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.

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 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.

A 70-year-old male patient with T2N2M0 stage Ⅲ A lung squamous cell carcinoma was switched to monotherapy with tislelizumab (200 mg by intravenous infusion on day 1, 21 days as a cycle) after 5 cycles of chemotherapy with paclitaxel protein-bound and cisplatin, one cycle of combined chemotherapy and immunotherapy with tislelizumab, paclitaxel protein-bound and cisplatin. After 10 days of tislelizumab administration in the 4th cycle of monotherapy, the patient developed symptoms such as nausea, vomiting, abdominal pain, and abdominal distension. Laboratory tests showed fasting blood glucose of 26.3 mmol/L, glycated hemoglobin of 12.5%, fasting C-peptide<0.01 μg/L, free triiodothyronine of 3.31 pmol/L, free thyroxine of 4.9 pmol/L, and thyroid stimulating hormone of 49.4 mU/L, urinary ketones (++), and urinary glucose (++). Ketoacidosis and hypothyroidism were diagnosed, which was considered to be caused by tislelizumab. After 7 days of treatments with insulin, fluid replacement, potassium supplementation, and maintenance of electrolytes and acid-base balance, the patient′s fasting blood glucose was 7.6 mmol/L. The hypoglycemic regimen was changed to subcutaneous injection insulin glargine (10 U in the morning) and insulin lispro (6 U before breakfast, 5 U before lunch and dinner), and levothyroxine sodium 100 μg once daily orally was given at the same time. Two weeks later, due to the condition, the patient received tislelizumab again once, and subsequently developed ketoacidosis 3 times. Tislelizumab was not used again thereafter. Follow-up once a month within 6 months showed no significant changes in the patient′s thyroid function compared to before. The patient continued to use insulin to control blood glucose.

Objective To investigate the neuroprotective effect of tianma hookteng drink on mice epilepsy(EP)model by inhibiting p38 mitogen-activated protein kinase(p38 MAPK)/nuclear transcription factor-κB(NF-κB)signaling pathway.Methods Forty male Kunming mice were randomly divided into four groups:control group,model group,high-dose tianma hooker drink group and low-dose of tianma hooker drink group according to random number table method,with 10mice in each group.One week before model-ing,the mice in each group was given the appropriate drugs by gavage.Acute EP model in mice was constructed by pilocarpine hydrochlo-ride.The behavioral performance and electroencephalogram(EEG)in mice were evaluated;terminal deoxynucleotidyl transferase-medi-ated dUTP nick end labeling(TUNEL)staining method was applied to detect the number of apoptotic cells in hippocampal tissue of mice in each group;enzyme-linked immunosorbent assay(ELISA)was used to detect the superoxide dismutase(SOD)and malondialdehyde(MDA)levels in serum and tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels in hippocampal tissues;Western blot method was used to detect the protein expression levels of p38 MAPK and phosphorylated nuclear factor kappa B(p-NF-κB)in hippocampal tissue.Results Compared with the control group,continuous epileptiform waves were seen in the EEG of mice in the model group,with a significant increase in the number of spikes,spindles,and spindles-slow waves,and an increase in EP seizure frequency,duration,and seizure level(P＜0.01);neuronal apoptosis rate in hippocampal tissues was significantly elevated(P＜0.01);the lev-el of SOD in serum was decreased,and the level of MDA was increased(P＜0.05);the expression levels of TNF-α,IL-6 and the protein expression levels of p38 MAPK and p-NF-κB p65 were elevated in hippocampal tissue(P＜0.05).Compared with the model group,the frequency and intensity of epileptic waves in the EEG of mice in the high-dose and low-dose groups of tianma hooker drink were significantly reduced,and the frequency,duration and seizure level of EP seizures were reduced(P＜0.05);the apoptotic rate of neurons in hippocampal tissues were all reduced(P＜0.05);the level of SOD was increased,the level of MDA was decreased(P＜0.05);the expression levels of TNF-α,IL-6 and the protein expression levels of p38 MAPK and p-NF-κB p65 were decreased in hippocampal tissues(P＜0.05).Conclusion Tianma hookteng drink may exert anti-EP effect by inhibiting p38 MAPK/NF-κB sig-naling 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.

A 66-year-old man was admitted with acute left heart failure and hyponatremia.On the first day of admission,15 mg tolvaptan tablets were given orally.On the second day of admission,alanine transaminase and aspartate transaminase were significantly increased to 916.76 U·L-1 and 1 857.1 U·L-1,respectively,which met the diagnostic criteria of severe acute liver injury.The drug was immediately stopped and hepatoprotective therapy was given,and on the 10th day of admission,the patient's liver function improved significantly,and on the 12th day of admission,the patient was discharged after his condition stabilised.The results of the correlation evaluation indicated that the development of acute liver injury in this patient is likely related to tolvaptan.This article discusses the mechanism,time of occurrence,population and treatment of tolvaptan-induced liver function injury,suggesting that clinical use of tolvaptan should be highly vigilant for acute liver function injury and routine monitoring of patients' liver function to ensure the safe use of the drug.

A 66-year-old man was admitted with acute left heart failure and hyponatremia.On the first day of admission,15 mg tolvaptan tablets were given orally.On the second day of admission,alanine transaminase and aspartate transaminase were significantly increased to 916.76 U·L-1 and 1 857.1 U·L-1,respectively,which met the diagnostic criteria of severe acute liver injury.The drug was immediately stopped and hepatoprotective therapy was given,and on the 10th day of admission,the patient's liver function improved significantly,and on the 12th day of admission,the patient was discharged after his condition stabilised.The results of the correlation evaluation indicated that the development of acute liver injury in this patient is likely related to tolvaptan.This article discusses the mechanism,time of occurrence,population and treatment of tolvaptan-induced liver function injury,suggesting that clinical use of tolvaptan should be highly vigilant for acute liver function injury and routine monitoring of patients' liver function to ensure the safe use of the drug.

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.