Objective To establish the functional constipated mouse model by compound diphenoxylate, and explore the anti-constipation effect of black garlic polysaccharide. Methods Mouse small intestine ink propulsion experiment and mouse defecation experiment were carried out respectively. The mice in each experiment were randomly divided into blank group, model group, positive group and black garlic polysaccharide （0.25, 0.5, 1 g/kg） groups. Mice in blank group and model group were given distilled water, and in positive group were given lactulose oral solution. Compound diphenoxylate （5 mg/kg） was intragastric administrated after 1 week of administration, and small intestine propulsion experiment and defecation experiment were conducted respectively. Results Compared with model group, intestinal propulsion rate of black garlic polysaccharide groups was significantly increased and first dejection time was significantly shorten, and the number, weight and fecal water content increased significantly at 6 h in middle and high dose groups. Conclusion Black garlic polysaccharide could promote intestinal propelling, shorten defecation time and increase fecal water content.

Objective Fragrant sachets are items with significant Chinese cultural characteristics and have multiple application values, with their medicinal value being an important aspect. Especially in recent years, with the successive outbreaks of SARS, MERS, COVID-19, the medicinal effect of traditional Chinese medicine sachets has been increasingly valued and widely used.However, there are no relevant standards for traditional Chinese medicine sachets at the national, industry, local, or organizational levels, which is not conducive to the healthy development of the industry. To establish standards for traditional Chinese medicine sachets to lead the development of the industry. Methods Based on the review of the current application status of traditional Chinese medicine sachets, a study on the quality standards of traditional Chinese medicine sachets was conducted through investigation and research, data collection, drafting of standard drafts, soliciting opinions, review and approval, and standard verification. Results The first group standard of traditional Chinese medicine sachet in China: Technological specification of traditional Chinese medicine sachet (powder core), which ensures the scientificity, progressiveness, rationality and practicability of the production of the standard of traditional Chinese medicine sachet. Conclusion The established group standard for traditional Chinese medicine sachets are practical, safe, reliable, and easy to implement, providing technical references for the inheritance and promotion of traditional Chinese medicine sachets.

Objective To investigate th effect of PCSK9 inhibitors on early intensive lipid-lowering therapy in patients with symptomatic intracranial atherosclerotic stenosis(ICAS).Method One hundred and thirty-nine symptomatic ICAS patients who attended the Xuzhou Central Hospital from October 2022 to August 2023 were collected.According to the choice of lipid-lowering regimen,they were divided into statin drug group(n=54),PCSK9 inhibitor group(n=42)and combination drug group(n=43).Baseline data,laboratory indices,adverse drug reactions,clinical neurological function scores and endpoint events of the three groups were collected and analyzed.Results There was no statistically significant difference in the clinical data among the three groups before treatment.Compared with pre-treatment,total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)levels were significantly lower in the three groups after treatment(all P＜0.01),and peripheral blood leukocyte counts were significantly lower in the PCSK9 inhibitor group after treatment(P＜0.05).After treatment,the differences in TC and LDL-C levels and the proportions of LDL-C＜1.8 mmol/L after 2 weeks of medication and LDL-C＜1.4 mmol/L on the 90th day were statistically significant among the three groups(all P＜0.01).Compared with the statin drug group,the differences in TC and LDL-C levels and the proportions of LDL-C＜1.8 mmol/L after 2 weeks and LDL-C＜1.4 mmol/L on the 90th day in the PCSK9 inhibitor group and the combination drug group were statistically significant(all P＜0.05).The differences in the occurrence of endpoint events,the proportion of recurrent AIS or TIA,cardiovascular events,and the time to endpoint events among the three groups were statistically significant on the 180th day after treatment(all P＜0.05).Differences in the occurrence of endpoint events,proportion of cardiovascular sexual events,and time to endpoint events on day 180 after treatment were statistically different in the PCSK9 inhibitor group and the combination drug group compared with the statin drug group(all P＜0.05).There was a statistically significant difference among the survival analysis curves of the three groups,with higher event-free survival in both groups with PCSK9 inhibitors alone or in combination(Log-Rank=13.95,P=0.0009).Conclusion Early intensive lipid lowering with PCSK9 inhibitors is effective and safe in patients with symptomatic ICAS,and can further reduce LDL-C,TC,and white blood cell counts,as well as improve lipid compliance,and significantly reduce the rate of end-point events with a significantly prolonged time to occurrence.

Objective:To investigate the efficacy and safety of tocilizumab in the treatment of critically ill children with acute necrotizing encephalopathy (ANE).Methods:It is a retrospective cohort study. The children with ANE admitted to the pediatric intensive care unit of 4 Chinese tertiary hospitals from December 2022 to November 2023 were divided into conventional treatment group and tocilizumab group, and the comparison between groups was performed by using Mann ‐ Whitney U test or Chi-square test. Results:Among 21 cases of severe ANE, there were 11 males with the onset age of 65 (27, 113) months. The duration from onset to PICU admission was 2 (1, 2) days. There were 13 cases of ultra-high fever (greater than 40 ℃), including 18 cases of convulsions, and 19 cases with a GCS score of less than 8 points. The causative agent was novel coronavirus Omicron in 7 cases and influenza A in 14 cases. All cases had central respiratory failure requiring mechanical ventilation. Of the 21 cases, 18 were shock, 15 were coagulopathy, 10 were kidney injury and 13 were liver dysfunction. Of these hospitalized patients, 8 children with ANE were treated with tocilizumab. Eight cases received continuous blood purification (CBP) treatment, 5 of them were combined with plasmapheresis. Serum cytokine levels were elevated in 21 children with ANE, including (interleukin, IL)-6 and IL-8 (61 (22, 1 513) and 68 (5, 296) ng/L). There were 14 cases (67%) deaths, including 11 cases in the conventional treatment group and 3 cases in the tocilizumab group. There was no significant difference in the mortality rate between the two groups ( P=0.056). Tocilizumab-related rash or other adverse events were not observed. Conclusions:The motality of critically ill ANE patients was high. The combination of Tocilizumab with conventional treatment did not reduce the motality of severe ANE patients, and no adverse reactions of tocilizumab were observed.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.

Objective To investigate the impact of the interaction of fasting blood glucose(FBG)and serum uric acid(SUA)on diabetic retinopathy(DR).Methods A total of 306 diabetes mellitus(DM)patients diagnosed and re-ceived comprehensive ophthalmic examination in the First Affiliated Hospital of Gannan Medical University from January 2019 to January 2021 were selected.According to the presence or absence of DR,these patients were divided into the DR group(178 patients)and the non-DR(NDR)group(128 patients).The general clinical data of patients in the two groups were compared.The least absolute shrinkage and selection operator(LASSO)regression method and multivariate Logistic regression analysis were used to screen the independent influencing factors of DR in DM patients,and the odds ratio of risk factors was calculated.The sensitivity analysis of the results was performed using the E-value method.The interaction of FBG and SUA on DR in DM patients was analyzed by an additive interaction model.The Nomogram model to predict DR in DM patients was constructed and verified internally.The receiver operating characteristic curve(ROC)was used to evalu-ate the effects of FBG,SUA and both FBG and SUA on DR in DM patients.Results Compared with the NDR group,the course of DM in the DR group was significantly longer,the proportion of patients with history of oral medication was signif-icantly lower,the proportion of patients with history of insulin therapy was significantly higher,and the levels of total cho-lesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,blood urea nitrogen,serum creatinine,SUA and FBG were significantly higher(all P＜0.05).The history of insulin therapy,course of DM≥9.66 years,TG≥2.07 mmol·L-1,SUA ≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 were the risk factors for DR in DM pa-tients,while the history of oral medication was the protective factor for DR in DM patients.The Nomogram model based on the above independent risk factors was accurate in predicting the occurrence of DR in DM patients.SUA and FBG had inter-active effects on DR in DM patients.The value of SUA-FBG interaction in the diagnosis of DR was greater than that of both alone.Conclusion SUA≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 are the risk factors for DR in DM patients.The value of interaction of FBG and SUA in the diagnosis of DM accompanied by DR is greater than that of both alone.

Diabetes mellitus is a complex metabolic disease involving multiple organ systems in the body.In recent years,its global incidence rate has increased year by year.In China,the blood glucose control of patients with diabetes mellitus who receive oral hypogly-cemic agents or insulin treatment remains poor.In the early disease stages,exercise is important to control blood glucose levels.Recently,many studies have found that the occurrence of type 2 diabetes mellitus was related to declining levels of irisin,an exercise-related muscle factor.Furthermore,studies have found that irisin improved insulin resistance,promoted the production of pancreatic isletβcells,and affected the body's glucose and lipid metabolism.In addition,its levels were also implicated in the occurrence of various complications,such as diabetic nephropathy and diabetes-related cardiovascular diseases.This article summarizes and analyzes the role of irisin in the occurrence and development of diabetes mellitus and further describes its impact and mechanism on various diabetic complications.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.

Objective To screen the pharmacodynamic material basic components of Artemisiae Annuae Herba and study its antioxidant activity in vitro by investigating the spectrum-effect relationship between the HPLC fingerprints of 11 batches of Artemisiae Annuae Herba(dried aerial part of Artemisia annua L.).Methods The determination was performed on Aglient C18 column(250 mm×4.6 mm,5 μm)with mobile phase consisted of 0.2%phosphoric acid solution-Methanol(gradient elution)at the flow rate of 1.0 ml/min.The column temperature was indoor temperature,and detection wavelength was 220 nm,with sample size of 10 μl.Using isochlorogenic acid A as reference,HPLC fingerprints of 11 batches of samples were determined.The common peaks of 11 batches of samples were identified and recorded through TCM chromatographic fingerprint similarity evaluation system(2012 edition).Using scavenging rate of DPPH and ABTS free radical as pharmacodynamic indicators of antioxidant effects,SIMCA 14.1 analysis software was used for PLSR to establish the spectra-effect relationship.Results There were 48 common peaks on 11 batches of sample,11 components were identified as scopoletin,scoparone,isochlorogenic acid B,A,C,luteolin,apigenin,chrysosplenetin,artemisinin,artemisetin and artemisinic acid.The scavenging activity of 11 batches of samples to DPPH and ABTS free radicals was detected.The spectrum-effect relationship showed that isochlorogenic acid A,B,C and scoparone were positively associated with its antioxidant capacity,and variable projection value was greater than 1.It was suggested that these components were the material basis of antioxidant effect in Artemisiae Annuae Herba.Conclusion This study investigates the antioxidant capacity of different substances in Artemisiae Annuae Herba in vitro,and proves that isochlorogenic acid A,B,C and scoparone play a major role for the antioxidant capacity.

Objective To explore the effect of Bajitianwan(BJTW)formula on bone formation of Aβ-injured osteoblasts and its mechanism.Methods Osteoblasts isolated from neonatal 24-hour Wistar rats were used for the study,and osteoblasts were subjected to damage with Aβ1-42 oligomers,and pharmacological intervention was performed with the aqueous extract of BJTW formula.The MTT assay,alkaline phosphatase(ALP)activity assay,catalase(CAT)activity assay,superoxide dismutase(SOD)activity assay,glutathione(GSH)activity assay and malondialdehyde(MDA)activity assay were carried out respectively.The expression levels of bone morphogenetic protein 2(BMP2),osteogenic specific transcription factor(RUNX-2)and osteoprotective protein(OPG)were detected by Western blotting.After confirming the effect of BJTW formula on Aβ-injured osteoblasts,the network pharmacology method was used to predict the potential pathways.Results The BJTW formula significantly promoted the proliferation of Aβ-injured osteoblasts,increased ALP,SOD and GSH activity,inhibited MDA activity,and promoted the expression of bone formation-related proteins BMP2,RUNX-2 and OPG.Network pharmacological analysis showed that the effect of ameliorating of Aβ-injured osteoblasts by BJTW formula was mainly mediated by AGE-RAGE,PI3K-Akt,MAPK and neuroactive ligand-receptor interaction signaling pathways.Conclusion In this study,the effect of BJTW formula on improving the osteoblasts damaged by Aβ was confirmed for the first time,and its related mechanism was explored based on network pharmacology method.The results lay a strong foundation for the clinical application of traditional formula BJTW against osteoporosis.