Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

ObjectiveTo determine the syndrome of a rat model of follicular dysplasia induced by Tripterygium glycosides based on prescriptions and investigate the mechanism of traditional Chinese medicine intervention via the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/hypoxia-inducible factor-1 （HIF-1）/vascular endothelial growth factor （VEGF） pathway. MethodForty-eight rats with regular estrous cycles were randomly assigned into a normal group （n=8） and a modeling group （n=40）. The rats in the modeling group were administrated with Tripterygium glycoside suspension （75 mL·kg^-1） by gavage for 30 days. The modeled rats were assigned into model， Siwutang （3.69 g·kg^-1）， Youguiyin （3.11 g·kg^-1）， Zuoguiyin （7.29 g·kg^-1）， and Guishenwan （10.35 g·kg^-1） groups， with 8 rats in each group. The drug intervention lasted for 14 days. The changes of estrous cycle were detected by Pap staining， and a stereoscope was used to observe the morphology of the ovarian tissue. Hematoxylin-eosin staining was employed to observe the pathological changes and follicle count in the ovarian tissue. Enzyme-related immunosorbent assay （ELISA） was used to measure the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂） in the serum. Real-time fluorescence quantitative polymerase chain reaction and Western blot were employed to determine the mRNA and protein levels， respectively， of AMPK， mTOR， HIF-1， and VEGF in the ovarian tissue. ResultCompared with the normal group， the model group had a disordered estrous cycle， reduced secondary and mature follicles， increased atretic follicles， elevated FSH and LH levels， lowered E₂ level， up-regulated mRNA and protein levels of AMPK， and down-regulated mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with the model group， Guishenwan increased secondary and mature follicles， decreased atretic follicles， lowered the FSH and LH levels， elevated the E₂ level， down-regulated the mRNA and protein levels of AMPK， and up-regulated the mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with Guishenwan group， Siwutang， Youguiyin， and Zuoguiyin decreased mature follicles， increased atretic follicles （P<0.01）， elevated the LH （P<0.01） and FSH （P<0.05） levels， and lowered the E₂ level （P<0.05）. In addition， Youguiyin up-regulated the protein level of AMPK （P<0.05） and down-regulated the mRNA levels of mTOR and HIF-1 （P<0.01） as well as the mRNA and protein levels of VEGF （P<0.01）. Siwutang down-regulated the mRNA levels of mTOR and HIF-1 as well as the mRNA and protein levels of VEGF （P<0.05）. Zuoguiyin down-regulated the mRNA level of mTOR and the protein and mRNA levels of VEGF （P<0.05）. ConclusionGuishenwan may improve the ovarian function and promote follicle maturation in a rat model of follicular dysplasia by inhibiting the AMPK/mTOR/HIF-1/VEGF pathway， with the therapeutic effect superior to Zuoguiyin， Youguiyin， and Siwutang. It was hypothesized that this model presented the syndrome of kidney-essence deficiency.

Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

ObjectiveTo determine the pathogens and drug resistance in patients with bacterial diarrhea in Lishui City of Zhejiang Province from 2015 to 2019， and provide scientific evidence for prevention and treatment of bacterial diarrhea. MethodFecal specimens were collected from patients with diarrhea in the People’s Hospital of Lishui City from 2015 to 2019. Bacteria were identified by time-of-flight mass spectrometer and serum agglutination reaction. Drug sensitivity in the suspected bacteria was identified by VITEK 2 Compact system. ResultsA total of 2 937 fecal samples were tested from 2015 to 2019， of which 191 were positive for bacteria. The prevalence was 6.65% in male and 6.32% in female. It was highest in the age group 21‒30 years old， followed by the group 51‒60 years old. Summer was the season with the highest prevalence of bacteria. Furthermore，the bacterial species included salmonella （3.98%）， Vibrio parahaemolyticus （1.43%）， aeromonas （0.48%）， shigella （0.37%） and other bacteria （3.66%）. Salmonella had high resistance to cefuroxime and amikacin. Vibrio parahaemolyticus and shigella had high resistance to ampicillin. Aeromonas had high resistance to ampicillin and ampicillin/sulbactam. ConclusionPrevalence of bacteria differs by gender， age and seasons in patients with bacterial diarrhea in Lishui from 2015 to 2019. Salmonella is the principal pathogen in bacterial diarrhea. Additionally， multiple drug resistance is commonly identified. Therefore， it warrants strengthening the pathogenic surveillance on bacteria and drug resistance in bacterial diarrhea.

Objective:To explore the effect of flipped classroom combined with scenario simulation in the teaching reform on four basic medical puncture techniques of clinical skills training.Methods:A total of 1 275 students majoring in five-year clinical medicine in Guangzhou Medical University were enrolled in the study. The control group (647 cases from Batch 2015) were given the traditional teaching pattern and the experimental group (628 cases from Batch 2016) adopted flipped classroom combined with scenario simulation. At the end of the course, the performance in the tests of four basic medical puncture techniques in the objective structured clinical examination (OSCE) of the two groups were compared. The feedback and evaluation of this teaching mode in the experimental group were investigated by questionnaires. SPSS 19.0 was used for independent samples t test. Results:All the scores of the tests of four basic medical puncture techniques in the experimental group were significantly higher than those in the control group: abdominocentesis [(87.89±7.13) vs. (82.60±10.74) points], thoracocentesis [(85.20±7.39) vs. (81.96±7.76) points], bone marrow aspiration [(88.13±6.00) vs. (83.50±9.63) points], and lumbar puncture [(91.91±7.19) vs. (80.74±12.20) points], with significant differences ( P<0.001). The results about the feedback and evaluation in the experimental group showed that the students gave an average score of 8.4 points to their satisfaction with the new teaching mode. The approval rates of the teaching effect evaluation items such as teaching arrangement, improving learning ability, improving clinical practice ability and school promotion were higher than 90.0%. Conclusion:Flipped classroom combined with scenario simulation, which is worthy to be popularized, can not only improve the students' performance in the tests of four basic medical puncture techniques in the OCSE, but also improve teaching satisfaction and teaching effect.

Objective:To evaluate the drug-drug interactions and the tolerability of combined medication between yimitasvir phosphate capsules with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets in healthy volunteers.Methods:A randomized, open, and continuous administration design was used in trial 1 (yimitasvir phosphate capsules with sofosbuvir tablets). 28 subjects were randomly divided into two groups. A non-randomized, open design was used in trial 2 (yimitasvir phosphate capsules with omeprazole magnesium enteric-coated tablets), and included 42 subjects divided into three groups. The open design method was used in trial 3 (yimitasvir phosphate capsules with rosuvastatin calcium tablets), and included 14 subjects. The plasma concentrations of yimitasvir phosphate, sofosbuvir and their main metabolites GS-331007, omeprazole and rosuvastatin were validated by a liquid chromatography/tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by Phoenix winNonlin software.Results:(1) in trial 1, after single and co-administration, the 90% CI of sofosbuvir C max and AUC 0-tau geometric mean ratio (GMR) were 152.0% (118.0% ~ 197.0%) and 230.0% (184.0% ~ 287.0%), with an increase of 52.0% and 130.0% compared to single dose of sofosbuvir, respectively. The 90% CI of GS-331007 C max GMR was 74.0% (67.5% ~ 81.2%) and reduced by 26% compared to single dose of sofosbuvir. (2) in trial 2, the 90% CI of C max GMR after yimitasvir single or co-administration at the same time, with a 4-hours interval, or with a 12- hours interval were 68.9% (44.5% ~ 106.7%) , 64.0% (43.8% ~ 93.6%) and 56.4%(38.9% ~ 81.9%), and the 90% CI of AUC 0-t GMR were 68.6% (46.5% ~ 101.2%), 68.3% (47.6% ~ 98.0%) and 60.5% (41.8% ~ 87.5%), respectively. Compared with single dose of yimitasvir, the C max and AUC 0-t were decreased by 31.1% and 31.4%, 36.0% and 31.7%, 43.6% and 39.5%, respectively. (3) In trial 3, after single and co-administration, the 90% CI of rosuvastatin C max and AUC 0-72 GMR were 172.4% (153.6% ~ 193.5%) and 158.0% (144.3% ~ 172.9%), respectively, with an increase of 74.9% and 60.5% compared to single dose of rosuvastatin. There were no serious adverse events and adverse events leading to withdrawal from the trial. Conclusion:Yimitasvir phosphate capsules have drug-drug interactions with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets.

OBJECTIVE： To investigate the inhibitory effect and potential mechanism of Brucein D （BD） combined with Taxol on the proliferation of human pancreatic cancer Capan-2 cells. METHODS： Using Capan-2 cells as object， the proliferations after treated with BD （5， 10， 15， 20 μmol/L）， Taxol （10， 20， 30， 40 nmol/L） and BD+Taxol （5 μmol/L+10 nmol/L， 10 μmol/L+20 nmol/L， 15 μmol/L+30 nmol/L， 20 μmol/L+40 nmol/L） for 48 h were determined by sulfonyl rhodamine B method. Survival rate of cells and combination index （CI） were calculated. The clone formation assay was performed to detect the formation of clonal colonies after treated with BD （20 μmol/L，hereinafter）， Taxol （40 nmol/L，hereinafter）、BD+Taxol （20 μmol/L+40 nmol/L，hereinafter） for 24 h. The rate of clone formation was calculated. DAPI method was used to observe the apoptosis of cells after treated with BD， Taxol and BD+Taxol for 24 h. Western blotting was used to detect the expression of apoptosis-related protein （Bcl-2， PARP， Caspase-3， Cleaved-caspase-3） after treated by BD， Taxol， BD+Taxol for 48 h and the expression of JNK and p-JNK after treated by BD， Taxol， BD+Taxol for 4， 6， 12 h. RESULTS： After treated with 10， 15 and 20 μmol/L BD， 20， 30 and 40 nmol/L Taxol or two-drug combination for 48 h， survival rates of cells were decreased significantly； the survival rate of drug combination group was significantly lower than the same dose of BD group and Taxol group （P＜0.05）. CI values of drug combination groups （BD 5 μmol/L+Taxol 10 nmol/L， BD 10 μmol/L+Taxol 20 nmol/L， BD 15 μmol/L+Taxol 30 nmol/L， BD 20 μmol/L+Taxol 40 nmol/L） were 0.63±0.04， 0.68±0.08， 0.89±0.12 and 0.84±0.05. After treated with 20 μmol/L BD， 40 nmol/L Taxol and two-drug combination， the formation of clonal colonies was decreased with different degrees of chromatin concentration and nuclear shrinkage； the rate of clone formation （24 h）， the expression of Bcl-2 （48 h）， PARP （48 h）， Caspase-3 （48 h） and JNK （4， 6 h， except for Taxol group） were decreased significantly， while the relative expression of Cleaved-caspase-3 （48 h） and p-JNK （4， 6， 12 h） were increased significantly. Those of BD+Taxol group were significantly better than those of BD group and Taxol group [except for JNK （4， 6， 12 h）， p-JNK （4 h）] （P＜0.05 or P＜0.01）. CONCLUSIONS： Both BD and Taxol can inhibit the proliferation and promote apoptosis of human pancreatic cancer Capan-2 cells， and the combination have a certain synergistic effect， which is better than any single drug. It may be associated with activating Caspase pathway and JNK phosphorylation.

Objective To evaluate the histocompatibility of an original Chinese-made mid-urethral sling (Repelvica mid-urethral sling). Methods In total 10 female New Zealand white rabbits were implanted with Repelvica mid-urethral sling or tension-free vaginal tape-obturator tape (TVT-O;Gynecare). Both brands of sling were implanted under deep fascia of the abdominal wall and in the space between vagina and bladder. All animal groups were sacrificed at set time intervals (4 weeks and 12 weeks), and the abdominal and vaginal slings were harvested for histological evaluation. Results All slings appeared to be well incorporated into the abdominal wall and anterior vaginal wall. All specimens showed a thin, loose, fibrous interface between the synthetic graft and abdominal wall or vaginal wall, along with mild inflammatory reaction from 4 weeks to 12 weeks. Abdominal grafts of Repelvica mid-urethral sling and TVT-O induced comparable tissue reaction (histological score 10.5 versus 10.5 at 4 weeks, 10.0 versus 9.5 at 12 weeks; both P>0.05). Vaginal grafts of Repelvica mid-urethral sling had lower histological score than TVT-O (histological score 6.0 versus 12.0 at 4 weeks, 8.5 versus 12.5 at 12 weeks), however the differences were not statistically significant (both P>0.05). Conclusions Chinese-made Repelvica mid-urethral sling exhibits good histocompatibility. Vaginal graft of Repelvica mid-urethral sling evoks minor tissue reaction,which could be attributed to its lightweighted property and favored its clinical application.

Objective To evaluate the sensitivity and specificity of enzyme assays,and to provide disease spectrum of lysosomal storage diseases (LSDs).Methods Three thousand three hundred and sixty-four high risk individuals were screened for 24 LSDs at Guangzhou Women and Children's Medical Center between January 2009 and December 2016.Twenty-two kinds of enzyme activities from peripheral blood leucocytes or plasma were measured by using the fluorometry or colorimetry of corresponding artificial substrates,screening for 24 LSDs diseases.Measurement data were represented by (x) ± s,and count data were expressed as a percentage or composition ratio.Results A total of 283 subjects were diagnosed with 18 different kinds of LSDs,and the positive rate of high-risk screening was 8.4％.Among the identified patients,172 cases (60.8％) were mucopolysaccharidosis (MPS),79 cases (27.9％) were sphingolipidoses,18 cases (6.4％) were Pompe diseases,10 cases (3.5％) were affected with mucolipidoses,3 cases (1.1％) were glycoprotein storage diseases,and 1 case(0.4％) was Wolman disease.Of the MPS cases,there were 75 cases of MPS Ⅱ (43.6％),45 cases of MP5 ⅣA (26.2％),24 cases of MPS Ⅵ (14.0％) and 20 cases of MPS Ⅰ (11.6％).Gaucher disease (23/79 cases,29.1％) and metachromatic leukodystrophy (MLD) (21/79 cases,26.6％) were common in sphingolipidoses group.Both the sensitivity and specificity of enzyme assays on peripheral blood leucocytes for LSDs were 100％.Conclusions The most common kinds of LSDs are MPS Ⅱ,MPS Ⅳ A,MPS Ⅵ,Gaucher disease,MLD and Pompe disease.Leukocyte enzymology analysis of high-risk screening LSDs has high sensitivity and specificity.