology of colonic contractile activity in healthy adults and patients with colonic dysfunction. More and more patterns of colonic motility are being discovered with the help of colonic manometry. However, the clinical significance of these findings still needs to be further investigated. This review enhances our understanding of colonic motility and the current state of development and application of colonic manometry, as well as the limitations, future directions and potential of the technique in assessing the impact of treatment on colonic motility patterns, by analyzing and summarizing the literature related to colonic manometry.

Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway / 中国中药杂志

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

The impact of carbon nanoparticle tracer on the harvested number of lymph nodes in obese gastric cancer patients undergoing radical resection / 中华普通外科杂志

Object:To investigate the impact of carbon nanoparticle tracing on the number of lymph nodes harvested in obese patients during radical gastrectomy for gastric cancer.Methods:Clinical data of 127 patients undergoing D 2 radical gastrectomy in the Affiliated Tumor Hospital of Zhengzhou University from Jan 2015 to Dec 2019 were retrospectively analyzed. According to whether the patients were injected with carbon nano particles during operation, they were divided into two groups: 64 patients without carbon nano particles during operation served as control group; 63 patients with carbon nano particles were included into experimental group. Results:The operation time of the control group was (160±31) min and that of the experimental group was (168±28) min ( t=-1.521, P=0.445). Intraoperative blood lose in the control group was (234±82) ml and that in the experimental group was (238±84) ml ( t=-0.295, P=0.846). The number of lymph nodes harvested in the first station, in the second station, the number of total lymph nodes and the number of lymph nodes with diameter <5 mm in the control group were less than those in the experimental group(10.4±3.8 vs. 24.5±10.6, t=-10.054),(6.6±2.8 vs. 16.8±7.3, t=-10.381),(17.1±6.4 vs. 41.2±17.6, t=-10.293),(3.9±2.5 vs. 21.2±9.1, t=-14.662) (all P<0.05), while the number of positive lymph nodes was not statistically different between the two groups all (5.9±6.2 vs. 4.2±3.4, t=-1.963, P>0.05). Black staining of lymph nodes in nano carbon group: 1 542 black stained lymph nodes were detected in the experimental group, the black staining rate of lymph nodes was 59.44% (1 542/2 594). Conclusion:Intraoperative application of carbon nanoparticles can significantly increase the number of harvested lymph nodes in obese (BMI≥25 kg/m 2) gastric cancer patients after radical resection.

Changes of cognitive function in non-fatal drowning rats after blast-induced traumatic brain injury / 中华创伤杂志

Objective:To investigate the changes of cognitive function in non-fatal drowning rats after blast-induced traumatic brain injury (bTBI).Methods:Eighty SD rats were divided into normal group, bTBI group, drowning group and bTBI plus drowning group according to the random number table, with 20 rats per group. Rats in normal group were not injured. In bTBI group, bTBI was established in a BST-I biological shock tube with a pressure of 4.0 MPa in the driving section. In drowning group, rats were subjected to non-fatal drowning by falling into the water with temperature of 18 ℃ and depth of 30 cm from the height of 1 m and were taken out quickly after swimming to exhaustion. After being injured in a biological shock tube, rats in bTBI plus drowning group were immediately forced to drowning using the same method. On day 3 post-injury, the neurocognitive function was evaluated by elevated plus maze and Morris water maze tests. Morphological changes of neurons in CA1 and CA3 regions of hippocampus were observed by Nissl staining, and the number of surviving neurons were counted. The concentrations of hippocampal neurotransmitters glutamate, γ-aminobutyric acid (GABA), glycine and endoplasmic reticulum stress (ERS) related glucose-regulated protein 78 (GRP78) and caspase-12 were examined by ELISA analysis. Levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein (Bax) and caspase-3 were detected by Western blotting. The ratio of Bcl-2 to Bax was calculated as well.Results:In elevated plus maze test, the percentage of open arm entry and number of head-dipping behaviour were decreased in bTBI plus drowning group compared with normal and bTBI groups at 3 days after injury ( P<0.05 or 0.01), with no statistical difference from those in drowning group ( P>0.05). The number of head-dipping behaviour in drowning group was lower than that in bTBI group ( P<0.05). In Morris water maze test, bTBI plus drowning group showed increased target latency on the third and fourth days of spatial acquisition training and decreased number of crossing the target area and percentage of swimming time in the target quadrant during probe trials as compared with normal group ( P<0.05 or 0.01), but there was no statistical difference among bTBI, drowning and normal groups (all P>0.05). Nissl staining showed that the neurons in the CA1 and CA3 regions of hippocampus in normal group were arranged neatly with clear Nissl bodies at 3 days after injury, while the other groups showed different degrees of injury. In contrast with normal group, the neurons in the CA1 and CA3 regions of hippocampus in all other groups were decreased with the lowest number in bTBI plus drowning groups ( P<0.05 or 0.01). In ELISA analysis, the level of hippocampal glutamate in bTBI plus drowning group was higher than that in all other groups at 3 days after injury and the level in bTBI injury and drowning groups was higher than that in normal group ( P<0.05 or 0.01); the level of hippocampal glycine in bTBI plus drowning group was lower than that in normal group ( P<0.05), but there was no statistical difference among bTBI, drowning or normal groups (all P>0.05); the concentration of hippocampal GABA had no statistical difference among all groups (all P>0.05). In addition, the concentration of GRP78 in bTBI injury, drowning and bTBI injury plus drowning groups were increased compared with normal group ( P<0.05 or 0.01), but did not statistically differ from each other (all P>0.05). The concentration of caspase-12 in drowning and bTBI plus drowning groups were increased compared with normal group ( P<0.05 or 0.01), but was not statistically different from each other ( P>0.05), and its concentration in bTBI plus drowning group was increased compared with bTBI group ( P<0.05). In Western blotting, the level of Bcl-2 in bTBI plus drowning group was decreased compared with all other groups at 3 days after injury, and the level in bTBI and drowning groups were decreased compared with normal group, but a much lower level was observed in drowning group than that in bTBI group ( P<0.05 or 0.01); the level of Bax in bTBI plus drowning group was increased compared with all other groups at 3 days after injury, and the level in drowning group was increased compared with normal group ( P<0.05 or 0.01), with no statistical difference between bTBI and drowning groups ( P>0.05). The ratio of Bcl-2 to Bax in bTBI plus drowning group was decreased compared with all other groups, while the ratio in bTBI and drowning groups were decreased compared with normal group, showing a much lower level in drowning group than that in bTBI group ( P<0.05 or 0.01). Also, the level of caspase-3 in drowning and bTBI plus drowning groups were increased compared with normal and bTBI groups ( P<0.05 or 0.01), but there was no statistical difference between drowning and bTBI plus drowning groups ( P>0.05). Conclusions:Non-fatal drowning can aggravate hippocampal neuron damage in bTBI rats and cause memory, emotion and other cognitive dysfunction. The mechanism may involve the imbalance of hippocampal neurotransmitters glutamate and glycine, which activates the downstream pro-apoptotic pathway through ERS in the early stage of injury to induce hippocampal neuron apoptosis.

Research progress on the relationship between exosomes and pain / 中国医师杂志

Exosomes are extracellular microbubbles related to intercellular communication, which have the ability to transport and transfer biological macromolecules. Pain will lead to a sharp decline in the quality of life of patients, and will give patients and society a heavy medical burden. More and more evidences show that the exosomes plays an important role in the pathological process of pain related diseases.Summarizing the exosomes and the biomolecules carried by them under different pain conditions, and identifying the specific exosomes related to the pain state will be helpful for early diagnosis and treatment of pain related diseases. In addition, the ability of exosomes to transmit information and its widespread characteristics in the body indicate that they have broad prospects as a new diagnosis and treatment tool in the field of pain. A better understanding of the relationship between the exosomes and pain will provide a novel and promising treatment for patients with pain.

Study on the differentiation of rat bone marrow mesenchymal stem cells into islet-like cell masses under co-culture conditions / 中华胰腺病杂志

Objective:To examine the possibility of the differentiation into islet-like cell clusters from the co-culture system of bone marrow mesenchymal stem cells (BMSCs) and islet cells.Methods:Rat BMSCs from the femur and tibia of Wistar rats were isolated and purified taken under aseptic conditions; the surface markers CD 44 and CD 90 expressions of BMSCs were detected by flow cytometry; and alizarin red staining and oil red O staining were used to identify the cells induced in the osteogenic direction and adipogenic direction, respectively. Rat islet cells from the pancreas of Wistar rats were isolated and purified; and dithiazone staining was performed for validation. The basal insulin level of the culture was detected by ELISA method. 5.6mmol/L (low glucose) and 25.0 mmol/L (high glucosa) glucose were added to the culture, respectively, and insulin release was detected by ELISA. 5-generation BMSCs and islet cells were collected and divided randomly into stem cell culture alone group (stem cell group), stem cell-islet co-culture group (co-culture group), and islet culture alone group (islet group). The morphological changes of BMSCs during co-culture were observed using an inverted phase contrast microscope; basal insulin secretion and insulin secretion stimulated by low and high glucose were tested by ELISA. Insulin protein expression in induced islet-like cell masses in co-culture group were detected by immunocytochemical staining. The ultrastructure of islet-like cells was observed by using transmission electron microscopy. Results:The positive rates of CD 44 and CD 90 were 99.48% and 99.50%, respectively; BMSCs were induced the formation of multiple calcium nodules outside the differentiation cells in the osteogenic direction, and many lipid droplets in the cytoplasm of differentiated cells in the adipogenic direction. Dithiazone staining showed that β cells in pancreatic islet were brown red and about 450 islets could be obtained per pancreas with a mean purity up to 80%. The insulin release in the low sugar group and the high sugar group were (7.105±1.551) mIU/ml and (20.231±1.592) mIU/ml, respectively, with a statistically significant difference ( P<0.05). It can be seen that local stem cells began to gather and grow upward into small clumps in the budding manner until finally forming a spherical islet-like cell cluster structure after 7 days of culture in the co-culture group. The basal insulin secretion in the stem cell group was <0.5 mIU/L. In the islet group, insulin secretion peaked on the 5th day and then gradually decreased to about 20% of the highest value on the 13th day. The insulin level of the co-culture group peaked on the 5th day, and the 13th day remained at about 40% of the peak level. There were statistically significant differences on basal insulin secretion on the 8th, 10th and 13th day between islet group and co-culture group (all P value >0.05). There was no statistically significant difference between the insulin release by islet in islet group under the stimulation of low and high sugar and that by islet-like cell cluster in co-culture group. There were a large number of brownish-yellow granules in the islet-like cell clusters after the co-culture for 14 days; and there were more secretory granules and coarse endoplasmic reticulum in the ultrastructure, showing more active protein secretion functions. Conclusions:The co-culture system of BMSCs and islet cells could induce BMSCs into differentiating into islet-like cell clusters, which can express insulin protein and had relatively mature function of insulin secretion.

Sweroside Effectively Protects Against Ischemia/Reperfusion Injury by Regulating Excitation-contraction Coupling / 中国实验方剂学杂志

ObjectiveTo explore the effect of sweroside on the protection of cardiac systolic/diastolic function during ischemia/reperfusion （I/R） injury. MethodTwenty-four healthy male SD rats were randomly divided into control group， model group， 10 μmol·L-1 sweroside group and 1 μmol·L-1 digoxin group. The I/R injury was modeled by Langendorff and ligation of the left anterior descending coronary artery. The infarct size in each group was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining and hemodynamic parameters such as left ventricular diastolic pressure （LVDP）， left ventricular end-diastolic pressure （LVEDP）， left ventricular end-systolic pressure （LVESP）， maximum rate of rising of left ventricular pressure （+dp/dtmax） and maximum rate of decreasing of left ventricular pressure （-dp/dtmax） of rat isolated heart were detected by Powerlab. In addition， neonatal rat cardiomyocytes （NRCMs） were isolated and randomly divided into control group， model group， 1 μmol·L-1 sweroside group and 10 μmol·L-1 sweroside group. Hypoxia/reoxygenation （H/R） injury model was established. Cardiac systolic function and calcium transients were examined by multi-functional cell imaging analyzer and laser confocal microscope. Furthermore， real-time polymerase chain reaction（Real-time PCR） was used to verify the mRNA expression of excitation-contraction coupling genes such as L-type calcium channel （Cacnb2）， cytochrome c oxidase subunit 6A2 （Cox6a2）， troponin （Tnnc1， Tnni3， Tnnt2）， actin （Actc1）， and myosin （Myh6， Myl2， Myl4） according to the results of previous transcriptome sequencing and literature investigation. Differentially expressed genes were subjected to cluster analysis. ResultCompared with the conditions in the control group， increased cardiac infarction size （P<0.01） and LVEDP （P<0.01） and decreased LVDP （P<0.01） and LVESP （P<0.05） were observed in the model group， with +dp/dtmax of increasing trend while -dp/dtmax decreasing. Moreover， the cell viability， heart rate and contraction amplitude of NRCMs was reduced （P<0.01）， while the contraction duration， time to peak and relaxation time was elevated （P<0.01） in the model group. Interestingly， sweroside could reverse these indicators （P<0.05）. In addition， the expression of Cacnb2， Cox6a2， Tnnc1， Tnni3， Tnnt2， Actc1， and Myh6， Myl2， and Myl4 was down-regulated in the model group （P<0.05， P<0.01）， but sweroside could up-regulate the expression of the above genes （P<0.05）. ConclusionSweroside effectively regulated Ca2+ level in NRCMs， enhanced cardiac systolic function， and protected against H/R injury by regulating excitation-contraction coupling.

Integrating systematic pharmacology-based strategy and experimental validation to explore mechanism of Tripterygium glycoside on cholangiocyte-related liver injury / 中草药·英文版

Objective: Tripterygium glycoside (TG) is widely used in clinical practice for its multiple bioactivities including anti-inflammatory and immunosuppressive effects. However, emerging studies have frequently reported TG-induced adverse reactions to multiple organs, especially liver. Here, this study aimed to investigate the mechanism of liver damage induced by TG and explore representative components to reflect TG hepatotoxicity. Methods: Network pharmacology was used to determine the potential targets of bile duct injury caused by TG. Next, the hepatotoxic effects of TG, triptolide (TP) and celastrol (CEL) were investigated and compared in vivo and in vitro. Liver function was determined by measuring serum transaminase and histopathology staining. The cell proliferation and apoptosis were determined by cell viability assay, scratch assay and flow cytometry. The expression of gene of interest was determined by qPCR and Western blot. Results: Based on the network pharmacological analysis of 12 bioactive ingredients found in TG, a total of 35 targets and 15 pathways related to bile duct injury were obtained. Both TG and TP resulted in cholangiocyte damage and liver injury, as illustrated by increased levels of serum transaminase and oxidative stress, stimulated portal edema and lymphocytic infiltration and decreased expression of cholangiocyte marker, cytoskeletal 19. In addition, TG and TP inhibited cell proliferation and migration, arrested cell cycle and promoted Caspase-dependent apoptosis of cholangiocytes via suppressing the phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and protein kinase B (AKT). While, CEL at equivalent dosage had no obvious hepatotoxicity. Conclusion: We revealed that TG-stimulated liver injury was specifically characterized by cholangiocyte damage and TP might be the decisive ingredient to reflect TG hepatotoxicity. Our results not only provide novel insights into the mechanism underlying the hepatotoxicity effects of TG but also offer reference for clinical rational use of TG.

Scarf osteotomy combined with soft tissue balance release for severe hallux valgus / 中国骨伤

OBJECTIVE@#To explore clinical effect of Scarf osteotomy combined with soft tissue balance in treating severe hallux valgus.@*METHODS@#Totally 38 patients(50 feet) with severe hallux valux who underwent Scarf osteotomy combined with soft tissue balance surgery from June 2019 to June 2021 were retrospectively analyzed, aged from 29 to 64 years old with an average of(54.7±6.8) years old; 26 feet on the left side and 24 feet on the right side;the courses of disease ranged from 5 to 23 years with an average of (12.4±3.9) years. Hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) were compared before and after operation, and postoperative complications was observed. American orthopedic foot ankle society(AOFAS) score before operation and final follow-up was used to evaluate recovery of forefoot function, and visual analogue scale (VAS) was used to evaluate pain relief.@*RESULTS@#Thirty-eight patients (50 feet) were followed up from 15 to 23 months with an average of (18.3±3.2) months. Preoperative HVA, IMA and DMAA were (44.61±3.92)°, (18.74±2.51)°, (12.85±2.11)°, and improved to (13.45±2.13)°, (7.83±1.36)°, (7.03±1.39)°at final follow-up, which had statistical differneces(P<0.05). No delayed union or nonunion of osteotomy end, fracture or loosening of internal fixation, hallux varus occurred. VAS and AOFAS score improved from (6.81±2.14), (43.6±8.4)points before operation to (1.97±0.78), (87.6±5.2) points at final follow-up, which had statistical difference(P<0.01). According to AOFAS at final follow-up, 20 feet got excellent result, 28 feet good and 2 feet moderate.@*CONCLUSION@#Scarf osteotomy combined with soft tissue balance release for severe hallux valgus has good stability and corrective effect, but learning curve and postoperative complications should be paid attention.

Research progress of lncRNA regulating miRNA in osteoarthritis / 中国综合临床

Non-coding RNAs (ncRNAs), which are thought to regulate articular cartilage through endochondral osteogenesis, consist of mRNA-interfering complementary RNA (miRNA) and long non-coding RNAs (lncRNA). More and more experimental evidence reveals the role of ncRNAs in chondrocyte differentiation and the pathogenesis of several skeletal diseases, including osteoarthritis. In the past few years, increasingly sophisticated DNA sequencing methods and a large number of sepigenetic modifications have greatly contributed to our understanding of the pathophysiological mechanisms of osteoarthritis. Recent studies have revealed that RNA interacts with RNA-binding proteins, regulates gene transcription and protein translation, and is involved in various pathological processes in OA, promising to be a therapeutic target for osteoarthritis.

A Nomogram model involving preoperative inflammatory markers for predicting postoperative overall survival in patients with stage Ⅰ-Ⅲ gastric cancer / 中华普通外科杂志

Objective:To establish a nomogram to predict overall survival of patients with stage Ⅰ-Ⅲ gastric cancer (GC) based on preoperative inflammatory markers.Methods:Clinicopathological and follow-up data of 1 035 patients with stage Ⅰ-Ⅲ gastric cancer operated at He'nan Cancer Hospital between May 2015 and Oct 2016 were retrospectively collected. A nomogram was established based on prognostic factors. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the performance of the model according to differentiation, calibration and clinical utility.Results:A total of 1 035 patients were enrolled . The median follow-up time was 41.9 months; According to the optimal cutoff value, 170 were with elevated neutrophil-to-lymphocyte ratio (NLR) and 865 with a reduced　ratio; 562 in elevated platelet-to-lymphocyte ratio (PLR) vs. 473 in the reduced group; fibrinogen/albumin ratio (FAR) elevated in 108 group vs. 972 in the reduced group; 180 in the prognostic nutritional index score (PNI) elevated group and 855 in the reduced group. Two hundred and sixty-seven patients were categorized at stage Ⅰ, 334 at stage Ⅱ ,434 at stage Ⅲ. Multivariate regression analysis showed tumor location, vascular tumor thrombus, pTNM stage, FAR, PNI and NLR were independent prognostic factors (all P<0.05). The C-index of the nomogram was 0.723 (95% CI: 0.710 -0.736) and had better clinical utility than the American Joint Committee on Cancer (AJCC) 8th TNM staging system 0.693 (95% CI, 0.681 -0.705). The calibration curve of the nomogram showed that the predicted survival rate was consistent with the actual survival rate in GC patients. Compared to AJCC 8th pTNM staging system, the DCA curve indicate that the nomogram has a higher net income. Conclusion:The nomogram predicting overall survival of patients with stage Ⅰ-Ⅲ gastric cancer is established and verified , which provides better individual prediction than TNM staging system.