BACKGROUND:Recent research indicates that disc degeneration is closely related to abnormal stress load,and mechanotransduction proteins play a key role in it. OBJECTIVE:To investigate the role and mechanism of mechanotransduction proteins in the mechanotransduction process induced by abnormal mechanical stimulation in disc degeneration,and to summarize the current treatment strategies targeting mechanotransduction to delay intervertebral disc degeneration. METHODS:Using"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanics,signal transduction,protein,biomechanics"as Chinese search terms,and"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics"as English search terms,relevant literature in the PubMed and CNKI databases was searched.A total of 88 articles were ultimately included for review. RESULTS AND CONCLUSION:Disc cells can sense external mechanical stimulation through various mechanotransduction proteins and convert it into biological responses within the cells.These transduction proteins mainly include collagen proteins in the extracellular matrix,cell membrane surface receptors(such as integrins and ion channels),and cytoskeleton structural proteins.Their regulation of mechanotransduction processes primarily involves the activation of multiple pathways,such as the PI3K/AKT signaling pathway,nuclear factor-kB signaling pathway,and Ca2+/Calpain2/Caspase3 pathway.Mechanotransduction proteins play a key role in the mechanotransduction of disc cells.Abnormal expression of these proteins or resulting changes in the extracellular matrix environment can disrupt the mechanical balance of disc cells,leading to disc degeneration.In-depth study of the expression and regulatory mechanisms of mechanotransduction proteins in disc cells,and identification of key pathological links and therapeutic targets,is of significant importance for developing treatment strategies for disc degeneration.Current strategies to delay intervertebral disc degeneration by targeting mechanotransduction mainly include regulation of transduction proteins and improvement of the extracellular matrix.However,research in this area is still in its early stages.As research continues,new breakthroughs are expected in the regulation of disc degeneration by mechanotransduction proteins.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

【Objective】 To construct an acute toxoplasma encephalitis mouse model by observing the pathological changes in the hippocampus of mice infected with Toxoplasma gondii strain RH. 【Methods】 The quantitative RH Toxoplasma gondii (100, 500, and 1 000 trophozoites) were injected into the hippocampal CA1 region of mice by the stereotaxic surgery; the survival status of mice was observed. Giemsa staining was used to observe the changes of toxoplasma in mouse ascites and brain tissue homogenates. Nissl staining and HE staining were used to observe the pathological changes of hippocampal nerve tissue. The distribution of Toxoplasma gondii in brain tissue was observed by immunohistochemical ABC method. 【Results】 The RH Toxoplasma gondii infected mice showed obvious symptoms such as arched back, bristling hair, abdominal distension, subtle tremor and hemiplegia on the fourth day of infection. The survival of mice in 100 trophozoites group was longer, no trophozoites of Toxoplasma gondii were found in ascites, a few pseudocysts were found in brain tissue homogenates after infected for 96 hours, and more trophozoites were found after death. Nysl staining and HE staining showed more tissue necrosis foci and loss of nerve cells in CA1 area after infected 144 h. The injury aggravated with the prolongation of infection time. Toxoplasma trophozoites were found in ascites and brain homogenates of mice in 500 and 1000 trophozoites groups. Nissl staining revealed neuronal loss and massive necrosis in the hippocampus. HE staining showed necrosis and inflammatory cell infiltration. The brain tissue injury significantly aggravated compared with 100 trophozoites group. The distribution of Toxoplasma gondii in the necrotic foci was confirmed by immunohistochemistry. 【Conclusion】 The survival of 100 trophozoite mice infected with Toxoplasma gondii strain RH was longer, and the pathological changes of brain tissue gradually aggravated. The damage was relatively confined to the brain tissue, and the mice showed typical symptoms of toxoplasma encephalitis. Therefore, the mouse model of acute toxoplasma encephalitis can be constructed by localized infection of 100 toxoplasma trophozoites, which can lay a foundation for future research on the mechanism of toxoplasma injury to cranial nerves.

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
Animals ; Rats ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species ; Tumor Suppressor Protein p53/genetics* ; Signal Transduction ; Liver ; Aging ; Cell Cycle Proteins ; Interleukin-6

BACKGROUND: Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China. METHODS: Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up. RESULTS: The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05). CONCLUSIONS Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Abstract: Objective　By collecting and sorting the information of varicella cases reported in Liaoning Province from 2006 to 2021, the epidemiological characteristics were analyzed, and the monthly incidence data were predicted, so as to explore the prevention and control strategy of varicella disease in Liaoning Province. Methods　By collecting the characteristic information of varicella cases in Liaoning Province, epidemiological analysis was carried out on the regional, population, and temporal characteristics of varicella incidence. The monthly incidence data of varicella were fitted with Eviews software, seasonal ARIMA model was used for modeling, and models were selected according to SC and AIC. After modeling, the model was used to predict the incidence data in 2022. Results　The incidence rate of varicella in Liaoning Province has increased in recent years. The onset time was "bimodal distribution", with the main peak occurring from November to January of the next year and the secondary peak occurring from May to June. Since 2019, the onset age has shifted backward. From the original 0-<10 age group with the highest incidence rate, it shifted to the 10-<20 age group with the highest incidence rate. From 2006 to 2021, the incidence of varicella mainly concentrated in people aged 0 to <40 years old, and the incidence rate of the population over 40 years old showed a cliff-like decline. The incidence of chickenpox was higher in the central region of Liaoning Province, such as Shenyang, Dalian, Anshan and Panjin, and relatively low in Huludao, Jinzhou, Fuxin and Liaoyang. The distribution of the population was mainly students, followed by kindergartens and scattered children. ARIMA model of monthly incidence data was established by software as ARIMA (1, 0, 1) (1, 1, 1)12. Conclusions　The incidence rate of varicella in Liaoning Province has been rising in recent years. The incidence is obviously seasonal, and the age group of the affected population has moved backward. It is predicted that the incidence will continue to increase in 2022. The prevention and control of varicella should still be the current key work. In order to reduce the population incidence rate, two-dose vaccination strategies should be vigorously promoted the implementation of the, and the inclusion of varicella vaccine in the immunization program should be achieved as soon as possible.

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity

Objective To understand the distribution and antimicrobial resistance changes of bacteria isolated from pleural and peritoneal effusion in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Provincial Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacteria antimicrobial resistance surveillance method was imple-mented according to technical scheme of China Antimicrobial Resistance Surveillance System(CARSS),and WHO-NET 5.6 software was used to analyze the data of bacteria isolated from pleural and peritoneal effusion as well as antimicrobial susceptibility testing results.Results From 2012 to 2021,a total of 28 934 bacterial strains were iso-lated from specimens of pleural and peritoneal effusions from member units of Hunan Provincial Antimicrobial Re-sistance Surveillance System,with 5 752 strains from pleural effusion and 23 182 from peritoneal effusion.The top five bacteria isolated from pleural effusion were Escherichia coli(n=907,15.8％),Staphylococcus aureus(n=535,9.3％),Klebsiella pneumoniae(n=369,6.4％),Staphylococcus epidermidis(n=452,7.9％),and Staphy-lococcus haemolyticus(n=285,5.0％).The detection rate of methicillin-resistant Staphylococcus aureus(MR-SA)from pleural effusion was 24.3％-39.2％,and that of methicillin-resistant coagulase negative Staphylococcus(MRCNS)was 58.8％-77.1％.The top five bacteria isolated from peritoneal effusion were Escherichia coli(n=8 264,35.6％),Klebsiella pneumoniae(n=2 074,9.0％),Enterococcus faecium(n=1 458,6.3％),Staphylo-coccus epidermidis(n=1 383,6.0％),and Pseudomonas aeruginosa(n=1 152,5.0％).The detection rate of MRSA from peritoneal effusion was 22.1％-52.4％,which presented a decreasing trend(P=0.004).The detec-tion rate of MRCNS was 60.4％-79.4％.The resistance rates of Enterobacterales from peritoneal effusion to ce-fazolin,cefuroxime,ceftriaxone and cefepime all showed decreasing trends(all P＜0.05).Vancomycin-,linezo-lid-,and teicoplanin-resistant Staphylococcus strains were not found in pleural and peritoneal effusions.The resis-tance rates of Enterococcus faecium to most tested antimicrobial agents were higher than those of Enterococcus fae-calis.The resistance rates of Enterobacterales to imipenem and meropenem were ≤8.5％.The resistance rates of non-fermentative Gram-negative bacilli to imipenem and meropenem were ≤43.3％.Conclusion The data structure of Hunan Antimicrobial Resistance Surveillance System for pleural and peritoneal effusions from 2012 to 2021 is relatively complete.The constituent and antimicrobial susceptibility of isolated pathogenic bacteria vary in different years.

Objective To understand the epidemiology of clinically isolated Acinetobacter baumannii(A.bauma-nnii)in Hunan Province.Methods Bacterial antimicrobial resistance surveillance was carried out according to the requirements of the technical program of National Antimicrobial Resistance Surveillance System.Clinical data of Acinetobacter spp.reported to Hunan Provincial Antimicrobial Resistance Surveillance System by multiple centers in Hunan Province from 2012 to 2021 were summarized and analyzed with reference to the standards of the American Clinical and Laboratory Standards Institute.Results A total of 169 438 strains of Acinetobacter spp.were detected during the 10-year period,with the detection rate of A.baumannii being the highest(82.74％).70 923 strains(53.63％)of carbapenem-resistant A.baumannii(CRAB)and 58 149 strains(43.97％)of carbapenem-sensitive A.baumannii(CSAB)were detected respectively.Both CRAB and CSAB were detected most frequently in the age group＞70 years,which were 34.44％and 32.02％,respectively.The percentage of CRAB and CSAB detected in the intensive care unit were 34.80％and 11.31％,respectively.CRAB and CSAB were mainly isolated from spu-tum/bronchoalveolar lavage fluid,followed by pus/secretion,urine,and blood.The resistance rates of CRAB to commonly used antimicrobial agents didn't change much during the 10-year period.Resistance rates of CRAB to ceftazidime and cefepime were both＞84％,to ampicillin/sulbactam and piperacillin/tazobactam were both＞82％,to aminoglycosides and quinolones were both＞59％,to minocycline and polymyxin B were 15.9％-25.0％and 1.3％-6.9％,respectively.CSAB were sensitive to commonly used antimicrobial agents.Conclusion The isolation rate of CRAB is high and there is no significant change in resistance to commonly used antimicrobial agents.

Objective:To summarize and analyze the clinical features of McCune-Albright syndrome (MAS) in 26 children, to improve the understanding of MAS diagnosis and treatment, and to achieve early clinical diagnosis of MAS.Methods:The clinical data of 26 children with MAS treated in Department of Pediatrics, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from August 2011 to June 2021 were retrospectively analyzed.Their clinical characteristics were summarized and studied. t-test, Mann- Whitney U test, χ 2 test or Fisher′ s exact probability method was used for comparison between groups. Results:(1) Among the 26 MAS patients enrolled, there were 22 females and 4 males.The average onset age of female and male patients was (5.87±2.94) years old and (7.48±3.36) years old, respectively.(2) In female patients, there were 7 cases with the typical triad and 15 cases with the atypical triad.(3) Female patients had the first symptom of vaginal bleeding (8/22) and breast development (14/22). Among the 4 male children, 1 case had " fracture" and 3 cases " lagged behind their peers in height" at the first visit.(4) Compared with the breast development group, the vaginal bleeding group had an earlier onset age[(4.06±1.88) years old vs.(7.82±1.82) years old] ( t=5.023, P<0.001), earlier bone maturation[(1.26±0.07) vs.(1.09±0.13)] ( t=2.933, P<0.05), a greatly lowered predicted adult height[(-2.16±0.98) SDS vs.(-0.96±1.09) SDS]( t=1.352, P<0.05), a lower blood phosphorus level[(1.41±0.14) nmol/L vs.(1.67±0.24) nmol/L] ( t=1.941, P<0.05), and a significantly elevated alkaline phosphatase level[339(313, 656) U/L vs.243(205, 452) U/L] ( U=1.000, P<0.05). All patients (8 cases) in the vaginal bleeding group had fibrous dysplasia of bone.(5) Ten patients progressed to central precocious puberty (CPP). They showed an older average age of onset[(7.27±2.69)years old vs.(4.69±2.68)years old] ( U=44.000, P<0.05), significantly earlier bone maturation at diagnosis[(1.23±0.11) vs.(1.01±0.13)] ( t=1.834, P<0.05), and a lower predicted adult height[(152.00±4.62) cm vs.(162.10±6.91) cm] ( t=3.805, P<0.05), compared with those who did not progress to CPP.(6) Eleven children developed polyostotic fibrous dysplasia of bone, and most common type (8 cases) was polyostotic fibrous dysplasia of bone, primarily at lower limb bones and skulls.(7) Of the 26 children, 20 cases had scattered Café au lait pigments on the skin.The Café au lait pigmented skin lesions in 35% (7/20) cases crossed the midline. Conclusions:With complicated clinical manifestations, MAS is more common and occurs earlier in girls than boys.It is difficult to clinically diagnose MAS in boys due to the insidious onset and atypical symptoms.Female MAS patients with vaginal bleeding as the first symptom usually have an early age of onset, advanced bone age and lower predicted adult height, so they should be monitored and evaluated clinically.Vaginal bleeding is significantly associated with polyostotic fiber dysplasia of bone in MAS patients.Therefore, it is recommended that patients with vaginal bleeding should undergo a routine bone single-photon emission computed tomography scan.This helps understand the situation of occult fiber dysplasia of bone.Patients with later diagnosis and advanced bone age should be aware of the possibility of progression to CPP.