ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Objective To systematically evaluate the risk factors for persistent cough after lung resection, providing a theoretical basis for preventing persistent postoperative cough. Methods The Cochrane Library, Web of Science, EMbase, PubMed, Chinese Biomedical Literature Database, Wanfang, CNKI, and VIP databases were searched for studies related to risk factors for persistent cough after lung resection. The search period was from database inception to March 30, 2023. Two researchers independently screened the literature, extracted data, and performed quality assessment. RevMan 5.3 software was used for meta-analysis. Results A total of 17 articles with 3 698 patients were included. Meta-analysis results showed that females [OR=3.10, 95%CI (1.99, 4.81), P<0.001], age [OR=1.72, 95%CI (1.33, 2.21), P<0.001], right-sided lung surgery [OR=2.36, 95%CI (1.80, 3.10), P<0.001], lobectomy [OR=3.40, 95%CI (2.47, 4.68), P<0.001], upper lobectomy [OR=8.19, 95%CI (3.87, 17.36), P<0.001], lymph node dissection [OR=3.59, 95%CI (2.72, 4.72), P<0.001], bronchial stump closure method [OR=5.19, 95%CI (1.79, 16.07), P=0.002], and postoperative gastric acid reflux [OR=6.24, 95%CI (3.27, 11.91), P<0.001] were risk factors for persistent cough after lung resection, while smoking history was a protective factor against postoperative cough [OR=0.59, 95%CI (0.45, 0.77), P<0.001]. In addition, the quality of life score of patients with postoperative cough decreased compared with that before surgery [MD=1.50, 95%CI (0.14, 2.86), P=0.03]. Conclusion Current evidence suggests that females, age, right-sided lung surgery, lobectomy, upper lobectomy, lymph node dissection, bronchial stump closure method (stapler closure), and postoperative gastric acid reflux are independent risk factors for persistent postoperative cough in lung resection patients, while smoking history may be a protective factor against postoperative cough. This provides evidence-based information for clinical medical staff on how to prevent and reduce persistent postoperative cough in patients and improve their quality of life in the future.

ObjectiveTo investigate the effects of Xinfeng capsules combined with chronic disease management of traditional Chinese medicine （TCM） on rapid disease control and short-term prognosis of patients with rheumatoid arthritis （RA）. MethodsA total of 80 RA patients hospitalized in the Department of Rheumatology of The First Affiliated Hospital of Anhui University of Chinese Medicine from January 2022 to March 2024 were enrolled and randomly divided into an observation group （40 cases） and a control group （40 cases）. The control group was treated with conventional methotrexate combined with standard chronic disease management， while the observation group was additionally treated with Xinfeng Capsules combined with TCM chronic disease management. The treatment course lasted 24 weeks. The outcomes were compared between two groups， including disease activity ［28-joint disease activity score （DAS28）， clinical disease activity index （CDAI）， simplified disease activity index （SDAI）］， visual analogue scale （VAS） for pain， TCM syndrome score， tender joint count （TJC）， swollen joint count （SJC）， morning stiffness duration， Health Assessment Questionnaire （HAQ）， Self-Rating Anxiety Scale （SAS）， Self-Rating Depression Scale （SDS）， American College of Rheumatology （ACR） 20%， 50% and 70% response rates （ACR20/50/70）， erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide antibody （CCP-Ab）， interleukin （IL）-6， IL-1β， tumor necrosis factor-α （TNF-α）， and serum immunoglobulin G （IgG）. The Chronic Disease Self-Management Scale （CDSMS） was used to evaluate patients’ self-management ability， self-care ability， and nursing satisfaction. Patients were followed up for 12 weeks to assess prognosis， and COX regression analysis was performed to determine the impact on short-term prognosis. ResultsAfter treatment， TJC， SJC， morning stiffness duration， DAS28， CDAI， SDAI， VAS， TCM syndrome score， ESR， hs-CRP， RF， CCP-Ab， IL-6， IL-1β， TNF-α， IgG， HAQ， SAS， SDS， chronic disease self-management behavior， self-efficacy， and self-care ability all improved significantly in both groups compared with baseline （P<0.05，P<0.01）. Compared with the control group， the observation group showed more significant improvements in TJC， SJC， morning stiffness duration， DAS28， CDAI， SDAI， VAS， TCM syndrome score， ESR， IL-1β， IgG， HAQ， SAS， SDS， self-care ability， chronic disease self-management behavior， and self-efficacy （P<0.05 or P<0.01）. The ACR70 response rate and nursing satisfaction were significantly higher in the observation group than in the control group （P<0.01）. COX regression analysis showed that Xinfeng capsules combined with TCM chronic disease management reduced the risk of poor short-term prognosis in RA patients. ConclusionXinfeng capsules combined with TCM chronic disease management facilitates rapid disease control in RA patients， effectively improves short-term prognosis， and plays an important role in the treatment of the disease.

Objective To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis.Metods From January 2018 to December 2021,a multicenter randomized controlled study was per-formed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method.There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of(41.20±5.50)years old;the course of disease ranged from 1 to 14 days with an average of(5.24±1.35)days;they were treated once every other day for 2 weeks.There were 96 patients in control group,including 33 males and 63 females,aged from 26 to 60 years old with an average of(43.35±7.75)years old;the course of disease ranged from 1 to 14 days with an average of(5.86±1.48)days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks.Visual analogue scale(VAS)and Hospital for Surgery Scoring System(HSS)elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2(HSS2)was compared before treatment and the final treatment.Results All patients were followed up for 10 to 14 days with an average of(12±1.6)days.VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment.VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment.HSS of treatment group were signifi-cantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).On the 5th day after treat-ment,the external and internal rotation angles of elbow in treatment group were(66.41±12.69)° and(66.35±13.54)°,while those in control group were(62.08±16.03)° and(61.77±16.35)°.On the 7th day after treatment,the external and internal ro-tation angles of elbow were(69.79±12.64)° and(70.02±13.55)° in treatment group,and(65.28±15.86)° and(65.09± 16.67)° in control group.Elbow joint motion in treatment group was higher than that in control group(P＜0.05).On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were(39.43±15.94)°and(46.68±11.10)° in treatment group,and(38.51±18.49)° and(44.27±13.58)° in control group.On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were(42.52±16.50)° and(49.23±10.96)° in treatment group,and(41.18±20.09)° and(46.64±14.63)° in control group.The motion of wrist joint in treatment group was higher than that in control group(P＜0.05).On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P＜0.05).There was no significant difference in elbow tenderness between two groups at each time point(P＞0.05).Conclusion Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of exter-nal humeral epicondylitis.Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.

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 investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.