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.

Objective To investigate the clinical efficacy of a compound oral sulfate solution for preoperative bowel cleansing in colonic polyp patients.Methods Patients who underwent colonoscopic polypectomy were divided into control group and treatment group according to cohort method methods.Patients in the control group were given compound polyethylene glycol electrolyte powder.They started taking it 4-6 hours before colonoscopy and completed the 4 liters of solution within 2 hours.Patients in the treatment group were given a compound oral sulfate solution.They took 1.5 liters of the solution the evening before surgery and repeated the same dosage on the day of the operation.Intestinal cleanliness was assessed using the Boston bowel preparation scale(BBPS),bowel preparation compliance,drug tolerance,patient satisfaction,and incidence of adverse drug reactions were compared between the two groups.Results Control group and treatment group each consisted of 40 cases.The total BBPS scores for the control group and treatment group were(6.68±1.19)and(7.43±1.23)points,respectively.This difference was statistically significant(P＜0.01).Medication compliance rates in the control group and treatment group were 70.00％(28 cases/40 cases)and 95.00％(38 cases/40 cases),respectively;movement compliance rates were 67.50％(27 cases/40 cases)and 97.50％(39 cases/40 cases)in the two groups,while medication tolerance rates were 67.50％(27 cases/40 cases)and 90.00％(36 cases/40 cases);patient satisfaction with bowel preparation were(1.89±0.75)and(2.42±0.43)points for the control and treatment groups,respectively;statistically significant differences were found between the control and treatment groups in all the above indicators(P＜0.05,P＜0.01,P＜0.001).The main adverse drug reactions in the control and treatment groups were nausea and vomiting,with occurrence rates of 10.00％(4 cases/40 cases)and 5.00％(2 cases/40 cases),respectively.The comparison of adverse drug reactions occurrence rate between the two groups showed no statistically significant difference(P＞0.05).Conclusion Taking compound oral sulfate solution for intestinal preparation,the intestinal cleaning effect is better than that of compound polyethylene glycol electrolyte powder,and the patient's compliance and drug tolerance are higher,and the patient's satisfaction can be effectively improved.

Gastrointestinal dyskinesia is a central factor contributing to the development of functional dyspepsia(FD),which is characterized by the rupture of the gastrointestinal nerve-Cajal interstitial cell-smooth muscle network.Gan Yu Pi Xu are similar to endoplasmic reticulum stress(ERs)-mitochondrial autophagy homeostasis imbalance.Mitochondrial autophagy disorders are the biological basis of Pi Xu,and Gan Yu is the macroscopic manifestation of ERs,and regulation of ERs-mitochondrial autophagy pathway is an important way to prevent and control FD.In this paper,we start from the theory of"liver-spleen correlation",combine the changes of endoplasmic reticulum and mitochondria in the process of gastrointestinal dyskinesia,reveal the correlation between the pathogenesis of Gan Yu Pi Xu and the autophagy of ERs and mitochondria,and elucidate the mechanism of gastrointestinal dyskinesia by the method of Shu Gan Jian Pi,so as to provide a new point of view for the treatment of gastrointestinal dyskinesia in FD.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To detect the changes of mitophagy level in rats with endplate cartilage degeneration induced by spinal instability,and explore the role of PINK1/Parkin-mediated mitophagy in endplate cartilage and intervertebral disc degeneration.Methods The rat spinal instability model was established by surgically removing the superspinal and interspinal ligaments of L2 to L5,and cleaning the bilateral articular processes of the L2 to L5.Eighteen SD rats were divided into the normal group,the degenerative group,and the carbonyl cyanide 3-chlorophenylhydrazone(CCCP)group,with 6 rats in each group.The rats in the normal group had no special treatment,the rats in the degenerative group constructed a rat spinal instability model,and the rats in the CCCP group were injected with 5 μL of CCCP(10 μmol/L)in the intervertebral disc after the construction of spinal instability model.The changes of histomorphology in the endplate cartilage and intervertebral disc were abserved by HE staining,and the change of extracellular matrix of endplate cartilage was observed by safranin O-fast green staining.RT-PCR detected the mRNA expression of type Ⅱ collagen(COL-2A),aggrecan(ACAN),PINK1 and Parkin in each group.The changes of the protein expression levels of COL-2A,ACAN,PINK1,Parkin and mitochondrial membrane proteins of Tomm20 and Timm23 were detected by Western blot.Results Compared with the normal group,the intervertebral disc nucleus pulposus of rats in the degenerative group was significantly destroyed and the secretion of extracellular matrix of endplate chondrocytes decreased;while the structure of intervertebral discs for rats in the CCCP group was more intact,and the secretion of extracellular matrix of endplate chondrocytes was significantly increased compared with that in the degenerative group.Compared with the normal group,the expression of COL-2A and ACAN in endplate cartilage tissues of rats in the degenerative group were significantly down-regulated(P<0.05),the expression of mitochon-drial autophagy-related genes of PINK1 and Parkin were significantly decreased(P<0.05),and the expression of mitochondrial membrane proteins of Tomm20 and Timm23 were increased(P<0.05).Compared with the degenerative group,the expression of COL-2A,ACAN,PINKI and Parkin in the endplate cartilage tissue of rats in the CCCP group were significantly up-regulated(P<0.05),and the protein levels of Tomm20 and Timm23 were significantly down-regulated(P<0.05).Conclusion Rat spinal instability leads to a decrease level of mitophagy mediated by PINK1/Parkin signaling pathway in endplate cartilage,thereby inducing endplate cartilage and intervertebral disc degeneration,and the activation of mitophagy can significantly reduce endplate cartilage and intervertebral disc degeneration.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To observe the safety and the feasibility of biplane transrectal ultrasonography-guided transperineal biopsy for diagnosing women pelvic space-occupying lesions.Methods Data of 14 female patients with pelvic space-occupying lesions who underwent biplane transrectal ultrasonography-guided transperineal biopsy were retrospectively analyzed.The location of pelvic space-occupying lesions,the causes for not performing biopsy transabdominally nor transvaginally,the time consuming and complications of biplane transrectal ultrasonography-guided transperineal biopsy as well as pathological results were collected.Results Among 14 cases,there were 4 cases of rectum mass,3 cases of unilateral or bilateral ovaries masses,5 cases of cervix or lower uterus mass,1 case of mass at the lateral wall of the vagina and 1 case of mass at the posterior part of the bladder.Since vagina abnormalities including severe bleeding,fungal infections,deformities,edema or after vaginal resection,or deep location of lesions and high risk of intestinal tubes injuries,transabdominal or transvaginal puncturing and biopsy were not performed.The time consuming of puncturing and biopsy were(29.50±6.05)min.During the procedures,bleeding in the puncturing tract and vagal reflex occurred each in 1 case,while no obvious complication was observed during 6-month follow-up.Biopsy pathology reported 5 cases of squamous cell carcinoma,2 cases of high grade serous carcinoma,1 case of malignant melanoma,1 case of low grade serous carcinoma,1 case of adenocarcinoma and 1 case of spindle cell tumor,as well as 3 cases of chronic inflammation,all were consistent to post operation pathology or follow-up results.Conclusion Biplane transrectal ultrasonography-guided transperineal biopsy was safe and feasible for diagnosing women pelvic space-occupying lesions.

A quartz crystal microbalance(QCM)-systematic evolution of ligands by the exponential en-richment(SELEX)technique was developed to screen out aptamers with high affinity for arsenic(Ⅲ).A random single strand DNA library was designed and fixed on the mercaptoethylamine-modified crystal plate with arsenic(Ⅲ)as the target,and the free aptamer was captured in the solution,and the QCM-SELEX screening method was constructed.After 6 rounds of screening,the secondary library was se-quenced with high throughput method,and the 6S1 dissociation coefficient Kd value was 0.36 μmol/L based on QCM resonance frequency.Using 6S1 as a probe,the QCM biosensor was constructed for the detection of arsenic(Ⅲ).The sensor has a good linear relationship in the range of 0.01 μmol/L～0.2μmol/L,and the detection limit of arsenic(Ⅲ)is 5.2 nmol/L(3σ),indicatinggood selectivity.