OBJECTIVE To investigate the potential mechanism by which Juanxiao decoction improves bronchial asthma （hereinafter referred to as “asthma”） based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome signaling pathway. METHODS Female SD rats were randomly assigned to normal group， model group and Juanxiao decoction low-， medium- and high-dose groups （0.36， 0.72 and 1.44 g/kg， calculated based on crude drug weight）， as well as positive control group （Dexamethasone acetate tablets， 0.2 mg/kg）， with 10 rats in each group. Except for the normal group， asthma models were established in the remaining groups via intraperitoneal injection of ovalbumin combined with aluminum hydroxide， followed by nebulized inhalation of ovalbumin. On day 14 of the experiment， rats in each group received intragastric administration of the corresponding solution or normal saline， once a day， for 7 consecutive days. Following the final administration， the following parameters were measured in each group： lung function indexes （forced vital capacity， forced expiratory volume in 0.3 second， peak expiratory flow）， serum levels of inflammatory markers （interleukin-1β， interleukin- 18）， and the percentages of inflammatory cells （lymphocytes， eosinophils， neutrophils） in bronchoalveolar lavage fluid. Histopathological changes in lung tissue were observed， and the protein and mRNA expressions of nuclear factor-kappa B （NF- κB）， NLRP3 and caspase-1 in lung tissue were detected. RESULTS Compared with the normal group， pathological changes such as alveolar wall thickening and inflammatory cell infiltration were observed in rats in the model group. All pulmonary function indicators were significantly reduced in rats in the model group and the administration groups. The levels of inflammatory markers， the percentages of inflammatory cells， and the protein and mRNA expressions of NF-κB， NLRP3 and caspase-1 were significantly elevated or up-regulated （P＜0.05）. Compared with the model group， pathological changes in rats in each dosage group of Juanxiao decoction were significantly alleviated， and all quantitative indicators showed dose-dependent improvements （P＜0.05）. CONCLUSIONS Juanxiao decoction can reduce airway inflammatory responses in asthmatic rats， alleviate lung function impairment， and improve pathological changes such as inflammatory cell infiltration. Those effects may be related to the inhibition of the NLRP3 inflammasome signaling pathway.

ObjectiveTo investigate the effect and mechanism of Yiqi Wenyang Huwei decoction （YWHD） on airway inflammation in bronchial asthma （BA） rats based on transforming growth factor-β₁ （TGF-β₁）/SMAD family member 3 （Smad3） signaling pathway. MethodSixty male SD rats were randomly divided into a normal group， a model group， a dexamethasone （DEX） group， and low-， medium-， and high-dose YWHD groups， with 10 rats in each group. The BA model was induced by intraperitoneal injection of 1 mL of ovalbumin （OVA）-aluminum hydroxide suspension for sensitization， followed by nebulization with 2% OVA. One hour before daily OVA nebulization， the control group was treated with saline， the DEX group with DEX solution at 0.2 g·L^-1， and the low-， medium-， and high-dose YWHD groups with YWHD at 1， 2， 4 g·mL^-1， respectively. General conditions and lung function were observed. Bronchoalveolar lavage fluid （BALF） and serum were collected to count inflammatory cells in BALF and measure immunoglobulin E （IgE） levels in serum and inflammatory cytokines in BALF using enzyme-linked immunosorbent assay （ELISA）. Pathological changes in lung tissues， collagen deposition， and airway mucus secretion were observed by hematoxylin-eosin （HE）， Masson， and periodic acid-Schiff （PAS） staining. TGF-β₁/Smad3-related mRNA and protein levels in lung tissues were determined by Real-time fluorescent quantitative polymerase chain translation （Real-time PCR） and Western blot analysis. ResultCompared with the normal group， the model group showed increased total airway resistance （RL） and decreased dynamic compliance （Cdyn） （P<0.05， P<0.01）， elevated serum IgE levels， increased inflammatory cell counts， and higher inflammatory cytokine levels in BALF （P<0.01）. Additionally， there was significant inflammatory cell infiltration， collagen deposition， and mucus secretion in lung tissues. The levels of TGF-β₁， α-smooth muscle actin （α-SMA）， and Smad3 phosphorylation in lung tissues were significantly increased （P<0.01）. Compared with the model group， the DEX group and high-dose YWHD group exhibited significantly reduced RL （P<0.01）， improved lung dynamic compliance （P<0.05）， and lower serum IgE levels， inflammatory cell counts， and inflammatory cytokine levels in BALF （P<0.05）. Moreover， these treatments alleviated pathological damage in lung tissues and reduced the levels of TGF-β₁， α-SMA， and Smad3 phosphorylation （P<0.01）. ConclusionYWHD reduces airway inflammation， improves pathological damage， and mitigates airway remodeling in bronchial asthma rats， possibly by downregulating TGF-β₁， α-SMA protein levels， and Smad3 phosphorylation.

Objective:To evaluate the reliability and validity of a questionnaire assessing the leadership qualities of primary healthcare institution managers, and to further clarify the current state of leadership development among management teams of community health service centers in Shanghai.Methods:The study was a cross-sectional survey. It was conducted from August to December 2021, and used a stratified sampling method. Using a self-developed questionnaire for primary healthcare institution managers, we surveyed 279 individuals from 10 community health service centers in Shanghai, including management teams, middle-level cadres, general practitioners, and staff from health administrative departments in their respective districts. Leadership qualities were evaluated on five dimensions: inspiration, decisiveness, control, influence, and foresight. Cronbach′s α coefficient and split half coefficient were used to analyze the reliability of the questionnaire, and confirmatory factor analysis was used to assess the structural validity of the scale.Results:The overall Cronbach′s α reliability of the questionnaire for the comprehensive management of community health service centers was 0.96, and the Spearman-Brown split-half coefficient was 0.94. The validity analysis yielded a KMO value of 0.975, the RMSEA for factor analysis was 0.085, and the adaptation indexes all met the model adaptation conditions. Of the 279 participants, 174 were female (62.4%), 257 held a mid-level or higher professional title (92.1%). The overall leadership score of the community health service center management teams was (4.43±0.59), with the dimensions ranked from highest to lowest as follows: inspiration (4.52±0.55), decisiveness (4.46±0.62), control (4.44±0.60), influence (4.42±0.63), and foresight (4.32±0.69). The foresight score was significantly lower than the other four dimensions (all P<0.05). Conclusions:The questionnaire used to assess the leadership qualities of primary healthcare institution managers is reliable and valid. The development of leadership qualities among management teams of community health service centers in Shanghai is unbalanced, with foresight being the weakest dimension.

ObjectiveTo observe the regulatory effects of Yiqi Wenyang Huwei decoction （YWHD） on autophagy and phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt）/mammalian target of rapamycin （mTOR） signaling pathway in asthmatic rats and bronchial epithelial cells （16HBE） and further reveal the mechanism of YWHD in treating bronchial asthma （BA）. MethodForty-eight rats were randomly assigned into normal group， model group， dexamethasone group， and low-， medium-， and high-dose YWHD groups， with 8 rats in each group. The rat model of BA was established by intraperitoneal injection with ovalbumin （OVA） + aluminum hydroxide suspension and atomizing inhalation with OVA for 2 weeks. The normal group was administrated with an equal dose of normal saline. The bronchial maximum airway resistance （Max Rrs） induced by methacholine chloride （Mch） was determined by an animal lung function evaluation system. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin （IL）-4， IL-13， IL-6， IL-33， IL-25， tumor necrosis factor-α （TNF-α）， and immunoglobulin E （IgE） in the bronchial alveolar lavage fluid. Hematoxylin-eosin （HE） and Masson staining were used for observation of the pathological changes of bronchi in the lung tissue. The immunofluorescence assay was employed to measure the levels of the autophagy-associated proteins LC3B and Beclin1. The IL-13-induced autophagy of 16HBE cells exposed to the YWHD-containing serum was observed， and the autophagy level was traced by mRFP-GFP-LC3 adenovirus infection. The protein levels of LC3Ⅱ/Ⅰ， p-PI3K， p-Akt and p-mTOR were determined by Western blot. ResultCompared with the normal group， the model group showed increased Max Rrs （P<0.01） and elevated levels of IL-4， IL-13， IL-6， IL-33， IL-25， TNF-α， and IgE in the bronchial alveolar lavage fluid （P<0.05，P<0.01）. The modeling caused focal infiltration of inflammatory cells and lymphocytes around bronchus and blood vessels， epithelial goblet cell metaplasia， and increased subepithelial collagen deposition. Furthermore， it up-regulated the protein levels of LC3B and Beclin1 （P<0.01）， promoted the autophagy flux of GFP to mRFP in 16HBE cells induced by IL-13， down-regulated the protein levels of p-PI3K， p-Akt， and p-mTOR， and increased the LC3Ⅱ/Ⅰ ratio （P<0.01）. Compared with the model group， medium- and high-dose YWHD decreased Max Rrs （P<0.01）， lowered the levels of IL-4， IL-13， IL-6， IL-33， IL-25， TNF-α， and IgE in the bronchial alveolar lavage fluid （P<0.05， P<0.01）， and reduced lymphocyte and granulocyte infiltration in bronchi of the lung tissue， epithelial goblet cell metaplasia， and subepithelial collagen deposition. Moreover， they down-regulated the protein levels of LC3B and Beclin1 （P<0.05， P<0.01）， decreased the autophagy flux of GFP to mRFP， up-regulated the protein levels of p-PI3K， p-Ak， and p-mTOR， and decreased the LC3Ⅱ/Ⅰ ratio （P<0.05， P<0.01）. ConclusionYWHD ameliorates airway hyperresponsiveness and airway inflammation and inhibits the autophagy of airway epithelial cells in the lung tissue of BA rats by activating the PI3K/Akt/mTOR signaling pathway.

Objective:To analyze the trend and hot spots of research on multimorbidity.Methods:The Chinese and English literature in databases of CNKI, Wanfang data and Web of science from inception to July 2022 were retrieved using "multimorbidity" and "multiple chronic conditions" as the search terms. The scientific knowledge mapping software VOSviewer was used to analyze the co-occurrence network of scientific knowledge from the aspects of countries, Chinese and English keywords,burst terms and existing research results; and the status quo and hot trends of studies on multimorbidity at home and abroad were summarized and compared.Results:A total of 251 Chinese publications and 6 351 English publications were included. From the perspective of research trends, the overall trend of domestic and international publications showed a fluctuating upward trend in general, but the pace of development was different. The cooperation network represented by the United States, England, Canada, China, Japan, Australia and other countries was the largest regional cooperation network. Germany, the Netherlands, the United States, Australia and other countries were the first regions to carry out studies on multimorbidity. Studies on multimorbidity in China mainly focused on three topics: diagnosis, treatment and care of multimorbidity, common disease management of multimorbidity, and research methods of multimorbidity. The English literature mainly focused on the clustering of three topics: multi-disease co-diagnosis and care research, multi-disease co-management model research, and multimorbidity related research. The analysis of burst terms indicated the research focus and trend change in different time periods. The results of the outburst word analysis showed that the recent research hotspots of multimorbidity were public health, machine learning, geriatric medicine and so on.Conclusions:The number of studies on the multimorbidity is rapidly increasing both domestically and internationally, and related research in China is still in the early stages of development. In terms of research hotspots, the research of multimorbidity has gradually shifted from phenomenon description to topics such as medical services and research methods of multimorbidity.

Cryptococcal meningitis is a common and refractory central nervous system infection,with high rates of mortality and disability.The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion.Based on the current situation of cryptococcal meningitis in China,the management of cryptococcal meningitis includes 6 aspects:introduction,microorganism identification,clinical manifestations and diagnosis,principles of antifungal therapy,treatment of refractory and recurrent meningitis,treatment of intracranial hypertension.There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis.This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines.The importance of early diagnosis,combined long-term antifungal therapy,control of intracranial hypertension are emphasized.

OBJECTIVETo investigate the role of miR-144-3p in regulating osteogenic differentiation of bone marrow mesenchymal stem cells and predict its target genes.

METHODSRat bone marrow mesenchymal stem cells (BMSCs) with induced osteogenic differentiation were examined for the expressions of Runx2, OCN and miR-144-3p. The effects of transfection with a miR-144-3p mimic or a miR-144-3p inhibitor were tested on the osteogenic differentiation of the BMSCs. The changes in the expressions of the predicted target of miR-144-3p in the BMSCs during induced osteogenic differentiation were examined using Western blotting and qRT-PCR.

RESULTSRat BMSCs with induced differentiation into osteoblasts exhibited a progressive increase in the expressions of Runx2 and OCN (two markers of osteogenic differentiation), while the expression of miR-144-3p gradually decreased during the differentiation till reaching the lowest level at 21 days of induction. In rat BMSCs, transfection with the miR-144-3p mimic significantly decreased ALP activity ( < 0.05) wile transfection with the miR-144-3p inhibitor significantly increased ALP activity ( < 0.05) in rat BMSCs. Analysis based on miRanda, microRNA.org database and TargetScan suggested that Smad4 was the most likely target gene of miR-144-3p. The results of qRT-PCR showed no significant differences in expression levels of Smad4 among the cells with different treatments ( > 0.05), while Western blotting revealed a significantly decreased expression of Smad4 in the cells transfected with miR-144-3p mimics and an increased Smad4 expression in the cells transfected with the miR-144-3p inhibitor as compared with the control cells ( < 0.05).

CONCLUSIONSmiR-144-3p participates in the regulation of osteogenic differentiation of rat BMSCs, and its inhibitory effect on osteogenic differentiation is achieved probably by decreasing the expression level of Smad4.

Objective: To compare the efifcacy and safety of rivaroxaban and warfarin on thrombolytic disease prevention in very elderly patients. Methods: A total of 90 patients with high risk of venous thrombosis treated in our hospital from 2012-03 to 2014-03 were enrolled. The patients' mean age was (82.4±5.5) years and randomized into 2 groups: Rivaroxaban group, patients received oral rivaroxaban 10 mg/day,n=44 including 34 male and 10 female; Warfarin group, patients received oral warfarin, INR was monitored and kept at stable level of 1.6-2.5,n=46 including 38 male and 8 female. All patients were followed-up for 12 months. Hemoglobin and platelet levels, coagulation, liver and kidney functions, end point events were monitored before and 1, 3, 6, 12 months after treatment. Major efficacy endpoints included all-cause death, recurrent or new onset of venous thrombosis, pulmonary embolism, cerebral and cardiovascular events; major safety endpoints included massive hemorrhages, clinically relevant bleeding and worsening of liver, kidney functions. Results: No patient died during follow-up period. The average INRs in Warfarin group were (2.02±0.46), (1.98±0.54), (2.03±0.56) and (2.04±0.46) at 1, 3, 6 and 12 months of treatment. Efficacy and safety were similar between 2 groups, Warfarin group had 7 patients with massive hemorrhages at 12 months of treatment and it was 2 patients more than that in Rivaroxaban group which had no statistic meaning. Hemoglobin and platelet levels, coagulation, liver and kidney functions were similar between 2 groups.Conclusion: Oral rivaroxaban was effective for preventing thromboembolic disease in very elderly patients, 10 mg/day was a safe dose; efifcacy of rivaroxaban was similar to warfarin while it was easier to use and with better compliance.

Mini health technology assessment (Mini-HTA) was developed from traditional HTA,based on the hospital needs.It is a very important decision making method and reference tool for the hospital policy makers.Currently there is no report of using Mini-HTA ease on introducing new equipment in China.Present paper introduces the Mini-HTA to provide reference for others hospitals in China.

Objective To summarize the common causes and types of circuit failure after vagus nerve stimulator (VNS) implantation,and analyze the available methods of resolving these problems.Methods Three patients with postoperative circuit fault in the 97 patients performed VNS implantation for drug refractory epilepsy in our hospital from October 2011 to January 2014,and three patients with postoperative circuit fault performed surgery in other hospitals at the same period were chosen in this study.The causes of circuit failure of these 6 patients were identified by performing system diagnostics and X-ray evaluation.A revision surgery may be necessary if a broken or damaged lead was suspected.Results In these 6 patients of device failure,two patients were due to the disconnection of the lead from the pulse generator;the lead impedance became normal after re-inserting the existing lead connector pins into the pulse generator following proper lead insertion techniques.Four patients performed lead revision surgery to replace or remove the existing lead;in 3 of them,the helices and associated scar tissues were removed from the vagus nerve under the microscope,and a new set of electrodes was placed;in one of them,the lead was transected as much as possible and the distal portion of the lead was severed at the neck following the removal of pulse generator.There were no complications such as hoarse voice,dyspnea,slow rhythm,subcutaneous hematoma or infection after the revision surgery.Five patients were followed up,indicating the devices work normally.Four patients had obvious improvement,and one patient had no significant improvement after the revision surgery.Conclusions The high lead impedance is the main manifestation of circuit failure after vagus nerve stimulator implantation.Surgical exploration is an effective method to identify and resolve these problems.