Mechanical ventilation(MV)provides life support for critically ill respiratory patients,but in the meantime can cause fatal ventilator-induced lung injury(VILI),and the latter remains a major challenge in respiratory and critical care medicine,because the pathological mechanism has not been fully elucidated.Recent studies show that on the one hand,in the lung with VILI,there exists airway collapse at multi-sites of an individual airway,which can not be explained by traditional airway collapse models.But on the other hand,under MV conditions,airway smooth muscle cells(ASMC)exhibit abnormal mechanical behaviors,accompanied by regulation of Piezo1 expression and endoplasmic reticulum stress.These phenomenons indicate that the MV-induced abnormal mechanical behavior of ASMC is closely related to multiple airway collapse and VILI.Therefore,by studying the MV-induced changes of ASMC mechanical behaviors and their relationship with airway collapse in lung injury,as well as the related mechanochemical signal coupling process,it is expected to reveal a novel mechanism of MV-associated airway collapse and lung injury from the perspective of cell mechanics.In this review,the recent research progress of airway collapse during MV,the regulation of ASMC mechanical behavior by MV-related high stretch,especially the related mechanochemical signal coupling mechanism is summarized.These advances may provide a novel insight for exploring the roles of ASMC abnormal mechanical behavior in the pathological mechanism of VILI,alternative targets of drug intervention for prevention and treatment of VILI,as well as for optimizing the ventilation mode in clinical practice.

Objective The objective of this study was to establish a mouse model of allergic rhinoconjunctivitis and investigate the role of the NLRP3 signaling pathway in allergic rhinoconjunctivitis.Methods Thirty-three female C57 mice(SPF)were randomLy divided into 3 groups:the control group,the experimental group,and the NLRP3-/-group.On days 0,4,7,14,and 21,the experimental group and NLRP3-/-group received a 0.2 mL intraperitoneal injection of medicine containing OVA(100 μg)and adjuvant Al(OH)3(4 mg),respectively.After an interval of 3 days,each eye and nose were dosed with 10 μL of 5%OVA for five consecutive days a week to induce allergic symptoms.During sensitization and excitation stages,the control group was replaced with an equiva-lent amount of PBS.Ocular and nasal symptoms were observed and scored.The levels of OVA-specific IgE,IL-4,IL-17,and IL-18 in serum were measured using ELISA,while changes in palpebral conjunctiva and nasal mucosa were assessed by hematoxylin-eosin staining.The expression of NLRP3 mRNA in conjunctival tissue and nasal mucosa was determined using real-time PCR analysis.Statistical analysis was performed using SPSS17.0 software with P<0.05 considered as statistically significant difference.Results The experimental group and NLRP3-/-group exhibited induced nasal and ocular allergic symptoms.In the experimental group,the duration of nasal allergy symptoms was(10.500±1.080)days,while the duration of eye allergy symptoms was(20.300±2.058)days.In the NLRP3-/-group,the duration of nasal allergy symptoms was(13.400±1.955)days,and for eye allergy symp-toms it was(20.900±2.132)days.The duration of nasal allergies in the NLRP3-/-group significantly exceeded that in the experimental group(P<0.05),whereas there were no significant differences observed in eye allergy durations between these two groups(P>0.05).Levels of OVA-specific IgE,IL-4,and IL-17 were significantly higher in both the experimental and NLRP3-/-groups compared to those in the control group(P<0.05).Additionally,serum IL-18 content increased significantly in the experimental group when compared with both control and NLRP3-/-groups(P<0.05).Conjunctival tissue lesions as well as nasal mucosa damage were evident in both experimental and NLRP3-/-groups.mRNA expression levels of NLRP3 within conjunctival tissue and nasal mucosa from the experimental group showed a significant increase when compared to those from both control and NLRP3-/-groups(P<0.05).Conclusion Allergic rhinoconjunctivitis pathogenesis is influenced by various factors;however,the involvement of NLPR3 signaling pathway promotes its development.

Post-traumatic stress disorder (PTSD) presents with complex and diverse clinical manifestations, making accurate and objective diagnosis challenging when relying solely on clinical assessments. Therefore, there is an urgent need to develop reliable and objective auxiliary diagnostic models to provide effective diagnosis for PTSD patients. Currently, the application of graph neural networks for representing PTSD is limited by the expressiveness of existing models, which does not yield optimal classification results. To address this, we proposed a multi-graph multi-kernel graph convolutional network (MK-GCN) model for classifying PTSD data. First, we constructed functional connectivity matrices at different scales for the same subjects using different atlases, followed by employing the k-nearest neighbors algorithm to build the graphs. Second, we introduced the MK-GCN methodology to enhance the feature extraction capability of brain structures at different scales for the same subjects. Finally, we classified the extracted features from multiple scales and utilized graph class activation mapping to identify the top 10 brain regions contributing to classification. Experimental results on seismic-induced PTSD data demonstrated that our model achieved an accuracy of 84.75%, a specificity of 84.02%, and an AUC of 85% in the classification task distinguishing between PTSD patients and non-affected subjects. The findings provide robust evidence for the auxiliary diagnosis of PTSD following earthquakes and hold promise for reliably identifying specific brain regions in other PTSD diagnostic contexts, offering valuable references for clinicians.
Humans ; Stress Disorders, Post-Traumatic/diagnostic imaging* ; Neural Networks, Computer ; Algorithms ; Brain/diagnostic imaging* ; Magnetic Resonance Imaging

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals ; Mice ; Male ; Cell Line ; Rats ; Kidney/physiology* ; Fibrosis/drug therapy* ; Renal Insufficiency, Chronic/drug therapy* ; Adenine ; Epithelial-Mesenchymal Transition ; Aquaporin 1/metabolism*

OBJECTIVE： To investigate the reasons for drug shortage in medical institutions of Sichuan province and put forward relevant countermeasures， and to provide reference for establishing supply security mechanism of drug shortage. METHODS： Questionnaire survey was conducted to investigate drug shortage in 78 medical institutions of the province during Jan. 2015-Jun. 2017. Traceability investigation was conducted from manufacturers and distribution enterprises involved in drug shortage. Questionnaire survey and field investigation were combined to analyze the reasons for drug shortage in Sichuan province and put forward countermeasures. RESULTS： Totally 78 questionnaires were sent out to medical institutions with recovery rate and effective rate of 100％. A total of 206 drugs were reported by 78 medical institutions， involving 240 specifications for shortage in total. Totally 140 questionnaires and 68 questionnaires were distributed to the manufacturers and distribution enterprises involved in drug shortage， and the recovery rate and effective rate were all 100％. Combined with the field survey， survey results of shortage drugs of 212 specifications were obtained. From the perspective of manufacturers， the most important factors causing drug shortage were the increase of production cost （66.51％） and circulation cost（26.88％）. From the perspective of distribution enterprises，the main factors causing drug shortage were insufficient supply of drugs（75.47％），inventory management（16.51％） and price inversion（11.32％）. CONCLUSIONS： Main reasons of drug shortage from manufacturers and distribution enterprises include the increase of production cost and circulation cost， drug price inversion， inventory management and bidding procurement. It is suggested that measures should be taken to improve the bidding and pricing system of drugs， mobilize the enthusiasm of enterprises； improve the early warning mechanism of drug shortage on the enterprises， strengthen information communication； establish the mechanism of drug shortage reserve， organize the emergency production of drug for shortage； strengthen the management of drug shortage supply chain， purify the unhealthy atmosphere in the market； improve the emergency disposal methods of drug shortage， and improve the supply guarantee ability of drug shortage. Departments cooperate to reduce the emergence of drug shortage and ensure the continuous access to safe and effective drugs in clinic.

OBJECTIVE： To investigate the situation and reasons of drug shortage in some medical institutions from Sichuan province. METHODS： A questionnaire survey was conducted among 78 medical institutions in Sichuan province by stratified random sampling. The situation of drug shortage were collected from Jan. 2015 to Jun. 2017， mainly including the basic information of medical institutions， drug shortage situation， specific drug shortage information and the reasons for drug shortage. Descriptive analysis of the information collected by the questionnaire was carried out， and Logistic regression analysis of the data by SPSS 20.0 software was adopted to find out the key factors affecting drug shortage. RESULTS & CONCLUSIONS： Totally 78 medical institutions include 13 third-level hospitals， 22 second-level hospitals and 43 primary medical institutions （10 community health service centers， 33 township health centers）. A total of 78 questionnaires were sent out， and the recovery rate and effective rate both were 100％. Among them， 68 medical institutions reported 206 shortage drugs totally， involving 240 specifications. The prices of more than 88.34％ of the shortage drug were less than 50 yuan. Main types of shortage drugs included anti-infective drugs， central nervous system drugs and cardiovascular system drugs， and most of them were purchased directly through internet. The proportion of temporary shortage （shortage time＜3 months） and long-term shortage （shortage time＞12 months） was relatively high （more than 68％ in total）. Drug supply and medical institutions’own factors were two main causes of drug shortage. Logistic regression analysis showed that main factors affecting the time of drug shortage were hospital drug purchase process， location of medical institution and drug purchase price. The main factors affecting the specifications of drug shortage in medical institutions were the process of drug purchase， the limitation of hospital purchase catalogue， primary or non-primary medical institution， comprehensive or specialized hospitals. It is suggested that medical institutions in this region can reduce the drug shortage caused by their own reasons by building a platform for drug information management， optimizing drug purchase catalogues and plans， strengthening the management of pharmacy inventory and establishing a regulatory system for distribution enterprises.

Objective To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM).Methods This was a 26-week,randomized,open-label,parallel-group,treat-to-target trial in 560 Chinese subjects with T2DM (men/women:274/263,mean age 56 years,mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs).Subjects were randomized 2:1 to once-daily IDeg (373 subjects) or IGlar(187 subjects),both in combination with metformin.The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks.Results Mean HbA1c decreased from 8.2％ in both groups to 6.9％ in IDeg and 7.0％ in IGlar,respectively.Estimated treatment difference (ETD) of IDegIGlar in change from baseline was-0.10％ points (95％ CI-0.25-0.05).The proportion of subjects achieving HbA1c ＜ 7.0％ was 56.3％ and 49.7％ with IDeg and IGlar,respectively [estimated odds ratio of IDeg/IGlar:1.26 (95 ％ CI 0.88-1.82)].Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar,respectively [estimated rateratio of IDeg/IGlar 0.69 (95％ CI 0.46-1.03),and 0.43 (95％ CI 0.19-0.97)].No differences in other safety parameters were found between the two groups.Conclusions IDeg was non-inferior to IGlar in terms of glycaemic control,and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia.IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment.Clinical trail registration Clinicaltrials.gov,NCT01849289.

OBJECTIVETo explore the effect and mechanism of acupoint sticking of Chuanfuling (CFL) in dog-days (the hottest periods of the year) in preventing and treating children asthma in remission stage.

METHODSNinety patients were divided into three groups, 30 in each. Patients in the CFL group were treated with CFL sticking, in the Western medicine (WM) group treated with Pulmicort inhalation, and in the control group was untreated. The clinical effect and indexes of humoral immunity (IgE, IgA, IgG) and cellular immunity (Eos, IL-4, IFN-gamma) before and after treatment were observed.

RESULTSAfter treatment in the CFL group all the immune parameters were significantly improved (P<0.05 or P<0.01), all were better than those in the control group (P<0.05 or P<0.01), and the effect on IgA and IgG was better than that in the WM group. In the WM group after treatment, improvement was shown on the IgE and cellular immune parameters with signifian difference (P<0.05 or P<0.01), better than those in the control group (P<0.05 or P<0.01). Besides, significant difference was shown in comparing IL-4 level between the WM group and the CFL group (P<0.05).

CONCLUSIONCFL sticking in dog-days could significantly improve the immune function in children with asthma to alleviate and control the attack.

Acupuncture Points ; Adjuvants, Immunologic ; administration & dosage ; Administration, Cutaneous ; Anti-Asthmatic Agents ; administration & dosage ; Asthma ; drug therapy ; immunology ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; Interleukin-4 ; blood ; Male ; Phytotherapy ; Seasons

Objective To evaluate the clinical efficacy and safety of sibutramine (Reductile )in Chinese obese patients. Methods Obese adults (BMI 27～45 kg/m 2) in six research centers received sibutamine 10 mg or placebo one tablet each day with a controlled-energy diet for 24 weeks by randomized, double-blinded, placebo-controlled study. Results For intent-to-treat analysis, 125 sibutramine-treated subjects and 126 placebo-treated subjects were evaluated. After 24 weeks, sibutramine-treated patients lost more weight (6.52?3.95)kg than placebo-treated patients (3.18?3.59)kg(P