Objective To optimize the process conditions and analyze the components of alkaloids from Zanthoxylum bungeanum Maxim（Z. bungeanum）using macroporous resin. Methods Combining single factor tests and orthogonal tests, the content of hydroxy-α-sanshool（HAS）and hydroxy-β-sanshool（HBS）were considered as indexes to determine the best process parameters. Ultra-performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E）was used to identify the structures of alkaloids. Results The optimal conditions were Mitsubishi HP-20 macroporous resin, the loading solution concentration was 0.2 g crude drug/ml, the ratio of crude drug to resin volume was 1 g∶2.5 ml, the diameter/height ratio of resin column was 1∶7, the dynamic adsorption flow rate was 4 times of bed volume（BV）per hour, and the adsorption time was 1 h. Impurities were removed by using 2 BV of 20% ethanol, 5 BV of 80% ethanol was used to elution, and the content of HAS and HBS was 4.71% and 1.02%, respectively. A total of 20 alkaloids were identified from Z. bungeanum. Conclusion This method was stable and feasible, obtaining high purity and various kinds of alkaloids, which could be used for the enrichment and purification of alkaloids from Z. bungeanum.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To construct a diagnostic model based on the information of the TCM four diagnoses in hyperactive liver yang syndrome in patients with essential hypertension.Methods Syndromic investigation was carried out in patients with essential hypertension in some hospitals in Fujian and Beijing,and diagnostic information such as age,gender,symptoms,tongue and pulse were collected.On the basis of statistical analysis,this study adopted C5.0,CRT,CHAID and QUEST decision tree models respectively.After evaluating the stability and performance consistency of the models,the accuracy of the models was measured by diagnostic rate,and the optimal model of hyperactivity of liver yang in essential hypertension was selected.Results Totally 533 patients with essential hypertension were included,including 198 patients with hyperactive liver yang syndrome and 335 patients without hyperactive liver yang syndrome.The diagnostic rates of the four models were 75.2%,66.2%,67.7%and 65.0%,respectively.The diagnostic efficiency of C5.0 was better than that of CRT,CHAID and QUEST models."Aggravation after emotional excitement,poor complexion,string-like pulse,irritability,head swelling pain,bitter mouth,heavy pulse,fatigue,dark tongue,irritability,dizziness,thin pulse,yellow fur"could be regarded as the specific items of the syndrome model of hyperactive liver yang in essential hypertension.Conclusion The C5.0 decision tree model can clearly and intuitively identify the hyperactive liver yang syndrome in essential hypertension patients based on clinical TCM four diagnostic information data,and summarize diagnostic rules.

Aim To observe the inhibitory effect of Alpha-momorcharin (α-MMC) on the inflammatory cytokine storm of Ml-type inflammatory macrophages induced by LPS and explore its possible targeting mechanism. Methods Western blot was used to detect the expression of WIL2-S B lymphocytes, H9 T lymphocytes, THP-1 monocytes and M0 macrophages LRP1 receptor protein. CCK-8 method was used to detect the survival rate of the four cells. ELISA was used to detect the expression level of inflammatory cytokines in Ml macrophages. Western blot was used to detect the expression of TLR4 signaling pathway-related protein in Ml macrophages. Results Macrophages had a high density of LRP1 receptors consistent with monocytes; the survival rate of α-MMC on the four cells was positively correlated with the density of this receptor; α-MMC inhibited the expression of inflammatory cytokinesTNF-α, IL-lβ, IL-6, IL-8, MlP-lα and MCP-1 in Ml macrophages in a dose-and time-dependent manner; α-MMC showed significant inhibition to TAKl/pTAK1, p-JNK, p-APl and p-p65 signaling proteins of the TLR4 signaling pathway, and this inhibition could be blocked by the LRP1 receptor blocker RAP. Conclusions α-MMC selectively inhibits macrophage inflammatory cytokine synthesis by inhibiting TAK1 of the TLR4 signaling pathway, which in turn inhibits the downstream NF-ΚB and MAPK pathways, mediated by the LRP1 receptor. The selective immunosuppressive effect of α-MMC on macrophages may make it a very promising agent for the treatment of acute infectious macrophage activation syndrome (MAS).

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Oral mucosal drug delivery has the advantages of rapid drug absorption, no first-pass effect and good patient compliance. However, factors such as low drug dissolution, saliva carrying the drug into the gastrointestinal tract and the existence of physiological barriers in the mucosa may affect the mucosal permeation and bioavailability of the drug. Nanotechnology applied to drug oral mucosa delivery can overcome the above disadvantages and obtain efficient absorption effect. This paper describes the physiological structure of oral mucosa and the factors affecting the absorption of drugs in oral mucosa, reviews the application of nanotechnology such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, polymer nanoparticles, polymer micelles and nanohybrid suspensions in oral mucosal drug delivery and the mechanism of promoting drug absorption, summarizes the main problems of current research, and gives an outlook on the application of nano oral mucosal drug delivery system. The main problems of current research are summarized, and the prospects for the application of nano oral mucosal drug delivery systems are discussed.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Objective:To use the spatiotemporal distribution model and INLA algorithm to study the spatiotemporal characteristics and influencing factors of tuberculosis in Shanghai and to provide a theoretical basis for formulating regional tuberculosis epidemic prevention and control measures.Methods:Based on the data of registered pulmonary tuberculosis cases in Shanghai during 2013-2020 derived from the tuberculosis management information system of China Disease Control and Prevention Information System, the hierarchical Bayesian model was adopted to fit the tuberculosis case data, identify the spatiotemporal variation characteristics of tuberculosis, and explore the potential socioeconomic characteristics and other factors related to health services and spatiotemporal characteristics.Results:From 2013 to 2020, 29 281 registered tuberculosis cases were reported in Shanghai, with an average annual incidence of 25.224/100 000. From 2013 to 2020, the incidence trend increased first and then decreased, the highest incidence was reported in 2014 (27.991/100 000). The incidence of tuberculosis in Shanghai is characterized by spatial clustering. Through the spatial characteristics and risk analysis of the reported incidence of tuberculosis, it is found that the high-risk area of tuberculosis in Shanghai is the suburban communities, whereas downtown communities are the low-risk areas. The incidence risk of pulmonary tuberculosis is associated with the gross domestic product per capita ( RR=0.48), the number of beds per 10 000 persons ( RR=0.56), the normalized vegetation index ( RR=0.50), and the night light index ( RR=0.80). Conclusions:With the steady progress of tuberculosis prevention and control in the central urban area of Shanghai, special attention should be paid to the prevention and control in the suburbs further to improve the social and economic level in the suburbs and increase the coverage rate of urban green space, to reduce the incidence of tuberculosis and reduce the disease burden of tuberculosis in Shanghai.

Objective:To investigate the prognosis of robotic pancreatoduodenectomy after the learning curve and open pancreatoduodenectomy for pancreatic cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 396 patients who underwent curative pancreatoduodenectomy for pancreatic duct adenocar-cinoma in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from January 2017 to December 2018 were collected. There were 244 males and 152 females, aged 64(range, 36?92)years. Of 396 patients, 86 cases undergoing robotic pancreatoduodenectomy were divided into robotic group, 310 cases undergoing open pancreatoduodenectomy were divided into open group. Observa-tion indicators: (1) propensity score matching and comparison of general data between the two groups after matching; (2) follow-up and survival analysis. Follow-up was conducted by telephone interview or outpatient examinations including tumor markers and abdominal imaging examina-tions to detect survival of patients up to March 2022. Overall survival was defined as the time from the surgery date to death or the last follow-up. Disease-free survival was defined as the time from the surgery date to tumor recurrence or the last follow-up. The propensity score matching was conducted by 1∶1 matching using the nearest neighbor method. Normality of measurement data was examined using the Shapiro-Wilk test. Measurement data with skewed distribution were described as M(range), and comparison between groups was analyzed using the Mann-Whitney rank-sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used for survival analysis. An intent-to-treat analysis was performed in this study, patients who were converted to laparotomy from robotic surgery were still divided into the robotic group. Results:(1) Propensity score matching and comparison of general data between the two groups after matching: 164 of 396 patients had successful matching, including 82 cases in robotic group and open group, respectively. Before propensity score matching, the body mass index, cases in stage T1, T2, T3, T4, cases in N0, N1, N2 were 23.4(range, 21.4?25.3)kg/m 2,24, 41, 10, 11, 52, 27, 7 for the robotic group, versus 22.4(range,20.3?23.9)kg/m 2,57, 144, 22, 87, 131, 132, 47 for the open group, showing significant differences in the above indicators between the two groups ( Z=3.01, 2.63, 3.03, P<0.05). After propensity score matching, cases of males, age, body mass index, cases with American Society of Anesthesiologists (ASA) score as 1, 2, 3, CA19-9, cases with preoperative biliary drainage, cases with portal vein resection, cases with pancreatic resection margin <1 mm, cases in stage T1, T2, T3, T4, cases in stage N0, N1, N2, cases with nerve invasion, cases with tumor differentiation as high-medium differentiation, medium-low differentiation, low differentiation, cases with adjuvant chemotherapy were 51, 65(range, 59?69)years, 23.0(range, 21.0?25.2)kg/m 2, 32, 41, 9, 160.4(range, 46.7?377.2)U/mL, 21, 9, 8, 21, 40, 10, 11, 48, 27, 7, 76, 26, 47, 9, 53 for the robotic group, versus 58, 65(range, 58?69)years, 23.3(range, 21.4?25.3)kg/m 2, 35, 39, 8, 172.0(range, 69.7?402.9)U/mL, 26, 9, 10, 24, 40, 7, 11, 49, 28, 5, 76, 22, 49, 11, 57 for the open group, showing no significant difference in the above indicators between the two groups ( χ2=1.34, Z=0.18, 0.34, 0.49, 0.51, χ2=0.75, 0.00,0.25, Z=0.59, 0.27, χ2=0.00, Z=0.76, χ2=0.44, P>0.05). (2) Follow-up and survival analysis: after propensity score matching, 164 patients were followed up for 54(range, 1?67)months. The follow-up time of patients was 55(range, 51?59)months for the robotic group, versus 54(range, 50?58)months for the open group, respectively, showing no significant difference between the two groups ( Z=0.48, P>0.05). During the follow-up, the 1-year overall survival rate, 3-year overall survival rate, the median survival time, 1-year disease-free survival rate, 3-year disease-free survival rate, the median disease-free survival time, tumor recurrence rate, cases with recurrence pattern as local recurrence, liver recurrence, other distant recurrence, local and distant recurrence were 81.7%, 39.0%, 27 months(95% confidence interval as 19?33 months), 61.0%, 34.2%, 15 months(95% confidence interval as 12?18 months), 54.9%(45/82), 12, 16, 9, 8 for the robotic group. The above indicators were 79.3%, 36.0%, 24 months(95% confidence interval as 19?31 months), 59.8%, 27.5%, 15 months(95% confidence interval as 10?20 months), 58.5% (48/82), 10, 22, 6, 10 for the open group. There was no significant difference in overall survival or disease-free survival between the two groups ( χ2=0.39, 0.47, P>0.05). There was no significant difference in tumor recurrence rate or tumor recurrence site between the two groups either ( χ2=0.22, 1.86, P>0.05). Conclusion:After the learning curve, robotic pancreato-duodenectomy has non-inferior prognosis compared with open pancreatoduodenectomy.

ObjectiveTo reveal the mechanism of action of Huangqi Guizhi Wuwutang in the treatment of rheumatoid arthritis by pharmacological research based on its clinical application. MethodThe collagen-induced arthritis （CIA） rat model was established by injecting bovine type Ⅱ collagen and Freund's adjuvant at the tail， and was treated with different concentrations of Huangqi Guizhi Wuwutang. The rats were randomly divided into blank group， model group， methotrexate （0.9 mg·kg^-1） group， and Huangqi Guizhi Wuwutang low- and high-dose （5.13， 20.52 g·kg^-1·d^-1） groups， with continuous intragastric administration for 4 weeks. The degree of joint swelling， weight， degree of foot swelling and arthritis index score were determined and the pathological changes of ankle joints were detected by hematoxylin and eosin （HE） staining to observe the therapeutic effect of Huangqi Guizhi Wuwutang on rheumatoid arthritis. In addition， enzyme-linked immunosorbent assay （ELISA） and Western blot were used to measure the expression of interleukin 1β （IL-1β）， interleukin 6 （IL-6）， interleukin 10 （IL-10） and tumor necrosis factor-α （TNF-α） in serum and the expression of nuclear factor kappa-B （NF-κB） pathway related proteins in synovial tissue， respectively to clarify the molecular mechanism of Huangqi Guizhi Wuwutang in the treatment of rheumatoid arthritis. ResultCompared with the conditions in blank group， the body weight and IL-10 level were decreased （P<0.01）， and the degree of foot swelling and arthritis index score， the levels of IL-1β， IL-6 and TNF-α， and the expression of NF-κB pathway related proteins were increased （P<0.01，） in the model group， with impaired morphology and function of the ankle joint. Additionally， compared with the model group， Huangqi Guizhi Wuwutang low- and high-dose groups had increased body weight of rats and IL-10 level （P<0.01）， and reduced degree of foot swelling and arthritis index score （P<0.05， P<0.01）， levels of IL-1β， IL-6 and TNF-α （P<0.01） and expression of NF-κB pathway related proteins （P<0.05， P<0.01）， with improved function and morphology of the ankle joint. ConclusionHuangqi Guizhi Wuwutang can significantly alleviate joint inflammatory injury by down-regulating NF-κB pathway and reducing the inflammatory response in CIA rats.