OBJECTIVE To explore the mechanism of improvement effect of Chanbao zhichuang suppository （CBZCS） on hemorrhoids in rats through network pharmacology and metabolomics. METHODS A hemorrhoid model was established by subcutaneous injection of rhododendron oil to induce anal swelling. SD rats were divided into blank group （NC group， 0.32 g/kg vaseline）， model group （Model group， 0.32 g/kg vaseline）， CBZCS low-， medium-， and high-dose groups （CBZCS-L， CBZCS- M， CBZCS-H groups， with dosages of 0.16， 0.32， and 0.64 g/kg respectively）， and Mayinglong musk hemorrhoids suppository group （Positive group， 0.32 g/kg）， with 9 rats in each group. Anal administration was performed at 6， 12， 24， 48， and 72 hours after modeling. After the last administration， the pathological changes of the anal tissues in rats were observed， and the serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in rats were detected. Differential metabolite analysis and enrichment analysis were conducted by metabolomics methods， and the target proteins of CBZCS in treating hemorrhoids were obtained by network pharmacology. The core metabolic pathways were screened by interaction and enrichment analysis of differential metabolites and proteins， and the core proteins were experimentally verified. RESULTS Compared with the NC group， the anal tissues of the Model group showed obvious lesions， and the levels of IL-6 and TNF- α in the serum were significantly increased （P＜0.05）； compared with the Model group， the pathological damage of the anal tissues in the treatment groups was alleviated to varying degrees， and serum levels of IL-6 in CBZCS-H group， CBZCS-M group， and Positive group as well as serum levels of TNF-α in CBZCS-H group were significantly reduced （P＜0.05）. The metabolomics results showed that 34 differential metabolites were screened from the anal tissues of rats， and 22 of them showed a return after CBZCS administration. The differential metabolites mainly enriched in arachidonic acid metabolism， histidine metabolism， and glycerophospholipid metabolism. Through the network pharmacology， 138 intersection genes of CBZCS against hemorrhoids were determined. The analysis results showed that differential metabolites and target proteins were mainly enriched in the arachidonic acid metabolism pathway， and the regulation of this pathway might be related to cyclooxygenase-2 （COX-2）， Myc proto-oncogene protein （c-MYC）， cytochrome P450 1B1 （CYP1B1）， interleukin-1β （IL-1β）， and IL-6 protein expression. The experimental verification results showed that the expression levels of key proteins （COX-2， c-MYC， CYP1B1， IL-6， IL-1β） in the anal tissues of the Model group were significantly higher than those in the NC group （P＜0.05）， and the levels of the above proteins in the anal tissues of CBZCS-H group and Positive group were significantly lower than those in the Model group （P＜0.05）. CONCLUSIONS The mechanism of CBZCS in treating hemorrhoids may be to inhibit the expression of COX-2， c-MYC and CYP1B1 proteins， thereby inhibiting arachidonic acid metabolism and reducing the release of inflammatory factors IL-6 and IL-1β.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of Lewy bodies, leading to motor and nonmotor symptoms. While both genetic and environmental factors contribute to PD, recent studies highlight the crucial role of lipid metabolism disturbances in disease progression. Altered lipid homeostasis promotes protein aggregation and oxidative stress, with significant changes in lipid classes such as sphingolipids and glycerolipids observed in patients with PD. These disturbances are involved in key pathological processes, such as α-synuclein aggregation, organelle dysfunction, lipid-mediated neuroinflammation, and impaired lipid homeostasis. This review examines the relationship between lipid species and PD progression, focusing on the physiological roles of lipids in the central nervous system. It explores the mechanistic links between lipid metabolism and PD pathology, along with lipid-related genetic risk factors. Furthermore, this review discusses lipid-targeting therapeutic strategies to mitigate PD progression, emphasizing the potential of lipid modulation for effective treatment development.
Humans ; Parkinson Disease/metabolism* ; Lipid Metabolism/physiology* ; Animals ; Oxidative Stress/physiology* ; alpha-Synuclein/metabolism*

BACKGROUND: Parkinson's disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data. METHODS: Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes. RESULTS: GBD 2021 estimated 508,378 (95% UI: 430,499-592,748) incident cases of PD, 92,035 (95% UI: 75,908-108,133) deaths, and 2,159,514 (95% UI: 1,826,196-2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004-2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. CONCLUSIONS The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.
Humans ; Parkinson Disease/mortality* ; China/epidemiology* ; Global Burden of Disease ; Male ; Incidence ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Quality-Adjusted Life Years ; Aged, 80 and over ; Cost of Illness ; Adolescent ; Pattern Analysis, Machine

ObjectiveTo conduct comprehensive assessment of internal and external cadmium exposure and health risks for Shanghai residents. MethodsCadmium levels in food samples were calculated by employing two dietary exposure assessment methods， total diet study （TDS） and food frequency questionnaire （FFQ）， to estimate the daily dietary cadmium exposure of Shanghai residents. The provisional tolerable monthly intake （PTMI） of cadmium set by joint food and agriculture organization/WHO expert committee on food additives （JECFA） was applied to evaluate the health risk. Differences in dietary and urinary cadmium were compared by rank-sum test among different regions， age， gender， smoking status， and BMI groups， and the association between internal and external cadmium exposure was investigated by correlation analysis. ResultsThe mean value of urinary cadmium for 1 300 respondents was 0.542 μg·L^-1. Urinary cadmium was higher in the population in central urban and urban-rural fringe areas than in the suburban area， higher in the older age group than in the younger age group， and higher in the smoking group than in the non-smoking group （all P<0.01）. The two assessment methods showed that the mean values of daily dietary cadmium exposure for Shanghai residents were 0.306 and 0.090 μg·kg^-1， with 3.69% and 0.85% of Shanghai residents exceeding the PTMI， respectively. Correlation analyses showed that dietary exposure to cadmium based on the FFQ method was positively correlated with the urinary cadmium level when smoking status， age， gender， and BMI were adjusted. ConclusionDietary exposure to cadmium of Shanghai residents is mainly derived from vegetables， aquatic products， cereals and potatoes， and is overall at a low-risk level. Dietary exposure assessment based on FFQ and risk monitoring data can effectively estimate long-term cadmium exposure.

Viral sepsis is an often neglected heterogeneous form of sepsis，which can be caused by a variety of viruses.Infants and young children are at high risk of viral sepsis，which is related to their relatively low immunity.Viral sepsis is different from bacterial infection in terms of pathogenesis，clinical phenotype,and treatment strategy.Effective elimination of virus and immune regulation according to different immune types may be beneficial to improve the prognosis.

Sepsis-induced thrombocytopenia-associated multiple organ failure（TAMOF）is a severe subtype of sepsis-related organ dysfunctions，which has high mortality and poor prognosis.The main clinical characteristics are thrombocytopenia caused by infection and multiple organ dysfunction.However，the exact molecular mechanism of TAMOF remains unclear.The current studies have shown ADAMTS-13，which is a von Willebrand factor lyase，plays an important role during the disease.Plasma exchange could be a treatment method，but still need more large-scale randomized controlled trials to verify.In the future，von Willebrand factor and ADAMTS-13 could become the therapeutic targets for new drug development.

Augmented renal clearance（ARC）can be caused by the disease itself，inflammatory state，or therapeutic interventions，and is often associated with severe infections and trauma.Sepsis is one of the most important diseases with high morbidity and mortality in the world.Current studies suggest that ARC is significantly associated with inadequate antimicrobial therapy concentration in patients with sepsis，increasing the risk of clinical treatment failure.It is important to optimize the drug administration strategy for patients with ARC in sepsis，although the current clinical screening of ARC is not yet perfect.This review summarized the literature on changes in blood concentration of antibiotics and administration strategies in patients with sepsis with ARC，in order to provide appropriate medication and clinical guidance for ARC patients.

Objective To explore the changes in cerebral blood flow caused by mandibular retrusion,as well as the impact and potential mechanisms on stroke recovery.Methods 6-week-old SD male rats were selected as experi-mental subjects.The metal cannula was bonded to the rat maxillary incisor for one week,forcing mandibular retru-sion(MR).Cerebral blood flow was detected by laser speckle imaging.Cognitive function was detected by the Morris water.Then,the stroke model was constructed in MR rats by using the middle cerebral artery occlusion(MCAO)method for one week.Meanwhile,metal cannulae were then removed in rats to restore the lower jaw's position(MCAO RO),serving as a positive control group.Consequently,rats were randomly divided into the fol-lowing groups:Sham groups,MCAO groups,MCAO MR groups,and MCAO RO groups.Neurological recovery was assessed through the modified neurological severity score(mNSS).The area of cerebral infarction was evalua-ted by using triphenyltetrazolium(TTC)staining.The changes in nerve cells were observed by using hematoxylin eosin(HE)staining.The protein expression level of vascular endothelial growth factor(VEGF)was detected by immunohistochemistry.The protein expression levels of platelet-endothelial cell adhesion molecule(CD31),sirtuin 6(SIRT6),and thioredoxin interaction protein(TXNIP)were detected by Western blot.The mRNA expression levels of SIRT6,TXNIP,and VEGF were determined by qRT-PCR.Microglia activation marker molecule 1(IBA-1)was detected by immunofluorescence.Resluts Because of mandibular retrusion,laser speckle showed de-creased cerebral blood flow,and the water maze showed decreased cognitive function.Compared to other groups,MCAO MR showed a larger ischemic area in TTC staining,while HE staining and neurological scoring showed poo-rer neurological function recovery.Western blot and qRT-PCR showed that the MCAO MR group inhibited the mR-NA and protein expression levels of SIRT6,upregulated the mRNA and protein expression levels of TXNIP,and in-creased the activation of microglia.Conclusion Mandibular retrusion reduces cerebral blood flow and alters cogni-tive function in rats.Mandibular retrusion inhibits recovery in stroke through the SIRT6/TXNIP axis.

Objective:To analyze assessment value of the hemodynamics of posterior cerebral artery(PCA)detected by transcranial color-coded Doppler(TCCD)ultrasound for occurring cerebral infarction in patients with fetal-type posterior cerebral artery(FTP).Methods:A total of 300 patients with suspected cerebrovascular disease admitted to the Department of Neurology of The Second Hospital of Harbin City from January,2020 to December 31,2023 were retrospectively selected.In these patients,7 cases with cerebral hemorrhage(without complication of cerebral infarction)did not be included.According to the clinical manifestations and the results of imaging examination,293 patients were divided into transient ischemic attack(TIA)group(176 cases)and acute ischemic stroke(AIS)group(117 cases).The differences in FTP detection between TCCD examination and magnetic resonance angiography(MRA)were compared.The differences in PCA hemodynamics among TIA,anterior circulation infarction,posterior circulation infarction and lacunar infarction were compared.The proportions of patients with TIA,anterior circulation infarction,posterior circulation infarction and lacunar infarction combined with FTP were also compared,and the PCA hemodynamics of patients with posterior circulation infarction of bilateral cFTP,unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP were compared.The proportions of patients with transient ischemic attack(TIA)who occurring AIS at bilateral cFTP,unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP in short term were compared.The receiver operating characteristic(ROC)curve and area under curve(AUC)were used to assess the predictive value of abnormal PCA hemodynamics of TIA patients,who combined with and/or without FTP,occurred AIS in short term.Results:MRA revealed that a total of 89 patients combined with FTP in 293 patients,of which 14 cases were bilateral cFTP(accounting for 15.73%),and 25 cases were unilateral cFTP(accounting for 28.09%),and 8 cases were bilateral pFTP(accounting for 8.99%),and 42 cases were unilateral pFTP(accounting for 4 7.19%).According to TCCD testing,it was found that a total of 89 cases combined with FTP in 293 patients,of which 16 cases were bilateral cFTP(accounting for 17.98%),and 23 cases were unilateral cFTP(accounting for 25.84%),and 8 cases were bilateral pFTP(accounting for 8.99%),and 42 cases were unilateral pFTP(accounting for 47.19%).There was favorable consistency between TCCD and MRA(Kappa=0.899).Under TCCD,the blood flow velocity(Vp)and resistance index(RI)of systolic stage of PCA in patients with posterior circulation infarction were significantly higher than those in patients with TIA,anterior circulation infarction,and lacunar cerebral infarction(F=15.392,9.032,P<0.05),respectively.Patients with posterior circulation infarction were more likely to occur bilateral cFTP.The Vp,Vm and Vd of patients with bilateral cFTP were significantly higher than those of patients with bilateral pFTP,unilateral pFTP and non-FTP(F=14.932,8.884,6.054,P<0.05),respectively.The proportion of occurring AIS in TIA patients with bilateral cFTP was significantly higher than that in TIA patients with unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP(Z=6.883,7.568,6.253,6.772,P<0.05),and the proportions of occurring AIS in TIA patients with unilateral cFTP,bilateral pFTP and unilateral pFTP were significantly higher than that in TIA patients with nFTP(Z=5.986,6.877,6.856,P<0.05),respectively.A total of 45 cases(accounting for 25.57%)of 176 TIA patients occurred AAIS within 3 months after they discharged.The AUC value of predictive value of Vp for occurring AIS in 45 TIA patients with FTP was 0.818,which was significantly higher than that(AUC=0.589)for occurring AIS in 131 TIA patients with non-FTP.Conclusion:Patients with posterior circulation cerebral infarction are prone to occur PCA hemodynamic abnormalities.In patients with posterior circulation infarction,the PCA blood flow velocity in patients with bilateral cFTP significantly accelerates.PCA hemodynamic ultrasound examination has a certain of predictive value for occurring AIS in short term in TIA patients who combine with FTP.

Objective:To investigate the clinical effects of Ortho-Bridge system in the treatment of scapular fractures.Methods:A retrospective analysis was performed for the 23 patients with scapular fracture who had been treated with Ortho-Bridge system and followed up completely at Department of Orthopedics, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine from May 2020 to May 2023. They were 19 males and 4 females with an age of (40.3±11.6) years. The modified Judet approach was adopted in 9 cases and minimally invasive approach in 14 cases in the surgery. The time from injury to surgery was 3.0 (0, 4.0) days. Related perioperative indicators were recorded, including surgery time, intraoperative bleeding, postoperative complications, and fracture healing time. Postoperatively, Constant shoulder score (CSS) and the quick disabilities of the arm, shoulder and hand (quickDASH) were used to quantify the postoperative efficacy.Results:All the 23 patients were followed up for (30.1±12.0) months. The surgery time averaged (136.3±32.0) minutes and the intraoperative bleeding (178.3±50.3) mL. The rate of postoperative fracture healing was 100% (23/23), and the fracture healing time 4.0 (3.0, 4.0) months. After surgery, one patient developed superficial infection which was cured by oral antibiotics and dressing change. No other adverse complications occurred. The CSS of the shoulder at the last follow-up was (91.7±3.0) points. The quickDASH score of the upper limb function at the last follow-up averaged (10.4±3.6) points, giving an excellent to good rate of 91.3% (21/23).Conclusion:In the treatment of scapular fractures, internal fixation with Ortho-Bridge system can result in excellent clinical effects and a low incidence of postoperative complications, because it is simple to handle, limitedly traumatic, flexible and versatile in combination of internal fixation and very personalized.