ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.

OBJECTIVE To analyze the impact of the diagnosis-related groups （DRG） payment reform on the length of stay and medical costs in patients with chronic obstructive pulmonary disease （COPD） in Kashgar region， aiming to provide localized empirical evidence for the optimization of regional medical insurance payment methods. METHODS Based on the inpatient settlement database of the Xinjiang Uygur Autonomous Region Healthcare Security Administration， settlement data of COPD inpatients from 17 medical institutions in Kashgar region between January 1， 2022， and December 31， 2024， were extracted. The overall changes in patients’ length of stay and costs were compared before and after the reform. Subsequently， interrupted time series analysis （ITSA） was employed to explore the impact of the DRG payment reform on these variables. RESULTS Following the reform， both the average length of stay and various cost decreased significantly compared to the pre-reform period （ P ＜0.001）. At the overall sample level， the average length of stay， average total cost， average drug cost， average medical service cost， and average examination cost per admission all demonstrated significant long-term downward trends after the reform （ P ＜0.05）. However， the decrease in average out-of-pocket costs and the increase in average consumable costs per admission were not statistically significant （ P ＞0.05）. In tertiary medical institutions， the average length of stay and all categories of costs （except average consumable costs per admission） exhibited significant long-term upward trends after the reform （ P ＜0.05）； conversely， in secondary and lower-level medical institutions， the average length of stay， average total cost， average drug cost， average medical service cost， and average examination cost per admission showed significant long-term downward trends （ P ＜0.05）. CONCLUSIONS The DRG payment reform has achieved an overall effect of reducing the length of stay and controlling costs in COPD patients from Kashgar region. However， the effects vary across different levels of medical institutions： secondary and lower-level institutions show a long-term downward trend in length of stay and costs， whereas tertiary institutions exhibit a long-term upward trend. Furthermore， patients’ out-of-pocket financial burden does not show significant improvement.

This paper summarizes Professor WANG Yaoxian's experience in treating diabetic kidney disease （DKD） from the perspective of spleen and stomach based on the "internal heat leading to concretions" theory. It is considered that internal heat leading to concretions constitutes the core pathogenesis of DKD， with the spleen and stomach serving as the source of internal heat； therefore， treatment should be based on regulating the spleen and stomach. In the early stage of DKD， dysfunction of the spleen and stomach leads to the initial generation of internal heat. Common syndrome patterns include gastrointestinal heat accumulation and constrained heat in the liver and stomach， for which modified Gegen Qinlian Decoction （葛根芩连汤） can be used to clear heat bind while modified Dachaihu Decoction （大柴胡汤） is used to clear stomach and soothe liver， respectively. In the middle stage of DKD， weakness of the spleen and stomach results in the initial formation of concretions and conglomerations. Common patterns include spleen deficiency with prevalence of dampness and deficiency of both the spleen and kidney. Treatment emphasizes strengthening the spleen and resolving dampness， raising yang and boosting the stomach with modified Shengyang Yiwei Decoction （升阳益胃汤）， or supplementing spleen and boosting kidney， dissipating bind and dispe-ring concretions with modified Shenqi Dihuang Decoction （参芪地黄汤）， respectively. In the late stage of DKD， it is characterized by spleen and stomach depletion， and rampant accumulation of turbidity and toxin， and the common syndrome patterns are damp-turbidity obstruction in the middle jiao （焦） and spleen-kidney yang deficiency. Treatment aims to remove turbidity and harmonize the stomach， or to warm the kidney and strengthen the spleen while elimina-ting turbidity， using modified Dahuang Gancao Decoction（大黄甘草汤） and Jupi Zhuru Decoction （橘皮竹茹汤） or modified Baoyuan Decoction （保元汤） and Lizhong Decoction （理中汤）， respectively. In clinical practice， appropriate formulas and medications are flexibly selected according to specific syndromes.

ObjectiveTo investigate the efficacy of C-reactive protein （CRP） in predicting the progression to acute-on-chronic liver failure （ACLF） within 90 days after disease onset in patients with acute decompensation （AD） of cirrhosis， and to provide a reference for the early identification of high-risk populations in clinical practice. MethodsA retrospective study was conducted among 906 patients with liver cirrhosis who were hospitalized due to AD in Nanjing Second Hospital from January 1， 2015 to October 31， 2024， and demographic features， AD type， and laboratory markers were collected on admission. The primary endpoint was progression to ACLF within 90 days after admission， and according to the presence or absence of ACLF， the patients were divided into non-ACLF group with 676 patients and ACLF group with 230 patients. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Cox proportional-hazards regression models were used to identify independent predictive factors for ACLF. The receiver operating characteristic （ROC） curve was used to assess the predictive performance of CRP and existing scoring systems （Model for End-Stage Liver Disease ［MELD］， Child-Turcotte-Pugh ［CTP］ score， and Chronic Liver Failure Consortium Acute Decompensation ［CLIF-C AD］ score）， and the restricted cubic spline analysis was used to investigate the nonlinear relationship between CRP and the risk of ACLF. Youden index was used to determine the optimal predictive cut-off value for CRP， and the Kaplan-Meier survival curve was plotted for risk stratification， while the log-rank test was used for survival analysis. ResultsAmong the 906 AD patients， the incidence rate of ACLF was 25.39% within 90 days. The incidence rate of ACLF within 90 days was 45.1% in the 264 patients with bacterial infection and 17.3% in the 642 patients without bacterial infection （χ²=74.791， P<0.001）. Among the 906 patients， 312 patients （34.44%） had acute-on-chronic pre-liver failure （pre-ACLF）， with a significantly higher proportion of patients who progressed to ACLF than those in the non-pre-ACLF group ［60.58% （189/312） vs 6.90% （41/594）， χ²=310.234， P<0.001］. Among the 230 patients with ACLF， there were 102 patients with stable ACLF （44.35%） and 128 patients with unstable ACLF （55.65%）， with a significant difference in CRP between the two groups of patients （U=5 234.500， P<0.001）. The restricted cubic spline analysis showed a significant nonlinear relationship between CRP and the risk of ACLF （P<0.001）. The optimal cut-off value of CRP was determined as 10.16 mg/L based on the Youden index， with a sensitivity of 70.4% and a specificity of 64.5%. The Kaplan-Meier curve analysis showed that the high-risk group with CRP≥10.16 mg/L had a significantly higher event-free survival rate of ACLF within 90 days compared with the low-risk group （P<0.001）. The multivariate Cox regression analysis showed that AD type-hepatic encephalopathy （hazard ratio ［HR］=4.199， 95% confidence interval ［CI］： 3.056 — 5.770， P<0.001）， AD type-bacterial infection （HR=1.826， 95%CI： 1.356 — 2.459， P<0.001）， CRP （≥10.16 mg/L） （HR=2.356， 95%CI： 1.825 — 3.047， P<0.001）， white blood cell count （HR=1.021， 95%CI： 1.002 — 1.041， P=0.035）， hemoglobin （HR=0.994， 95%CI： 0.989 — 0.999， P=0.025）， international normalized ratio （HR=1.657， 95%CI： 1.372 — 2.001， P<0.001）， total bilirubin （HR=1.003， 95%CI： 1.002 — 1.004， P<0.001）， albumin （HR=0.956， 95%CI： 0.926 — 0.986， P=0.004）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， serum sodium （HR=0.976， 95%CI： 0.956 — 0.997， P=0.025）， and lactate dehydrogenase （HR=1.001， 95%CI： 1.001 — 1.002， P<0.001） were all independent predictive factors for progression to ACLF within 90 days. The ROC curve analysis showed that CRP alone had an area under the ROC curve （AUC） of 0.724 （95%CI： 0.685 — 0.763） in predicting ACLF， and CRP+MELD score had the best predictive performance （AUC=0.870， 95%CI： 0.843 — 0.898）， while CRP+CTP score and CRP+CLIF-C AD score had an AUC of 0.852 （95%CI： 0.823 — 0.881） and 0.845 （95%CI： 0.812 — 0.877）， respectively. There was a significant increase in model performance after integration （P<0.05）. ConclusionSerum CRP level on admission is an independent predictive factor for progression to ACLF within 90 days in patients with AD of cirrhosis， and a CRP level of ≥10.16 mg/L can be used as a simple threshold for identifying high-risk patients. Incorporating CRP into existing assessment systems may enhance the early identification of patients at a high risk for ACLF， which provides a reference for clinical intervention.

The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

OBJECTIVE: To report the clinical experience of using Ilizarov wrist joint distraction technique in the treatment of a case of rheumatoid arthritis of the wrist. METHODS: In January 2019, a 49-year-old female patient with rheumatoid arthritis of the left wrist, complicated by ulnar impaction syndrome, was admitted for treatment. Preoperatively, the active range of motion of the left wrist was as follows: extension 0°-flexion 0°, pronation 65°-supination 35°, and grip strength of 4.0 kg. The visual analogue scale (VAS) score was 9, and the Cooney wrist function score was 15, indicating poor function. As conservative treatment failed to achieve symptom relief, Ilizarov wrist joint distraction surgery was performed. Postoperatively, joint distraction was applied at 2 mm increments on postoperative days 2 and 7, in 4 separate sessions. RESULTS: Postoperative X-ray film examination at 7 days revealed a distraction of 3.6 mm in the affected wrist joint compared to the contralateral side. The external fixator was removed 2.5 months postoperatively. At 22 months postoperatively, X-ray film and MRI examinations revealed that the joint space of the left wrist had returned to near-normal, with significant reduction in joint effusion and synovial proliferation. The active range of motion of the left wrist improved to extension 15°- flexion 30°, pronation 90°-supination 90°, with a grip strength of 18.0 kg. The wrist pain VAS score decreased to 0, and the Cooney wrist function score improved to 90, indicating excellent function. At 50 months postoperatively, follow-up X-ray film, MRI, and functional assessments showed the results similar to those at 22 months. CONCLUSION Ilizarov wrist joint distraction may be a viable treatment option for rheumatoid arthritis of the wrist.
Humans ; Female ; Middle Aged ; Wrist Joint/physiopathology* ; Arthritis, Rheumatoid/physiopathology* ; Range of Motion, Articular ; Ilizarov Technique ; Treatment Outcome ; Osteogenesis, Distraction/methods*

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

OBJECTIVE: Coptis chinensis (Huanglian in Chinese, HL) is commonly utilized in clinical settings to counteract dyslipidemia in patients with hot syndrome. Its lipid-reducing efficacy has been consistently demonstrated in high-fat diet (HFD)-induced hyperlipidemic animal models. However, whether HL's efficacy differs in HFD-fed animals with hot or cold syndromes remains unclear. This study aims to discern the variations in the anti-hyperlipidemic effects of HL in HFD-fed mice with hot or cold syndromes. METHODS: HFD-induced C57BL/6 mice were subjected to cold or hot syndrome via two weeks of ice water (0 °C) and levothyroxine sodium (240 µg/kg) treatment, respectively. Then, an aqueous extract of HL was administered to the mice via oral gavage over the following four-week period. Lipid levels in the serum and liver were gauged to determine the lipid-reducing effects of HL. Furthermore, gut microbiota composition was elucidated using full-length 16S rRNA gene sequencing. RESULTS: HL notably reduced lipid levels in HFD-induced hyperlipidemic mice. Its efficacy was amplified in hyperlipidemic mice with a hot syndrome but was markedly reduced in those with a cold syndrome. HL treatment led to a decline in alpha-diversity (characterized by ACE, Chao1, Shannon and Simpson index) of the gut microbiota in both sets of mice but affected specific microbial populations based on the syndrome. Specifically, while HL led to a notable increase in Eubacterium, Robinsoniella, and Lachnoclostridium genera, along with the enhancement of Clostridium innocuum and Bacteroides thetaiotaomicron species across all conditions, it syndrome-dependently stimulated Romboutsia ilealis and Parabaceroides_sp_HGS0025 species in mice with hot syndrome. CONCLUSION HL shows stronger lipid-lowering effect on hyperlipidemic mice with hot syndrome, which is in accordance with its traditional usage in clinic. The therapeutic outcomes of HL are intrinsically tied, at least in part, to its modulatory effects on the gut microbiota, offering fresh insights into the foundational principles of traditional Chinese medicine.

Objective To explore the effect of diet therapy on alcohol-induced chronic liver injury in rats and its relationship with TLR4 pathway.Methods According to Pueraria:Poria:Amomum villosum:Pericarpium Citri Reticulatae:Codonopsis:Zingiberis Rhizoma=15∶15∶10∶10∶10∶6,the water extract of the therapeutic prescription was prepared.A total of 78 female SD rats were randomly divided into 6 groups:normal group(n=12),model group(n=18),Hugan tablet group(0.35 g·kg-1,n=12),low-,medium-and high-dose Shiliaofang groups(2,6,18 g·kg-1,n=12).Except for the normal group,the rats in each group were induced alcoholic liver disease(ALD)by gradient alcohol gavage.After 10 weeks of intervention,the changes of body weight and water intake of rats were observed.The whole blood routine,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC)and liver malondialdehyde(MDA)were measured.The levels of serum alcohol dehydrogenase(ADH),aldehyde dehydrogenase(ALDH),lipopolysaccharide(LPS),D-lactic acid(D-LA),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay.HE staining was used to observe the pathological changes of liver and ileum.Oil red staining was used to observe liver fat deposition.Immunohistochemistry was used to detect the expression of ileal tight junction component occludin.Western blot was used to detect the expression of TLR4,MyD88 and NF-κB p65 protein in liver.Results Compared with the model group,the levels of WBC,LYC,TC,ALT,AST,LPS,D-LA,TNF-α and IL-6 in each diet group decreased,IL-10 increased,liver inflammatory cell infiltration and red lipid droplets decreased,intestinal villi were intact and densely arranged,the expression of occludin protein in ileum increased,and the expression of TLR4,MyD88 and NF-κB p65 protein in liver decreased.Conclusion The self-made dietotherapy prescription has a significant protective effect on chronic liver injury induced by alcohol in rats,which may be related to its down-regulation of TLR4-MyD88-NF-κB p65 protein expression and up-regulation of ileal occludin protein expression,improvement of intestinal mucosal barrier function,reduction of endotoxin entry into the liver,activation of TLR4/MyD88/NF-κB pathway,thereby reducing the second hit to the liver.This diet can be developed as a potential anti-alcoholic liver injury drug.