ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Objective To explore the impact of lung cancer screening on the changes of health risk behaviors in 420 high-risk populations. Methods Among the 420 high-risk subjects who underwent lung cancer screening in the hospital from January 2022 to February 2024 were included and underwent low-dose computed tomography (LDCT) screening and were followed up for 1 year. Multivariate logistic regression analysis was used to analyze the association between lung cancer screening and changes in health risk behaviors. Results Compared with the baseline situation, the smoking rate, alcohol drinking rate and long-term exposure to asbestos and other carcinogens were lower during 1-year follow-up, and the regular physical examination rate was increased (P<0.05). In this study, health-risk behaviors of 176 subjects changed during 1-year follow-up, and women, subjects who consulted physicians about physical condition, subjects having positive nodules and subjects having previous history of lung disease accounted for higher proportions (P<0.05). Logistic regression analysis suggested that women, consulting physicians about their physical condition, having positive nodules and having previous history of lung disease were more likely to change health risk behaviors (P<0.05). Conclusion Lung cancer screening prompts high-risk individuals (smokers, drinkers, those with long-term exposure to asbestos and other carcinogens, and those without regular physical examination) to change their health risk behaviors. Women, those who actively consult physicians about their physical condition, those with positive nodules and those with previous history of lung disease are more likely to change their unhealthy habits through screening than other individuals.

Objective To establish a HPLC method for determining thimerosal compounds in eye drops. Methods A gradient HPLC system was used in the quantitative analysis of thimerosal compounds on Shiseido MGII C₁₈ column （4.6 mm×250 mm，5 μm）, using 1% triethylamine solution （pH adjusted to 3.0 with phosphate） as mobile phase A, the methanol as mobile phase B, gradient elution, The column temperature was 40 ℃, the detection wavelength was 222 nm, the flow rate was 1 ml/min and the injection volume was 20 µl. Results The established method had good linearity within the concentration range of 4.3-216.7 μg/ml （r>0.999） for thimerosal, with average recoveries was 102.1%, RSD2.7%. Conclusion This method was simple, accurate and highly specific, and could be used for determination of thimerosal compound in eye drops.

OBJECTIVE: Microcirculatory disturbance is pathologically critical to acute pancreatitis (AP), which can be effectively alleviated by traditional Chinese medicine (TCM) formulas that activate blood flow. However, there has been no evidence-based research to date. Therefore, a well-designed systematic review and meta-analysis is necessary to elucidate the therapeutic transformative benefit of improving microcirculation during AP. This study aims to confirm the therapeutic efficacy of TCM formulas and explore the potential mechanisms underlying their effects on AP treatment. METHODS: Studies from eight databases including Pubmed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and Chinese VIP, were screened for the eligible randomized controlled trials (RCTs). The APACHE II score and effectiveness rate were set as primary outcomes, while mortality rate, complications, total hospital stays, serum amylase recovery time, the time until the disappearance of abdominal pain, microcirculation indicators, and inflammation indicators were chosen as secondary outcomes. A systematic review and meta-analysis were subsequently conducted. Network pharmacology analysis was performed to analyze potential bioactive components with relevant targets of the core herbs included in the TCM formulas for activating blood flow. RESULTS: A total of 51 RCTs (n = 3 721) were included. Compared with conventional western medical treatments alone, TCM groups were associated with lower APACHE II score (SMD =  - 1.36, 95% CI: -2.01 to - 0.71, P = 0.000) and higher effectiveness rate (RR: 1.22, 95% CI: 1.18 to 1.26, P = 0.000). Furthermore, the formulas for activating blood flow demonstrated significant efficacy in improving both microcirculation and inflammation indicators. Additionally, six core Chinese herbal medicines including Rhei Radix et Rhizoma with the highest frequency, Aurantii Fructus Immaturus, Paeoniae Radix Rubra, Bupleuri Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Corydalis Rhizoma were filtered out from the adopted TCM formulas. Finally, 166 shared targets between the six herbs and AP were identified. KEGG analysis indicated that lipid and atherosclerosis pathway is highly related to microcirculation. CONCLUSION TCM formulas for activating blood flow significantly improve microcirculation and alleviate AP. Further high-quality, well-designed RCTs and deep mechanism exploration are required.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4. It is transmitted in an autosomal dominant manner and is characterized by motor dysfunction, cognitive decline, and emotional disturbances. To date, there are no curative treatments for HD have been developed; current therapeutic approaches focus on symptom relief and comprehensive care through coordinated pharmacological and nonpharmacological methods to manage the diverse phenotypes of the disease. International clinical guidelines for the treatment of HD are continually being revised in an effort to enhance care within a multidisciplinary framework. Additionally, innovative gene and cell therapy strategies are being actively researched and developed to address the complexities of the disorder and improve treatment outcomes. This review endeavours to elucidate the current and emerging gene and cell therapy strategies for HD, offering a detailed insight into the complexities of the disorder and looking forward to future treatment paradigms. Considering the complexity of the underlying mechanisms driving HD, a synergistic treatment strategy that integrates various factors-such as distinct cell types, epigenetic patterns, genetic components, and methods to improve the cerebral microenvironment-may significantly enhance therapeutic outcomes. In the future, we eagerly anticipate ongoing innovations in interdisciplinary research that will bring profound advancements and refinements in the treatment of HD.
Huntington Disease/pathology* ; Humans ; Genetic Therapy/methods* ; Animals ; Huntingtin Protein/genetics* ; Cell- and Tissue-Based Therapy/methods*

Objective:A gas chromatographic method was established for the determination of alcohol and phenolic bacteriostatic agents(chlorobutanol,phenol,benzyl alcohol,phenethyl alcohol,phenoxyethanol,4-chloro-o-cresol and thymol)in eye drops for related quality control.Methods:A capillary column with(5%phenyl)methylsilox-ane as the fixing solution.The initial temperature was 60℃and keep for 10 min.The temperature was rised to 150℃at a rate of 20℃·min-1 and keep for 3 min,Next,the temperature was rised to 230℃at a rate of 50℃·min-1 and keep for 2 min.The detector temperature was 250℃,the inlet temperature was 200℃,and the detector was FID.Direct injection of 1 μL was used for injection.Results:The were a good linear relationship between peak area and concentration in the concentration range of 0.05-1.0 mg·mL-1(chlorobutanol),0.05-1.0 mg·mL-1(phenol),0.1-2.0 mg·mL-1(benzyl alcohol),0.05-1.0 mg·mL-1(phenethyl alco-hol),0.05-1.0 mg·mL-1(phenoxyethanol),0.03-0.6 mg·mL-1(4-chloro-o-cresol)and 0.01-0.20 mg·mL-1(thymol)(r values were 0.999 7,0.999 6,0.999 5,0.999 5,0.999 5,0.999 5,0.999 5 and 0.999 5 respectively).The average recoveries of seven component were 103.4%,95.2%,98.4%,97.2%,97.9%,100.5%and 93.5%respectively.All meet the requirements of methodological research.According to the method,79 batches of samples were tested for alcohol and phenolic bacteriostatic agents.Chlorobutanol was detected in 8 batches of samples,and no other bacteriostatic agents were detected.Conclusion:This method meets the require-ments for specificity and sensitivity,and is suitable for the confirmation and determination of alcohol and phenolic antibacterial agents in eye drops.It can be used for related quality control.

Ovarian cancer,as one of the three major malignant tumors in gynecology,has a relatively high mortality rate.Traditional adjuvant chemotherapy has failed to significantly improve the survival rate of patients in the advanced stage due to its high drug resistance.Therefore,new treatment methods are urgently needed to improve the survival rate of patients.Cuproposis is a newly proposed form of cell death,which is caused by the accumulation of lipoylated protein and the loss of Fe-S cluster protein by copper overload,and it is expected to be a new treatment method for ovarian cancer to improve the prognosis of patients.Previous studies have shown that cuproptosis related genes are differentially expressed in ovarian cancer,which can guide personalized immunotherapy and participate in chemotherapy resistance.This article will review the correlation between the mechanisms related to cuproptosis and ovarian cancer,and explore whether it can provide new ideas for the treatment of ovarian cancer in the future.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. 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 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.