AIM:To investigate the effects of Panax notoginseng compound formula(PN)on endometrial fibro-sis by regulating inflammatory reaction and intestinal flora(IF)in a rat model of intrauterine adhesion(IUA).METHODS:The rat IUA model was established by following the mechanical injury method.A total of 50 rats were randomly divided in-to sham group,model group,low-dose(210 mg/kg)PN group,medium-dose(420 mg/kg)PN group and high-dose(840 mg/kg)PN group.After 8 weeks of intragastric administration,the uterus was collected to observe morphological changes with naked eye.The degree of uterine tissue damage and fibrosis was evaluated through hematoxylin-eosin(HE)and Mas-son staining.The collagen type Ⅰ(Col Ⅰ)was detected by immunohistochemistry.The interleukin-6(IL-6)and IL-10 pro-tein expression was detected by Western blot.The levels of IL-6,IL-1β,tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor B(VEGFB)were detected by enzyme-linked immunosorbent assay(ELISA).The IF diversity and population structure were observed by 16S amplicon.RESULTS:Compared with the sham group,the uteruses of rats in the model group showed:reduced elasticity,accompanied by congestion and edema;decreased number of glands and blood vessels,and thinned endometrium(P<0.01);increased collagen fibers and Col Ⅰ protein expression(P<0.01);sig-nificantly increased IL-1β,IL-6,TNF-α and VEGFB levels in the uterine tissue(P<0.01);decreased IL-10 level(P<0.01);and reduced IF diversity(P<0.05).Compared with the model group,the drug intervention groups exhibited:re-covered elasticity of the uterus and relieved congestion and edema;increased number of endometrial glands and blood ves-sels(P<0.05);decreased collagen fibers and Col Ⅰ protein expression(P<0.01);reduced IL-1β,IL-6,and TNF-α lev-els to varying degrees in the uterine tissue(P<0.05);elevated IL-10 level(P<0.01);and improved IF diversity(P<0.05).CONCLUSION:The PN is able to significantly improve the endometrial tissue fibrosis in IUA rats.The under-lying mechanisms may be related to the inhibition of IL-6,IL-1β and TNF-α expression,up-regulation of IL-10,and im-provement of IF diversity.

Objective To establish an analytical method combining gas chromatography-tandem mass spectrometry(GC-MS)and liquid chromatography-tandem mass spectrometry(LC-MS)to detect diazepam residue in bait nest materials and fish samples,and improve the pretreatment steps of samples to make the experimental results accurate and the sample processing convenient and fast.Methods Taking diazepam as the research object,samples were extracted with methanol and dichloromethane/n-hexane as solvents according to the type,and the supernatant was taken for detection after centrifugation.Results The diazepam standard sample showed a good linear relationship in the range of 10～10 000 ng/mL.The retention times in methanol and mixed solvent were 13.54 min and 13.83 min,respectively,and the correlation coefficients were 0.998 and 0.999,respectively;The limit of detection(LOD)of using methanol as extraction solvent was 2 ppb,and limit of quantification(LOQ)was 6 ppb.The LOD of using mixed solvents was 5 ppb,and the LOQ was 15 ppb.When the sample is a bait nest material,the GC-MS spectrum was clear and standard,and the peak shape was sharp and prominent;When the sample is biological specimen,the GC-MS spectra are disturbed by matrix,while the LC-MS data is more accurate and faster.Conclusion It is more appropriate to use GC-MS to determine the content of bait nest materialsamples,and it is more accurate to LC-MS to determine the content of fish samples due to the complexity of the organism.

Objective To explore the factors influencing enteral nutrition intolerance in critically ill patients and to develop a risk prediction model to provide medical staff with a tool for early identification of patient intolerance.Methods Domestic and international databases such as CNKI,PubMed and Web of Science were searched and supplemented by searching references and grey literature.The search period was from inception to November 2022.Data were independently screened and extracted by 2 systematically trained researchers,and the quality of the literature was evaluated.Meta-analysis was performed using Review Manager 5.4 software.The OR value of the comprehensive effect of the factors was taken as the coefficient of each factor in the formula,and the natural logarithm of the ratio of intolerance incidence and non-incidence was the constant term of the formula.From December 2022 to June 2023,360 patients who met the inclusion and exclusion criteria in the ICU of a tertiary hospital were collected as a model verification group by convenient sampling method,and the collected clinical data were substituted into the formula to evaluate the discrimination and calibration of the model.Results A total of 13 articles were included.7 influencing factors with more than 3 times of reports and statistically significant results were obtained.For age[OR=0.97,95％CI(0.94,0.99),P=0.010],Acute Physiology and Chronic Health Evaluation scoreⅡ[OR=1.17,95％CI(1.01,1.36),P=0.040],comorbidity with diabetes[OR=1.21,95％CI(1.05,1.40),P=0.008],comor-bidity with neurological diseases[OR=0.85,95％CI(0.74,0.98),P=0.020],mechanical ventilation[OR=3.21,95％CI(1.82,5.66),P＜0.001],using sedative analgesics[OR=2.27,95％CI(1.66,3.10),P＜0.001],using gastric motility drugs[OR=0.23,95％CI(0.15,0.36),P＜0.001].The incidence of enteral nutrition intolerance was 35.00％.The risk prediction model for enteral nutrition intolerance in critically ill patients was logit(P)=-0.619-0.031×age+0.157 × APACHE Ⅱ+0.191 ×comorbidity with diabetes-0.163 ×comorbidity with neurosurgery+0.820 ×using sedatives and analgesics+1.166×mechanical ventilation-1.470×using gastric dynamic drugs.The area under the receiver operating characteristic curve of the model was 0.864.The maximum Youden index was 0.589.The sensitivity was 0.922.The specificity was 0.667.The corresponding clinical diagnostic threshold was 0.536.Hosmer-Leme-show test x2=13.410,P=0.098.Brier score was 0.195.Conclusion The risk prediction model of enteral nutrition intolerance in critically ill patients based on large sample evidence-based medicine is universal,scientific and practical.It provides a tool for medical staff to identify patients with enteral nutrition feeding intolerance in ICU.

Objective:To construct a perioperative activity program for patients with minimally invasive esophageal cancer under enhanced recovery after surgery (ERAS) concept through literature review and Delphi method.Methods:This was a single-center and interview study. Databases and websites including PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Medive and other databases and websites were searched systematically for articles related to esophageal cancer and upper digestive tract cancer patients′ activities from January 1, 2002 to January 31, 2022. In this single-center and interview study, literature review and group discussion were conducted to form a preliminary activity program, and then Delphi method was used to further demonstrate the practicability and feasibility of the activity program.Results:The overall program and specific intervention methods of perioperative activity program for minimally invasive esophageal cancer patients under ERAS concept were constructed, including 3 first-level indicators, 9 second-level indicators and 35 third-level indicators.Conclusions:Perioperative activity program of patients with minimally invasive esophageal cancer is scientific and reasonable, which can provide reference for medical staff and patients.

OBJECTIVE To explore the improvement effect and potential mechanism of Baicao fuyanqing suppository on bacterial vaginitis （BV） in rats. METHODS The female SD rats were randomly divided into normal group， model group， metronidazole group （positive control， 0.03 g/kg）， Baicao fuyanqing suppository low-dose， medium-dose and high-dose groups （0.18， 0.36， 0.72 g/kg）， with 8 rats in each group. Except for the normal group， the rats in other groups were injected subcutaneously with 0.2 g of Estradiol benzoate injection+20 μL of Escherichia coli suspension （2×108～3×108 cfu/mL） through the vaginal opening to establish the BV rat model. Administration groups were given relevant medicine vaginally， while the normal group and the model group were given normal saline， once a day， for 6 consecutive days. Twenty-four hours after the last administration， the vaginal appearance score and vaginal pH were measured for each group of rats. The levels of cytokines [interleukin-1β （IL-1β）， IL-2， IL-13， immunoglobulin A （IgA）] in vaginal lavage fluid were determined. The morphology of the uterus and accessories， and pathological changes in the vaginal tissue were observed. The expressions of Toll-like receptor 2 （TLR2）， TLR4 and nuclear factor-κB （NF-κB） in vaginal tissues were determined. RESULTS Compared with the normal group， the uterus edema， the irregular shape of uterus and accessories， the vaginal mucosa hyperplasia， and the massive desquamation of epithelial cells were observed in the model group， complicating with massive infiltration of inflammatory cells； vaginal opening redness and swelling score and secretion score， vaginal pH， the levels of proinflammatory cytokine IL-1β and IL-2， the protein expressions of TLR2， TLR4 and NF- κB were all increased or up-regulated， while the levels of IgA and anti-inflammatory cytokine IL-13 decreased significantly （P＜0.05 or P＜0.01）. Compared with the model group， varying cn degrees of improvement in uterine and accessories， and vaginal tissue lesions in rats were observed in administration groups， and most of the quantitative indicators mentioned above showed significant improvement （P＜0.05 or P＜0.01）. CONCLUSIONS Baicao fuyanqing suppository has a certain improvement effect on inflammatory symptoms in BV rats， and its mechanism may be related to the inhibition of the TLR/NF-κB signaling pathway.

Objective:To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYFⅢ) in regulating mucus hypersecretion of chronic obstructive pulmonary disease (COPD).Methods:According to the efficacy of the original Chinese medicine, the components of ECC-BYFⅢ were divided into four categories: Buqi (Ginsenoside Rh1+Astragaloside), Bushen (Icariin), Huatan (Nobiletin), and Huoxue (Paeonol). The four categories were divided into 14 groups based on the method of mathematical permutation. ① The rats were divided into control group, model group, ECC-BYFⅢ, and different components compatibility groups according to the random number table, totaling 17 groups. COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The corresponding drugs were given by gavage at the 9th week of modeling, and the samples were collected at the end of the 16th week. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase 1 (TIMP-1) in serum and bronchoalveolar lavage fluid (BALF), and the levels of mucin (MUC) 5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay (ELISA). ② Human lung epithelial cells BEAS-2B were divided into blank group, model group, and different components compatibility groups. Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment. The mRNA expressions of MUC5AC, MUC5B, and MUC1 were detected by quantitative polymerase chain reaction (PCR). The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region (R) value comprehensive evaluation method.Results:① Compared with the control group, MMP-9 in serum and BALF from the model group were significantly increased, the level of TIMP-1 was significantly decreased, and MUC5AC in lung tissue and BALF were significantly increased. The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups, ECC-BYFⅢ and other components compatibility groups significantly corrected mucus hypersecretion in COPD rats, ECC-BYFⅢ, Bushen Quxie, Fuzheng Huatan, and Quxie groups were much better (R values were 2.15±0.42, 2.11±0.23, 2.16±0.23 and 2.16±0.55, respectively), compared with the model group (R value: 3.00±0.00), the differences were statistically significant (all P < 0.05). ② Compared with the blank group, the mRNA expressions of MUC5AC, MUC5B, and MUC1 increased in the model group. But different components compatibility groups had no significant effects on the mucus secretion of BEAS-2B cells. ③ The comprehensive evaluation results of R value about each in vivo and in vitro index showed that ECC-BYFⅢ, Huoxue, Quxie, Bushen Huoxue, Fuzheng Huatan, Buqi Quxie groups significantly corrected the mucus hypersecretion (R values were 2.30±0.43, 2.33±0.44, 2.12±0.68, 2.27±0.64, 2.24±0.27 and 2.29±0.47, respectively), compared with the model group (R value: 3.00±0.00), the difference was statistically significant (all P < 0.01). The order was: Quxie > Fuzheng Huatan > Bushen Huoxue > Buqi Quxie > ECC-BYFⅢ > Huoxue. Conclusions:Different components compatibility of ECC-BYFⅢ had different effects on COPD mucus secretion. The components containing Huatan (Nobiletin) or Huoxue (Paeonol) showed a better inhibitory effect on mucus secretion.

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

Objective To investigate the clinical value of aspirin before pregnancy combined with low molecular heparin during pregnancy on treatment of patients with recurrent spontaneous abortion caused by prethrombotic state.Methods A total 60 patients with recurrent spontaneous abortion were randomly divided into treatment group and control group,30 cases in each group.The treatment group was treated with small dose of aspirin before pregnancy and low dosage molecular heparin during pregnancy,while the control group was treated with low dosage molecular heparin during pregnancy.Pregnancy outcome was compared between two groups.Results The partus maturus rate of treatment group was significantly higher than control group (P ＜ 0.05),and abortion rate was significantly lower than control group (P ＜ 0.05).Conclusion Aspirin before pregnancy combined with low molecular heparin during pregnancy is effective in treatment of patients with recurrent spontaneous abortion caused by prethrombotic state,which can increase partus maturus rate and reduce abortion rate.

Objective To explore clinical effect of compound danshen dropping pills,aspirin enteric-coated tablets combined with small dose of estrogen on treatment of patients with thin endometrium.Methods A total of 69 patients with thin endometrium were collected and divided into 3 groups.Group Ⅰ was treated with estrogen at 3 to 5 days after menstrual period,group Ⅱ was treated with aspirin and compound danshen dropping pills,and group Ⅲ was treated with estrogen,aspirin and compound danshen dropping pills.General condition,ovulation,drug use,endometrial growth before and after the use of drugs and pregnancy rate were compared.Results There were no significant differences in general situations and ovulation results before treatment among three groups (P ＞0.05).After medication,the endometrial thickness of the 3 groups improved significantly,and the endometrial thickness of group Ⅲ was significantly better than group Ⅰ and Ⅱ (P =0.005,0.012).In group Ⅰ,Ⅱ and Ⅲ,the proportion of endometrium more than 7 mm after treatment was 38.1％,16.7％ and 60％ respectively,and the success rate of group Ⅲwas significantly higher than that of group Ⅰ and Ⅱ (P =0.008).The clinical pregnancy rate in group Ⅲ was significantly higher than that in group Ⅰ and Ⅱ (P =0.049).Conclusion Compound danshen dropping pills,aspirin entericcoated metformin combined with small dose of estrogen can significantly improve endometrium and pregnancy rate in patients with thin endometrium,with less estrogen dosage.