ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Objective To explore the effects of Buyang Huanwu Decoction on neuronal cell apoptosis after cerebral ischemia based on mediating Cav1 in regulating Wnt pathway.Methods Male wild-type(WT)and Cav1-/-(KO)C57BL/6 mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group(18.5 g/kg).Cerebral ischemia model was prepared using middle cerebral artery occlusion method,and drug intervention was given for 14 days.Neurobehavioral score was performed,HE staining was used to observe the morphology of ischemic cortical area of brain tissue,TUNEL staining was used to detect neuronal apoptosis in ischemic cortical area,immunohistochemistry was used to detect the expressions of apoptosis related proteins and Wnt1,glycogen synthase kinase 3β(GSK3β)and β-catenin protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurobehavioral score of the model group mice significantly increased,neuronal cells in the ischemic cortical area showed vacuolar changes,with nuclear condensation and widened intercellular spaces,the apoptosis rate of nerve cells significantly increased,with increased expressions of Bax,GSK3β and decreased expressions of Bcl-2,Wnt1 and β-catenin(P<0.01).Compared with the same genotype model group,the neurobehavioral score of mice in Buyang Huanwu Decoction group were significantly decreased,the pathological damage of the ischemic cortical area improved,the apoptosis rate of nerve cells decreased,the expressions of Bax and GSK3β decreased,and the expressions of Bcl-2,Wnt1 and β-catenin increased(P<0.01).Compared with the WT model group,the KO model group showed an increase in neurobehavioral score,aggravated damage in ischemic cortical area,significantly increased neuronal apoptosis rate,and increased expression of GSK3β(P<0.05).Compared with the WT Buyang Huanwu Decoction group,the KO Buyang Huanwu Decoction group showed an increase in neurobehavioral score,aggravated damage in ischemic cortical area,significantly increased neuronal apoptosis rate,increased expressions of Bax and GSK3β,and decreased expressions of Bcl-2,Wnt1 and β-catenin(P<0.01).Conclusion Buyang Huanwu Decoction can inhibit neuronal cell apoptosis after cerebral ischemia,and its mechanism may be related to regulating the expressions of apoptosis-related proteins by mediating Cav1 to regulate the Wnt signaling pathway.

Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

Objective To explore the mechanism of Buyang Huanwu Decoction against cerebral ischemia-reperfusion injury in rats by regulating lipid metabolism through the cAMP/PKA/PPARγ pathway.Methods 60 rats were randomly divided into sham operation group(Sham),model group(Model),Buyang Huanwu Decoction low-dose group(BHD-L),Buyang Huanwu Decoction medium-dose group(BHD-M),Buyang Huanwu Decoction high-dose group(BHD-H)and Butylphthalide group(NBP).The cerebral ischemia-reperfusion model was prepared by transient middle cerebral artery embolization.The BHD low-,medium-and high-groups were given different doses of Buyang Huanwu Decoction(6.413,12.825,25.65 g·kg-1)by intragastric administration.The NBP group was administered with Butylphthalide(54 mg·kg-1).The sham operation group and the model group were administered with an equal volume of distilled water,all given for 14 days.The rats were subjected to neurobehavioral scoring.HE staining was used to observe brain pathological changes,and the kit was used to detect the levels of phosphocholine(PC),phosphatidylethanolamine(PE),diacylglycerol(DAG),and free fatty acid(FFA)on the ischemic side.RT-qPCR and Western Blot were applied to detect the mRNA and protein expressions of cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),and peroxisome proliferator-activated receptor γ(PPARγ).Results Compared with the sham group,the neurological deficit score was significantly increased(P＜0.01),pathomorphological damage in ischemic cortex was found,the contents of PC and PE were reduced,the contents of DAG and FFA were increased(P＜0.01),and cAMP mRNA expression increased(P＜0.05)in the model group.Compared with the model group,the neurological deficit score of the BHD-L group was decreased(P＜0.05),and the neurological deficit score of the BHD-M,BHD-H and NBP groups was significantly decreased(P＜0.01),the cells in each treatment group were regularly arranged,the intercellular spaces were reduced,and the normal cells were increased.PC and PE were significantly increased,DAG and FFA were significantly decreased(P＜0.01)in the BHD-M,BHD-H and NBP groups.PC was increased,FFA and DAG were decreased in the BHD-L group(P＜0.05,P＜0.01).The mRNA level of PPARγ was increased in the BHD-L group(P＜0.05),and the mRNA and protein levels of cAMP,PKA,and PPARγ were increased in the other treatment groups(P＜0.05,P＜0.01).Conclusion Buyang Huanwu Decoction has a neuroprotective effect on cerebral ischemia-reperfusion injury rats,and its mechanism may be related to regulating the expression of key factors in the cAMP/PKA/PPARγ signaling pathway and lipid metabolism.

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its hetero-geneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods: and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

Objective:To detect the incidence of muscle mass loss in the adults and explore its relevant influencing factors.Methods:A total of 1 503 participants aged between 18 and 65 years old were collected from the Department of Preventive Treatment of Disease and Health Management Center of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from March 2019 to October 2021. All subjects completed physical and laboratory examination and bioelectrical impedance analysis. According to the cutpoint of plasma triglycerides concentration≥1.7 mmol/L, waist circumference≥85 cm in men or≥80 cm in women, 1 503 subjects were divided into four groups: normal triglycerides and waist circumference group, normal waist circumference and hypertriglyceridemia group, abdominal obesity and normal triglycerides group, and hypertriglyceridemic-waist phenotype(HTWC) group. Subjects were also divided into 4 groups according to age. Skeletal muscle mass index(ASMI) was calculated according to the skeletal muscle mass of the limbs. Differences of the ASMI and other relevant indicators among the above four groups were analyzed, and body composition was compared among four age groups. Then explore whether HTWC phenotype was an independent risk factor for the occurrence of sarcopenia in different age groups of different gender.Results:The level of triglycerides, fasting blood glucose, systolic blood pressure, and diastolic blood pressure in HTWC group were higher than those in the normal group(all P<0.001). But the incidence of the muscle mass loss in the HTWC group was much lower than that in the other three groups( P<0.001). The incidence of muscle mass loss in overall subjects was 9.2%, in which man was 2.05 times higher than women(12.9% vs 6.3%). There is no statistically significant difference in the incidence of muscle mass loss between the 18-35 age group and the 56-65 age group. Multivariate logistic regression analysis revealed that body mass index, body fat percentage, bone mineral content were independent factors affecting muscle loss in 18-45 year-old adults. After adjustment for other risk factors, HTWC phenotype was still not an independent influencing factor of sarcopenia( OR=1.679, 95% CI 0.523-5.386, P=0.384). Conclusion:HTWC phenotype was not an independent influencing factor of sarcopenia. To prevent the occurrence of sarcopenia in middle-aged and young adults, in addition to assessing the muscle mass, attention should also be given to the measurement of body mass index, bone mineral content, and body fat percentage.

Objective:To investigate the effect of total saponins of Panax notoginseng (TSPN) on learning and memory of post-stroke depression (PSD) rats and its mechanism.Methods:Four-vessel occlusion method was used to build the rat stroke model and 7 days later these rats were given solitary breeding with chronic unpredictable mild stress (CUMS) to make depression model. Rats were randomly divided into Sham group ( n=10), Model group ( n=10), PSD group ( n=10) and TSPN group ( n=10). The rats in the Model group and PSD group were injected administered with equal volume of 0.9% saline 30 min post-brain ischemia, one injection per day for 30 days. while TSPN group were treated with TSPN. The dose of TSPN (75 mg/kg) was dissolved in 0.9% saline 10 g/L, once per day for 30 days. Then the learning and memory of rats were tested by Morris water maze.The protein levels of DCX and Nestin in the hippocampus were detected by Western blot. Furthermore, the DCX/Ki67 co-labeled cells in the SGZ of hippocampus were observed by the immunofluorescence. Results:The escape latency at the fifth day of PSD group((31.8±3.8)s) was longer than that in the Sham group((10.4±3.2)s) and Model group((19.8±3.7)s) ( t=9.23, 5.15; both P<0.05). The escape latency ((14.2±2.8)s) of TSPN group was shortened significantly than PSD group ( t=8.56, P<0.05). The times across the platform in the Sham group was (10.3±1.7), and the PSD group was (4.1±1.1), difference was statistically significant between two groups( t=11.24, P<0.05). The times across the platform (8.4±1.6) of TSPN group statistically increased compared with PSD group ( t=5.77, P<0.05). The protein levels of DCX and Nestin in the PSD group were (0.60±0.02), (0.58±0.03) respectively, and in the TSPN group were (1.07±0.07), (0.95±0.11) correspondingly, there were significant differences of the DCX, Nestin protein level between the two groups( t=20.22, 7.68, both P<0.01). Moreover, there was significant difference in the number of the DCX/Ki67cells in the hippocampus SGZ between the PSD group((16.2±2.8) /mm 2) and TSPN group ((21.2±3.1) /mm 2)( t=2.42, P<0.05). Conclusion:TSPN could improve the learning and memory of the rats with post-stroke depression through enhancing the hippocampus neurogenesis.

Objective To evaluate the relationship between anterior chamber angle and intraocular pressure (IOP) after laser peripheral iridotomy (LPI) treatment.Methods A retrospective cases control study was adopted.Fifty-eight patients (58 eyes) who were diagnosed as primary angle closure (PAC) were included in this study.Ultrasound biomicroscopy (UBM) parameters in angle opening distance (AOD),trabecular iris area (TISA) and angle recess area (ARA) examination were performed before LPI.The changes of intraocular pressure (IOP) were compared between different time-points (before and 1 hour,2 hours,8 hours,24 hours,2 weeks,6 months and 12 months after LPI).The patients were divided into IOP≤21 mmHg group (41 eyes) and IOP＞21 mmHg group (17 eyes) after LPI.Relationship between anterior chamber angle and IOP after LPI treatment was explored.This study was approved by Ethic Committee of the Henan Eye Institute and informed consent was obtained from each patient.Results The IOPs were increased in 1 hour,2 hours after LPI and lowered in 2 weeks,6 months,12 months after LPI compared with IOP before LPI,with significant differences between them (all at P＜0.01).Twelve patients suffered transient elevated IOP and recovered by self-healing or treatment.IOP of 4 patients were elevated after 6 months to 1 year follow-up.The IOPs in 2 weeks,6 months and 12 months after LPI were lowered compared with IOP before LPI,with significant differences between them (all at P＜0.01).The UBM parameters were significantly increased in 2 weeks,6 months,12 months after LPI in comparison with IOP before IPL (all at P＜0.01).IOP and UBM parameters values were significantly different between IOP＞21 mmHg group and ≤21 mmHg group after LPI.Regression analysis indicated that ARA750 (OR =0.75,P＜0.05) was correlated to the IOP after LPI rather than IOP before operation,AOD and TISA (P＞0.05).Conclusions ARA750 value is correlated with the IOP variations after LPI.UBM structured observation can improve the surgical successful rates and safty and prevent complications.

It is very significant that state trains rural-oriented medical students for grassroots health institutions.In combination with the characteristics of Chongqing rural-oriented medical students,the article analyzed and explained the reasons of building autonomous-cooperative learning model,discussed the connotation and the correlation theory of this model.Based on the above,the article designed and carried out autonomous-cooperative learning model,summarized the construction strategy from the aspects of organization and management mechanism,competitive and encouraging mechanism and evaluation mechanism,which explored a practical education pattern that suits rural-oriented medical students.

BACKGROUND:Primary human lung epithelial cel s are difficult to be isolated and cultured in vitro, which is characterized as limited sources, low cel viability, slow proliferation capacity, and lacking of differentiation capability.
OBJECTIVE:To establish an air-liquid interface model of lung epithelium by in vitro proliferation of human bronchiolar epithelial cel s, which is used for research on function of lung epithelial cel s.
METHODS:Primary human bronchiolar epithelial cel s were isolated using Pronase and DNase I combined digestive methods, and then proliferated using medium containing ROCK kinase inhibitor. The proliferated cel s were used for establishment of the air-liquid interface epithelium model. Cel differentiation was identified using scanning electron microscope, phase contrast microscope and immunofluorescent staining.
RESULTS AND CONCLUSION:The primary human bronchiolar epithelial cel s could be expanded successful y using medium containing ROCK kinase inhibitor, and the basal cel marker Cytokeratin14 was preferential y expressed in the proliferated cel population, indicating that these basal cel s might be the main subpopulation of human lung epithelial stem cel s. Subsequently, the proliferated cel s under the air-liquid interface could differentiate into ciliated cel s and non-ciliated column cel s. The results suggest that the proliferation and differentiation of human bronchiolar epithelial cel s were maintained in the presence of ROCK kinase inhibitor, and the air-liquid interface could promote the differentiation of human bronchiolar epithelial cel s.