Based on LI Gao's theory of "heavy obstruction" and "blockage of the nine orifices"， this paper proposes the pathological concept of "heavy obstruction and orifice blockage". It is suggested that the core pathogenesis of functional constipation （FC） lies in simultaneous sinking of spleen and lung， together with accumulation and obstruction of dampness and turbidity， resulting in impaired movement of intestinal qi. Within this framework， spleen deficiency with sinking of dampness is considered as the primary pathological mechanism of outlet obstructive constipation （OOC）， while sinking of lung qi is regarded as the key mechanism underlying slow transit constipation （STC）. When both pathological mechanisms coexist， mixed constipation （MC） develops. Guided by this theory， FC is classified into three patterns for syndrome-based treatment. OOC is treated by promoting bowel movement， descending turbid pathogens， and opening the orifices to restore function， with self-formulated Shengxian Tongqiao Decoction （升陷通窍汤）. STC is treated by diffusing lung qi， regulating spleen function， raising sinking qi， and promoting transportation， with self-formulated Xuanfei Yunpi Decoction （宣肺运脾汤）. MC is treated by regulating lung and spleen function， simultaneously raising clear qi and descending turbidity， with self-formulated Xuanyun Tongqiao Decoction （宣运通窍汤）. In clinical practice， modifications should be made according to accompanying syndromes and individual conditions.

Based on LI Gao's theory of "heavy obstruction" and "blockage of the nine orifices"， this paper proposes the pathological concept of "heavy obstruction and orifice blockage". It is suggested that the core pathogenesis of functional constipation （FC） lies in simultaneous sinking of spleen and lung， together with accumulation and obstruction of dampness and turbidity， resulting in impaired movement of intestinal qi. Within this framework， spleen deficiency with sinking of dampness is considered as the primary pathological mechanism of outlet obstructive constipation （OOC）， while sinking of lung qi is regarded as the key mechanism underlying slow transit constipation （STC）. When both pathological mechanisms coexist， mixed constipation （MC） develops. Guided by this theory， FC is classified into three patterns for syndrome-based treatment. OOC is treated by promoting bowel movement， descending turbid pathogens， and opening the orifices to restore function， with self-formulated Shengxian Tongqiao Decoction （升陷通窍汤）. STC is treated by diffusing lung qi， regulating spleen function， raising sinking qi， and promoting transportation， with self-formulated Xuanfei Yunpi Decoction （宣肺运脾汤）. MC is treated by regulating lung and spleen function， simultaneously raising clear qi and descending turbidity， with self-formulated Xuanyun Tongqiao Decoction （宣运通窍汤）. In clinical practice， modifications should be made according to accompanying syndromes and individual conditions.

Acute ischemic stroke is the most common type of stroke, characterized by high mortality, disability, and recurrence rates. Intravenous thrombolysis is the core treatment method. Among them, alteplase is effective as the standard drug, but it has limitations such as narrow time window, high risk of bleeding, and the need for continuous infusion. The new generation of improved drug tenecteplase has the advantages of single intravenous injection and higher fibrin specificity, making it a potential alternative drug to alteplase. In addition, endovascular therapy compensates for the low recanalization rate of large vessel occlusion on the basis of intravenous thrombolysis. This article reviews the clinical progress of teneplase in the treatment of acute ischemic stroke, aiming to provide reference for optimizing the treatment plan of acute ischemic stroke.

Objective To explore the effects and mechanism of Jianpi Shuyi Decoction in improving pancreatic fibrosis in chronic pancreatitis(CP)based on network pharmacology and animal experiments.Methods TCMSP was used to screen the active components and targets of Jianpi Shuyi Decoction.GeneCards was used to obtain the disease targets of pancreatic fibrosis,and the intersection of drug and disease targets was used to construct the protein interaction network and the drug-component-target network,and the core target genes were screened out.GO and KEGG pathway enrichment analysis was performed on the intersecting targets.Caerulein was used to induce CP mouse model,and Jianpi Shuyi Decoction was given for gavage.HE and Sirius red staining were used to observe pancreatic tissue inflammation and collagen deposition,respectively.RT-qPCR was used to observe the mRNA expression levels of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue.Immunohistochemistry staining was used to observe the protein expression levels of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissues.Results A total of 181 active components were screened from Jianpi Shuyi Decoction,corresponding to 284 targets,with 240 targets overlapping between drugs and disease and the core targets were PTGS2,HSP90AA1,etc.193 signaling pathways were obtained from KEGG pathway enrichment analysis,primarily involving lipids and atherosclerosis,chemical carcinogenic-receptor activation,PI3K-Akt signaling pathway and others.The results of animal experiments showed that,compared with the normal group,the model group showed a large number of inflammatory cell infiltration and collagen deposition in pancreatic tissue,the mRNA expression of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue significantly increased(P<0.01),and the protein expression of α-SMA,COL-1,p-PI3K,p-Akt significantly increased(P<0.01);Jianpi Shuyi Decoction significantly reduced the inflammation and collagen deposition in pancreas of mice,reduced the mRNA expression of Acta2,COL1A1,PI3K and Akt1(P<0.05),and attenuated the protein expression of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissue(P<0.05).Conclusion Jianpi Shuyi Decoction may exert a therapeutic effect on CP pancreatic fibrosis by regulating the PI3K/Akt signaling pathway,attenuating inflammation and collagen deposition in the pancreas,and reducing the levels of α-SMA and COL-1.

Objective To explore the effects and mechanisms of Changpu Yujin Tang(CPYJT)on the NOD-like receptor thermal protein domain associated protein 3/cysteinyl aspartate specific proteinase-1/Gasdermin D(NLRP3/Caspase-1/GSDMD)signaling pathway-mediated neuroinflammation in rats with Tourette syndrome(TS).Methods SPF-grade male SD rats were randomly divided into the Control and TS groups.After successful modeling in the TS group,the rats were randomly divided into the Model,Tiapride,and CPYJT groups,and were treated with the corresponding drugs for 4 weeks.After the treatment,the rats' behavior was scored,H & E staining was used to observe pathological changes in the striatum,ELISA was used to measure the content of IL-1β and IL-18,RT-qPCR was used to detect the expression of NLRP3 and ASC mRNA,and Western blot was used to detect the expression of NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins.Results Compared with the Control group,the Model group showed increased scores of stereotyped and motor behaviors(P＜0.01),pathological changes in the striatal tissue,increased content of IL-1β and IL-18(P＜0.01),and upregulated expression of NLRP3,ASC mRNA,and NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins(P＜0.01).Compared with the Model group,the Tiapride group and the CPYJT group showed decreased scores of stereotyped and motor behaviors(P＜0.01),improved pathological damage in the striatal tissue,reduced content of IL-1β and IL-18(P＜0.01),and inhibited expression of NLRP3,ASC mRNA,and NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins(P＜0.01).Conclusion The therapeutic effect of CPYJT on TS is related to the inhibition of the neuroinflammatory response mediated by the NLRP3/Caspase-1/GSDMD signaling pathway.

Objective To explore the effects and mechanisms of Changpu Yujin Tang(CPYJT)on the NOD-like receptor thermal protein domain associated protein 3/cysteinyl aspartate specific proteinase-1/Gasdermin D(NLRP3/Caspase-1/GSDMD)signaling pathway-mediated neuroinflammation in rats with Tourette syndrome(TS).Methods SPF-grade male SD rats were randomly divided into the Control and TS groups.After successful modeling in the TS group,the rats were randomly divided into the Model,Tiapride,and CPYJT groups,and were treated with the corresponding drugs for 4 weeks.After the treatment,the rats' behavior was scored,H & E staining was used to observe pathological changes in the striatum,ELISA was used to measure the content of IL-1β and IL-18,RT-qPCR was used to detect the expression of NLRP3 and ASC mRNA,and Western blot was used to detect the expression of NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins.Results Compared with the Control group,the Model group showed increased scores of stereotyped and motor behaviors(P＜0.01),pathological changes in the striatal tissue,increased content of IL-1β and IL-18(P＜0.01),and upregulated expression of NLRP3,ASC mRNA,and NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins(P＜0.01).Compared with the Model group,the Tiapride group and the CPYJT group showed decreased scores of stereotyped and motor behaviors(P＜0.01),improved pathological damage in the striatal tissue,reduced content of IL-1β and IL-18(P＜0.01),and inhibited expression of NLRP3,ASC mRNA,and NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins(P＜0.01).Conclusion The therapeutic effect of CPYJT on TS is related to the inhibition of the neuroinflammatory response mediated by the NLRP3/Caspase-1/GSDMD signaling pathway.

Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.

This study aims to investigate the anti-inflammatory and anti-apoptotic effects of total flavonoids of hawthorn leaves(TFHL)on lipopolysaccharide(LPS)-induced inflammatory injury in rat intestinal epithelial(IEC-6)cells,as well as the underlying mechanisms.An in vitro inflam-mation model was first established by treating IEC-6 cells with lipopolysaccharide(LPS).IEC-6 cells were then incubated with three concentrations of TFHL for 24 h prior to a further 24 h LPS treatment.RT-qPCR was used to quantify mRNA levels of the inflammatory genes COX-2 and iN-OS,while Western blotting was used to assess protein levels of the apoptotic markers Bax,cleaved Caspase-3,Bcl-2,and the JNK/p-JNK signaling pathway.Finally,cells were pretreated with TFHL and/or the JNK inhibitor SP600125 for 24 h before LPS exposure for 24 h,in order to evaluate the combined effects of TFHL and SP600125 on LPS-induced inflammatory cytokine expression and apoptotic protein levels in IEC-6 cells.The results showed that,compared with the LPS group,the mRNA level of COX-2 and iNOS in the 2.5,5.0,10.0 mg/L TFHL group and the Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and the Bcl-2 protein level was significantly higher(P＜0.01),p-JNK protein level and p-JNK/JNK ratio decreased significantly(P＜0.01);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+LPS group de-creased significantly(P＜0.01),Bax,and Caspase-3 protein levels decreased significantly(P＜0.01),and the level of Bcl-2 protein increased significantly(P＜0.05);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+SP600125 group decreased significantly(P＜0.01),Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and Bcl-2 protein level increased significantly(P＜0.01).These findings indicate that TFHL exerts anti-inflammato-ry and anti-apoptotic effects in LPS-challenged IEC-6 cells by inhibiting the JNK signaling path-way.

Objective To introduce a case of elevated blood pressure with chills caused by Urinary Kallidinogenase.Methods The diagnosis and treatment of a patient with hypertension and chills induced by uracillin were analyzed retrospectively,and the correlation of adverse drug reactions(ADR)was analyzed The Chinese and English databases of CNKI,Vip,PubMed and Web of Science were searched to analyze the ADR case reports related to yurekline.Results The patient experienced a sudden increase in blood pressure with chills and sweats during the use of uracillin,and the adverse reaction was relieved gradually after withdrawal.According to Naranjo's ADR assessment scale and our manual of ADR reporting and monitoring,the association between uracillin and increased blood pressure with chills was"Probably".Conclusions The increase of blood pressure is a rare side effect of uracillin,so it is necessary to monitor the patients'blood pressure actively during the course of medication.Once the patients have the symptoms of blood pressure fluctuation,body shivering and mental abnormality,the clinic should judge and stop the medication in time to ensure the safety of the patients'medication.

Objective:To evaluate the potential causal relationship between tinnitus and the risk of Alzheimer's disease(AD)onset using the two-sample Mendelian randomization(MR)method and to clarify its mechanism of action,so as to provide new ideas for early warning of AD.Methods:Genome-wide association study(GWAS)database was used to search the keywords"tinnitus"and"Alzheimer"to obtain the related datasets of exposure factor tinnitus and outcome AD;the tinnitus datasets included ukb-d-4803_11,ukb-d-4803_12,ukb-d-4803_13,ukb-b-14254 and ukb-a-384;the AD datasets included ieu-b-5067,ieu-b-2,ieu-a-297,ebi-a-GCST90027158 and ebi-a-GCST002245.The single nucleotide polymorphisms(SNPs)closely and independently associated with tinnitus were screened as instrumental variables(IVs),and the SNPs associated with AD were used as outcomes.Inverse variance weighted(IVW)method was used to conduct MR analysis to evaluate its odds ratio(OR)value,95%confidence interval(CI)and P value;P<0.05 indicated significant causal relationship.Sensitivity detection used Cochran's Q test to detect the heterogeneity of IVs to evaluate its Q value,df value and P value;when IVW method P>0.05,it indicated no significant heterogeneity;MR-Egger intercept was used to detect horizontal pleiotropy;when the intercept was 0 or close to 0 and P>0.05,it indicated no significant horizontal pleiotropy;meanwhile,leave-one-out method was used for sensitivity analysis.Finally,visualization results were performed using forest plot,scatter plot,funnel plot and leave-one-out plot.Results:A total of 286 SNPs were screened as IVs.All instrumental variables satisfied F>10,suggesting no weak instrumental variable;after screening by PhenoScanner web tool,all SNPs were unrelated to confounding factors.When the tinnitus and AD datasets were ukb-d-4803 and ebi-a-GCST90027158 respectively,there was a significant positive correlation between tinnitus and the risk of AD onset(IVW:OR=1.842,95%CI:1.065-3.188,P=0.029);Cochran's Q test suggested no significant heterogeneity of IVs(Q=9.788,df=10.000,P=0.459);MR-Egger intercept indicated no horizontal pleiotropy(Egger intercept=-0.006,P=0.147);leave-one-out method showed stable results,and no SNP with significant influence on the results was detected.Conclusion:There is a positive causal relationship between tinnitus and the risk of AD onset.Neuroinflammation accompanied by persistent microglial activation to varying degrees may be the common pathogenesis of tinnitus and AD;in addition,depression may also act as an upstream factor to hyperactivate the hypothalamic-pituitary-adrenal(HPA)axis,leading to the progression of relationship between tinnitus and AD.