This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

OBJECTIVE To investigate the mechanism of cordycepin in delaying the transformation from acute kidney injury （AKI） to chronic kidney disease （CKD） （short for “AKI-CKD”）. METHODS Network pharmacology and bioinformatics were used to analyze and predict the signaling pathways of cordycepin in delaying AKI-CKD progression and its relationship with the ferroptosis pathway. Cell experiments were performed to verify the predicted results. Human renal tubular epithelial HK-2 cells were divided into blank group， cordycepin group， model group， and H 2 O 2 +cordycepin group. Except for the blank group and cordycepin group， all other groups were treated with 150 μmol/L H 2 O 2 for 72 h to induce persistent oxidative stress injury in cells. After 72 h of cordycepin （40 μmol/L） intervention， the protein and mRNA expression levels of glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4），nuclear factor-erythroid 2-related factor 2（Nrf2）， and heme oxygenase-1 （HO-1） in cells were detected. Furthermore， the Nrf2 inhibitor ML385 was added on the basis of H 2 O 2 +cordycepin to verify the role of the Nrf2/HO-1 pathway. RESULTS Network pharmacology and bioinformatics analysis showed that there were 42 overlapping genes related to AKI-CKD and ferroptosis that interact with cordycepin ferroptosis， among which 38 were annotated as ferroptosis-related genes. HO-1 and Nrf2 might be important targets for cordycepin to inhibit ferroptosis. The binding energies of cordycepin with Nrf2 and HO-1 proteins were －8.5 and －6.7 kcal/mol， respectively. Cell experiments showed that compared with the model group， the protein and mRNA expression levels of GPX4， Nrf2 and HO-1 were significantly increased （ P ＜0.05），while the protein and mRNA expression levels of ACSL4 were significantly decrease d （ P ＜0.05） in the H 2 O 2 +cordycepin group. After the addition of the Nrf2 inhibitor ML385， the effects of cordycepin on the above proteins and mRNA were significantly reversed （ P ＜0.05）. CONCLUSIONS Cordycepin can inhibit ferroptosis by activating the Nrf2/HO-1 pathway， reduce persistent oxidative stress injury of renal tubular epithelial cells， and delay the progression of AKI-CKD.

BACKGROUND:Cannabidiol is effective in ameliorating the body's inflammatory response,but no clear mechanistic studies have been conducted to ameliorate skeletal muscle inflammation induced by exhaustive exercise. OBJECTIVE:To explore the mechanism by which cannabidiol improves skeletal muscle inflammation during exhaustive exercise by using transcriptome sequencing technology. METHODS:Thirty-six Sprague-Dawley rats were randomly divided into six groups:blank control group,exercise coconut oil group,exercise control group,50 mg/kg cannabidiol group,60 mg/kg cannabidiol group,and 70 mg/kg cannabidiol group,with six rats in each group.Except for rats in the blank control group,rats in each group were subjected to swimming exercise for 9 days to produce the exhaustive exercise model.At the end of each swimming exercise,rats in the cannabidiol groups were given 2 mL of fat-soluble cannabidiol at different concentrations(50,60,and 70 mg/kg)by gavage;rats in the exercise coconut oil group were given the same volume of coconut oil by gavage until the end of the exercise on the 9th day;and rats in the blank control group and the exercise control group were not given any special treatment.The levels of inflammatory factors and differentially expressed genes in the skeletal muscle of rats in each group were determined using ELISA and transcriptome sequencing techniques.Differentially expressed genes obtained were subjected to KEGG analysis,and the accuracy of the sequencing data was verified by fluorescence quantitative PCR. RESULTS AND CONCLUSION:The results of ELISA showed that the contents of interleukin-6(P<0.05),tumor necrosis factor-α(P<0.01),interleukin-10 and other inflammatory factors in the exercise group increased significantly compared with the blank control group and the coconut oil group.After cannabidiol intervention,the mass concentrations of interleukin-6 and tumor necrosis factor-α showed a sequential decrease with increasing cannabidiol concentration.By comparing GO and KEGG databases,the functional properties of differentially expressed genes were analyzed,and the results showed that the differentially expressed genes were mainly involved in the tumor necrosis factor signaling pathway and the Toll-like receptor signaling pathway.RT-qPCR results showed that the trends of five randomly selected differentially expressed genes were in agreement with the transcriptome sequencing results.To conclude,cannabidiol can improve skeletal muscle inflammation caused by exhaustive exercise.

The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

Objective To develop and compare prediction models for hyperuricemia(HUA)in perim-enopausal and postmenopausal women using Lasso regression,random forest,and multivariate logistic regres-sion.Methods A multi-stage,stratified cluster sampling method was used to select 12 790 subjects from An-ning City,Yunnan Province.Prediction models for HUA were constructed using Lasso regression,random for-est,and multivariate logistic regression.The efficacy of the model was evaluated by accuracy,sensitivity,speci-ficity,F1 score,and area under the curve(AUC).Results LASSO regression analysis screened 19 variables for inclusion in the model,such as age,waist circumference,diastolic blood pressure,BMI,HDL-C,fasting blood glucose(FBG),etc.The accuracy rate was 0.701,the sensitivity was 0.703,the specificity was 0.680,and the F1 score was 0.806.The AUC(95%CI)was 0.770(0.748-0.792).The results of the random forest model show that variables such as creatinine,triglyceride-glucose index(TyG),TG,BMI,TC,Urea nitrogen(Urea),and ALT were relatively important,with an accuracy rate of 0.663,a sensitivity of 0.653,a specificity of 0.738,and an F1 score of 0.774.The AUC(95%CI)was 0.763(0.741-0.785).Multivariate logistic re-gression results showed that 11 variables including creatinine(Cr),TyG,BMI,Urea,and ALT were included in the model,with an accuracy rate of 0.705,a sensitivity of 0.707,a specificity of 0.686,an F1 score of 0.809,and an AUC(95%CI)of 0.771(0.749-0.793).Conclusion The overall performance of LASSO re-gression and multivariate logistic regression models is better.The random forest model has a strong variable screening ability and high specificity,and can be used as a supplement to provide more accurate predictions.

Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

Pyoderma gangrenosum(PG)is a rare autoinflammatory disease,characterized mainly by painful and necrotic skin ulcers.The etiology of PG is unknown,and its treatment is quite challenging.This article reports a case of recurrent pyoderma gangrenosum successfully treated with adalimumab combined with tofacitinib,along with a review of relevant literature.The patient,a 54-year-old male,presented with scrotal ulcers accompanied by pain for 20 days,worsening and involving the groin area for 5 days,and fever for 1 day.Dermatological examination revealed two painful ulcers on the scrotum with raised edges,clear boundaries,and a small amount of purulent discharge on the surface;the right groin area and the medial left thigh showed irregular infiltrative erythematous plaques,with scattered clustered pustules on them,central necrosis appearing purplish-brown,surrounded by a red halo with clear boundaries.Based on the patient's past medical history,clinical manifestations,and auxiliary examinations,the diagnosis was consistent with pyoderma gangrenosum.After treatment with adalimumab combined with tofacitinib,the patient's symptoms were significantly improved,and the ulcers healed.At the 6-month follow-up,the skin lesions had not recurred.For refractory PG that is ineffective to conventional treatments,adalimumab combined with tofacitinib is an effective and safe treatment option,providing a new combination therapy regimen for PG.

Objective To evaluate the safety and efficacy of transcatheter mitral valve-in-valve replacement(ViV-TMVR)in the treatment of bioprosthetic mitral valve failure.Methods Seventeen patients with bioprosthetic mitral valve failure who required ViV-TMVR were selected.Preoperative data including age,gender,body mass index(BMI),usage time of bioprosthetic mitral valve,comorbidities(hypertension,coronary heart disease,old cerebral infarction,atrial fibrillation and diabetes)and New York Heart Association(NYHA)functional class were recorded,and left ventricular end-diastolic diameter(LVEDD),right atrial diameter(RA),pulmonary artery systolic pressure(PASP),left ventricular ejection fraction(LVEF),type of bioprosthetic mitral valve failure,degree of bioprosthetic mitral valve regurgitation and stenosis,peak velocity and mean transvalvular pressure gradient of the bioprosthetic mitral valve,and Society of Thoracic Surgeons(STS)score were also collected.Intraoperative data included puncture route,valve type,intraoperative complications,operation time and immediate postoperative transesophageal echocardiography(TEE)assessment(peak velocity and mean transvalvular pressure gradient of the valve-in-valve,valve-in-valve regurgitation or paravalvular regurgitation)were collected.Postoperative data included time in the intensive care unit(ICU)/cardiovascular intensive care unit(CCU),total postoperative hospital stay and 30-day postoperative echocardiographic results and NYHA functional class were recorded.Patients were divided into the domestic NewMed valve group(10 cases)and the imported Edwards valve group(7 cases)based on the type of valve used.The safety and efficacy of ViV-TMVR were analyzed,and the efficacy of domestic valves and imported valves was compared.Results All 17 patients successfully underwent ViV-TMVR via the transseptal approach without serious complications,and the 30-day readmission rate was 0%.There were no significant differences in operation time of domestic valves and imported valves,mild paravalvular regurgitation of the valve-in-valve,peak velocity and mean transvalvular pressure gradient of the valve-in-valve immediately after surgery and at 30-day postoperatively,time in ICU/CCU,total postoperative hospital stay and the proportion of patients with NYHA functional class Ⅲ-Ⅳ at 30-day postoperatively between the domestic valve group and the imported valve group.During the 30-day follow-up,one patient died of cerebral hemorrhage,and one patient had major adverse cardiovascular events(MACE,cerebral hemorrhage).Compared with before the operation,the peak velocity and mean transvalvular pressure gradient of the valve-in-valve,LVEF,and PASP decreased immediately after surgery and at 30 days after surgery.Compared with immediately after surgery,the peak velocity and mean transvalvular pressure gradient of the valve-in-valve increased at 30 days postoperatively(P＜0.01),while there were no significant differences in LVEF and PASP.Conclusion Transseptal ViV-TMVR is safe and effective in the short term for patients with bioprosthetic mitral valve failure who are at high risk of re-thoracotomy,and the efficacy of domestic valves is comparable to that of imported valves.