Parkinson's disease （PD） is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra， abnormal aggregation of alpha-Synuclein （α-Syn）， and the formation of Lewy bodies. However， the exact mechanisms remain unclear. In recent years， the PD incidence has gradually increased， while current treatment methods are limited to symptom alleviation， incapable of halting disease progression， and prone to adverse effects， thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is closely related to oxidative stress， neuroinflammation， apoptosis， ferroptosis， and mitochondrial dysfunction， playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine （TCM） can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages， such as multiple targets， multiple pathways， and fewer adverse reactions， TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD， while summarizing the latest research on PD intervention by TCM monomers， active ingredients， and compounds， as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway， aiming to provide a reference for clinical medicine development to prevent and treat PD.

ObjectiveTo investigate the efficacy of selective internal radiation therapy （SIRT） in patients with unresectable hepatocellular carcinoma， and to provide a reference for the selection of clinical treatment regimens. MethodsA retrospective analysis was performed for the clinical data of 73 patients with unresectable hepatocellular carcinoma who received yttrium-90 microsphere SIRT in Eastern Hepatobiliary Surgery Hospital from May 1， 2023 to September 1， 2024. According to tumor characteristics， physical status， liver reserve function， laboratory tests， and SIRT treatment strategy， the patients were divided into radiation segmentectomy group with 9 patients， conversion therapy group with 47 patients， and palliative treatment group with 17 patients. Based on the results of postoperative follow-up， modified Response Evaluation Criteria in Solid Tumors were used to assess radiographic images. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the chi-square test was used for comparison of categorical data between three groups； the Logistic regression model was used to perform the multivariate analysis. ResultsThere was a significant difference in postoperative outcome between the radiation segmentectomy group， the conversion therapy group， and the palliative treatment group （χ²=30.060， P<0.001）. The disease control rate was 100.0% （9/9） in the radiation segmentectomy group， 83.0% （39/47） in the conversion therapy group， and 29.4% （5/17） in the palliative treatment group， with a significant difference between the three groups （χ²=19.575， P<0.001）， and there was also a significant difference in objective response rate between the three groups （χ²=17.749， P<0.001）. The multivariate Logistic regression analysis showed that the number of tumors （odds ratio ［OR］=0.085， 95% confidence interval ［CI］： 0.008 — 0.906， P=0.041） and combined targeted immunotherapy （OR=18.808， 95%CI： 1.704 — 207.616， P=0.017） were independent influencing factors for achieving complete response. ConclusionThe number of tumors is an independent influencing factor for the efficacy of SIRT and is an important basis for selecting different treatment goals. SIRT combined with targeted immunotherapy may achieve better efficacy.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital bilateral malformation of the large toe and progressive, extensive, and irreversible heterotopic ossification (HO) of soft tissues throughout the body, leading to severe disabilities. FOP is caused primarily by mutations in activin A receptor type 1 (ACVR1), also known as activin-like kinase 2 (ALK2), which encodes a receptor belonging to the bone morphogenetic protein (BMP) type I family. However, the continuous and complex process of HO in FOP is not yet fully understood, which has impeded the development of therapeutic drugs. Despite surgical removal of HO, which often results in recurrence and expansion of ossification, there is currently no definitive drug treatment available to completely prevent, halt, or reverse the progression of HO in FOP. Currently, researchers are intensively studying the pathogenesis of FOP at various stages and developing promising drug candidates, including saracatinib, palovarotene, and rapamycin. This review provides an overview of progress in understanding the mechanism of FOP and the development of therapeutic drugs, with the goal of providing insights for further research and the development of new treatment methods.
Myositis Ossificans/genetics* ; Humans ; Activin Receptors, Type I/genetics* ; Ossification, Heterotopic ; Mutation ; Sirolimus/therapeutic use* ; Quinolones/therapeutic use* ; Benzodioxoles/therapeutic use* ; Animals ; Quinazolines/therapeutic use*

Point-of-care testing (POCT) provides key support for clinical decision-making through rapid detection. This article introduces the development background of POCT in the field of pre-hospital emergency, as well as the development status of POCT in Hangzhou City, and analyzes the problems of quality management. Pre-hospital emergency medical institutions in Hangzhou City have been equipped with POCT equipment, and the test items include blood glucose, cardiac troponin, etc. The implementation rates of internal quality control, comparison test, and proficiency testing were 58.2%, 50.3% and 42.6%, respectively. POCT quality management has problems such as unclear responsibility subjects, insufficient professional personnel, and a lack of standardization of the process. It is proposed to build a hierarchical collaborative management system, strengthen the double access mechanism of personnel and equipment, implement the whole process quality control, and build a digital management platform, so as to provide the reference for the high-quality development of POCT in pre-hospital medical emergency institutions.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

Objective:To develop and validate a predictive model for massive hemorrhage during brain tumor resection in pediatric patients.Methods:A retrospective analysis was performed on the clinical data from pediatric patients who underwent elective brain tumor resection under general anesthesia at the Women and Children′s Medical Center Affiliated to Guangzhou Medical University from December 2016 to October 2023. The patients were randomly divided into model group and internal validation group in a ratio of 8∶2. Pediatric patients who underwent elective brain tumor resection under general anesthesia at Qilu Hospital of Shandong University from January 2021 to July 2024 were selected and served as external validation group. Relevant characteristic variables were screened through Lasso regression. A multivariate logistic regression was used to develop the model and plot the nomogram for intraoperative massive hemorrhage. The performance of the model was evaluated using the area under the receiver operating characteristic curve and calibration curve.Results:Through Lasso regression and multivariate logistic regression analyses, 11 independent influencing factors were identified: age ( OR=0.323, 95% confidence interval [ CI]: 0.280-0.374, P<0.001), weight ( OR=0.164, 95% CI: 0.135-0.199, P<0.001), activated partial thromboplastin time ( OR=1.133, 95% CI: 1.036-1.239, P=0.006), thrombin time ( OR=1.141, 95% CI: 1.048-1.243, P=0.002), red blood cell count ( OR=0.941, 95% CI: 0.888-0.996, P=0.035), hemoglobin concentration ( OR=0.873, 95% CI: 0.822-0.926, P<0.001), platelet count ( OR=1.062, 95% CI: 1.001-1.127, P=0.048), maximum tumor diameter ( OR=2.384, 95% CI: 2.241-2.536, P<0.001), tumor invasiveness ( OR=2.376, 95% CI: 2.071-2.726, P<0.001), hydrocephalus ( OR=2.409, 95% CI: 2.139-2.713, P<0.001), and centered midline structure ( OR=0.509, 95% CI: 0.465-0.557, P<0.001). Based on this, a nomogram prediction model was established. The receiver operating characteristic curve showed that the area under the curve of this model in predicting the risk of massive hemorrhage during brain tumor resection was 0.936 (95% CI: 0.90-0.959) in model group, 0.863 (95% CI: 0.744-0.948) in internal validation group, and 0.855 (95% CI: 0.726-0.955) in external validation group. The calibration curve indicated good model consistency, and the Hosmer-Lemeshow goodness-of-fit test result showed a P value of 0.979 ( P>0.05). Conclusions:Age, body weight, activated partial thromboplastin time, thrombin time, red blood cell count, hemoglobin concentration, platelet count, maximum tumor diameter, tumor invasiveness, hydrocephalus and midline structure are independent influencing factors for major bleeding during brain tumor resection in pediatric patients, and the prediction model established based on this histogram has high accuracy.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective To investigate the associations between unilateral or bilateral hearing loss and 12 chronic diseases as well as multimorbidity among the oldest old in China,and to identify disparities in these associations of left-and right-side hearing loss with chronic diseases.Methods Totally 7 437 people aged ≥80 years old were selected from the Chinese Longitudinal Health and Longevity Survey(CLHLS)2018 cross-sectional data.With 12 chronic diseases and multimorbidity as outcome variables,the hearing loss as explanatory variable,socio-demographic characteristics,family factors,and lifestyle as covariates,the correlations of unilateral(left-or right-side)and bilateral hearing loss with chronic diseases and multimorbidity were analyzed using multivariate logistic regression model,and the trend analyses were carried out.Results There were 205(2.76％),227(3.05％)and 3 598(48.38％)old people with left-side,right-side and bilateral hearing loss,respectively.After adjusting for confounders,the oldest old with left-sided or bilateral hearing loss had a greater risk of multimorbidity compared with those with normal hearing function,with odds ratio(95％confidence interval)of 2.14(1.58-2.90)and 1.27(1.13-1.43),respectively,while no association between right-sided hearing loss and multimorbidity was observed(P＞0.05).Trend analysis showed that the risk of multimorbidity increased with hearing loss from none to unilateral and then to bilateral(P＜0.001).Conclusion Hearing loss may be related to the increased risk of multimorbidity in the oldest old,and the risk of those with bilateral hearing loss is higher.More attention should be paid to the prevention and treatment of hearing loss in the oldest old.

Objective To investigate the epidemiological characteristics of patients with postcraniotomy meningitis(PM)caused by Gram-negative bacteria(GNB),and to evaluate the related risk factors for mortal-ity.Methods A total of 202 PM patients in Beijing Tiantan Hospital,Capital Medical University from May 2019 to December 2021 were retrospectively analyzed,including 54 cases in the death group and 148 cases in the survival group.The distribution of microorganisms in the two groups was analyzed,and Cox proportional hazards regression model was established to evaluate the risk factors of death.Results Among the 202 pa-tients with PM caused by GNB,with a mortality rate of 26.7%,Klebsiella pneumoniae(24.8%),Acinetobact-er baumannii(21.8%)and Escherichia coli(8.4%)were the top three isolated pathogens.The proportions of GNB distribution in the survival group and the death group were similar,but the bacteria distribution in the death group was more concentrate.Cox proportional hazards regression model results showed that hyperten-sion(HR=2.384,95%CI 1.229-4.626,P=0.010)and admission to ICU(HR=3.695,95%CI 1.412-9.670,P=0.008)were independent risk factors for death in patients with PM caused by GNB.Conclusion The mortality of PM caused by GNB is high.Hypertension and admission to ICU are independent risk factors for death of patients,and attention should be paid to prevention and treatment in clinical practice.