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.

Objective:To investigate the effects of stem cells combined with dual drug nanoassemblies on ventricular remodeling and cardiac function after acute myocardial infarction in rats.Methods:A dual drug nano assembly of angiotensin 1-7 (SAAl-7) peptide and temisal was constructed. Male SD-rats (100 cases) were randomly divided into the sham group, model group, nano group, stem cell group, and combination group. And each group had 20 cases. Acute myocardial infarction rat models were established with anterior descending artery ligation in the model group, nano group, stem cell group, and combination group. The rats in the sham group took the same surgical steps but did not ligate the ligation line. In addition, rats in the stem cell group and combination group were injected with 20 μl of stem cells at the edge of the infarct area after ligation during the surgery. Rats in the other groups were injected with equal doses of phosphate buffered solution (PBS) by the same method. Starting from the day of surgical modeling, rats in nano group and combined group were injected with 0.5 ml of two-drug nano assemblies in the tail vein, while rats in the sham group, model group, stem cell group received a tail vein injection of an equal volume of 0.9% sodium chloride solution. After surgery, rats in all groups were continuously observed for 14 days. The cardiac function indicators, ventricular remodeling indicators, serum indicators, the myocardial infarction area, and the myocardial cell apoptosis rate of rats in all groups were detected and compared. The cardiac function indicators include left ventricular ejection fraction (LVEF), fraction shorting (FS), left ventricular end diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD). The ventricular remodeling indicators include left ventricle weight (LVW), left ventricular mass index (LVWI), and transdiameter of cardiomyocytes (TDM). The serum indicators include interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione, malondialdehyde, creatinine, and alanine aminotransferase (ALT).Results:Compared with the sham group, LVEF, FS, body mass, SOD, and glutathione levels in the model group were decreased (all P < 0.05), while LVEDD, LVESD, LVW, LVWI, TDM, IL-6, TNF-α, malondialdehyde, creatinine, ALT, myocardial infarction area, and myocardial cell apoptosis rate were increased (all P < 0.05). Compared with the model group, LVEF, FS, body mass, SOD, and glutathione levels in the nano group, stem cell group, and combination group were increased (all P < 0.05), while LVEDD, LVESD, LVW, LVWI, TDM, IL-6, TNF-α, malondialdehyde, creatinine, ALT, myocardial infarction area, and myocardial cell apoptosis rate were decreased (all P < 0.05). Compared with the nano group and stem cell group, LVEF, FS, body mass, SOD, and glutathione levels in the combination group were increased (all P < 0.05), while LVEDD, LVESD, LVW, LVWI, TDM, IL-6, TNF-α, malondialdehyde, creatinine, ALT, myocardial infarction area, and myocardial cell apoptosis rate were decreased (all P < 0.05). Conclusions:The combination of stem cells and dual drug nano assemblies can effectively treat acute myocardial infarction rats, improve their cardiac function, and reduce ventricular remodeling, which may be related to the reducing inflammatory response and oxidative stress inhibiting myocardial cell apoptosis and narrowing the area of myocardial infarction.

Today, medication remains a fundamental guarantee of long-term improvement in the quality of life for patients with Parkinson′s disease (PD). Since the 1960s, compound levodopa has been used to treat PD, and has been proved to be the most effective drug for the treatment of PD, which can not only improve the motor symptoms of PD patients, but also improve the quality of life. However, there are still some misunderstandings about the use of compound levodopa in clinical practice. With the progression of the disease, the related motor complications caused by its treatment have caused certain troubles to both clinicians and patients. This paper reviewed the results of related clinical studies at home and abroad, as well as guidelines and consensus, and carried out a comprehensive and systematic analysis and summary of the pharmacological characteristics of compound levodopa, evidence-based research evidence, clinical standard use, etc, combined with China′s national conditions and clinical practice, hoping to standardize the reasonable clinical application of compound levodopa and provide drug reference for the majority of clinical workers.

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.

Objective:To explore the correlation between transcranial sonography (TCS) combined with serum homocysteine (Hcy), blood glucose, blood lipids, the cognitive status of Parkinson′s disease (PD) patients, and to analyze the clinical application value of these parameters in assessing the cognitive status of PD patients.Methods:A total of 152 PD patients admitted to the Second Affiliated Hospital of Soochow University from January 2020 to June 2023 were retrospectively collected as the PD group, and 101 healthy examinees matched for age and gender during the same period were selected as control group. Clinical data [age, gender, duration of illness, Montreal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, Unified Parkinson′s Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) score, Hoehn-Yahr (H-Y) stage, etc.], serum tests (Hcy, blood glucose, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein concentration), and TCS examination results (third ventricular width, midbrain area, peak systolic velocity of bilateral middle cerebral arteries, bilateral middle cerebral artery resistance index, bilateral substantia nigra hyperechoic area) were collected. The two groups were divided into pure PD group and PD group with elevated Hcy, pure control group and control group with elevated Hcy, based on an Hcy concentration threshold of ≥15 μmol/L. The differences in the above parameters among the four groups were compared. The correlation between Hcy and cognitive status (MoCA score, MMSE score) of PD patients and the above parameters were analyzed.Results:The MoCA score and MMSE score of the PD group with elevated Hcy were lower than those of the pure PD group, and the UPDRS-Ⅲ score and H-Y stage were higher than those of the pure PD group (all P<0.001). The order of Hcy concentration from high to low was PD group with elevated Hcy, pure Hcy elevation group, pure PD group, and pure control group. The differences in serum data and TCS data among the four groups were statistically significant (all P<0.001). Spearman correlation analysis showed: ①In the PD group, the concentration of Hcy was positively correlated with glucose concentration, H-Y stage, low-density lipoprotein concentration, right middle cerebral artery resistance index, UPDRS-Ⅲ score, total cholesterol concentration, triglyceride concentration, left middle cerebral artery resistance index, third ventricular width, and age ( rs=0.422, 0.350, 0.348, 0.334, 0.325, 0.300, 0.293, 0.283, 0.221, 0.164, all P<0.05); Hcy concentration was negatively correlated with midbrain area, MMSE score, MoCA score, peak systolic velocity of right middle cerebral artery, peak systolic velocity of left middle cerebral artery, and high-density lipoprotein concentration ( rs=-0.328, -0.282, -0.245, -0.229, -0.224, -0.192, all P<0.05). ②Clinical data, serum data, and TCS data of PD patients were all correlated with MoCA score and MMSE score, with midbrain area showing the largest positive correlation ( rs=0.524, 0.516; both P<0.05) and H-Y stage showing the largest negative correlation( rs=-0.490, -0.468; both P<0.05). Conclusions:PD patients with elevated Hcy have lower cognitive scores than pure PD patients. The correlation between Hcy concentration and blood glucose concentration is the highest in PD patients, followed by H-Y stage. The cognitive scores of PD patients are most correlated with midbrain area and unrelated to substantia nigra hyperechoic area. Lowering serum Hcy concentration in PD patients may be one of the ways to delay cognitive impairment.

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.