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”.

Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas with distinct clinical and pathological features. In recent years, advancements in molecular biology techniques have led to a deeper understanding of the molecular mechanisms underlying PACC. Progress in imaging, endoscopic, and molecular diagnostic technologies has improved the early detection rate of PACC. The primary treatment modalities for PACC include surgical resection, chemotherapy, targeted therapy and immunotherapy; however, the therapeutic efficacy still requires further improvement. This article reviews the current research status of PACC, covering its epidemiology, pathological characteristics, molecular alterations, diagnostic methods, and treatment strategies, and discusses the controversies and future directions in PACC research.

Objective To investigate the clinical characteristics,treatment responses,and prognosis of patients with idiopathic multicentric Castleman disease(iMCD)complicated by autoimmune hemolytic anemia(AIHA). Methods The patients diagnosed with iMCD in Peking Union Medical College Hospital from January 2010 to December 2023 and having complete baseline blood routine data were retrospectively enrolled in the study.The iMCD patients were further assigned into AIHA and non-AIHA groups based on baseline laboratory examinations,and the clinical characteristics and prognosis were compared between the two groups. Results A total of 341 patients with iMCD were enrolled in this study,including 277(81.2%)exhibiting anemia at baseline.Five(1.8%)patients were identified as having iMCD-AIHA,all of whom were iMCD-not otherwise specified type complicated by warm antibody-type AIHA,and two of them were simultaneously diagnosed with Evans syndrome.The timing relationship between the first onset of AIHA and iMCD diagnosis varied,with 2 patients experiencing their first hemolytic episode prior to the diagnosis of iMCD.In terms of treatment,the therapy targeting iMCD was effective in alleviating AIHA.The AIHA group had a poorer prognosis(HR=4.61,95% CI=1.08-19.80,P=0.040)and a lower 5-year survival rate(90% vs.60%,P=0.024)than the non-AIHA group.Conclusions iMCD-AIHA is clinically rare,and AIHA can occur at different stages of iMCD.Although the primary treatment principle remains targeting iMCD,great attention should be paid to the exacerbation of immune dysfunction caused by AIHA and the possible adverse prognosis it may bring.
Humans ; Anemia, Hemolytic, Autoimmune/diagnosis* ; Castleman Disease/diagnosis* ; Retrospective Studies ; Male ; Female ; Prognosis ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent

Objective:To understand the prevalence of frailty and the importance of its influencing factors in adult population in Shaanxi Province.Methods:The data were from Shaanxi baseline survey of natural population cohort study in northwest China during 2018-2019. The frailty index (FI) was constructed to evaluate the frailty status of the population, and XGboost model combined with Shapley method was used to analyze the importance of the sociodemographic and life behavior factors affecting the prevalence of frailty by gender and age.Results:A total of 25 079 subjects were included, in whom 964 (3.8%) had frailty, and there was no significant difference in the overall prevalence of frailty between women (3.9%) and men (3.8%) ( P=0.629), but there was a gender specific difference in the distribution of FI ( P<0.001), and the proportion of the pre-frailty in men was higher than that in women. The prevalence of frailty increased with age ( P<0.001), the prevalence of frailty were 1.3%, 2.5% and 7.8% in young, middle-aged and elderly women, respectively, and 1.9%, 2.7% and 5.5% in young, middle-aged and elderly men, respectively. Sociodemographic characteristics and lifestyle patterns were both influencing factors for the prevalence of frailty, but their importance varied with gender and age. The top five contributing factors were education level, staying up late, annual family income level, sedentary time and marital status in young women, and staying up late, smoking, annual family income level, sedentary time and drinking in young men. The top five contributing factors were education level, annual family income level, passive exposure to smoking, staying up late, and sedentary time in middle-aged women, and annual family income level, education level, sedentary time, staying up late and drinking in middle-aged men. The top five contributing factors were annual family income level, passive exposure to smoking, sedentary time, marital status, and smartphone use in elderly women, and education level, annual family income level, smoking, smartphone use and sedentary time in elderly men. Conclusions:There are gender specific differences in the distribution of FI in Shaanxi. The prevalence of frailty increased with age, but young and middle-aged people also have frailty risk. The prevalence of frailty in young men was mainly related to unhealthy life behaviors, such as staying up late, smoking, sedentary behavior and drinking, while the prevalence of frailty in middle-aged and elderly men and women were more affected by sociodemographic factors, such as education level, economic status and marital status.

AIM:To explore the therapeutic effect of Tongfeng-Qingli mixture(TFQLM)and its mechanism in hyperuricemic(HUA)rats based on uric acid(UA)transporter and Janus kinase 2(JAK2)/signal transducer and acti-vator of transcription 3(STAT3)signaling pathway.METHODS:(1)In vivo experiment:36 male SD rats were random-ly divided into control(CON)group,model(MOD)group,benzbromarone(BEN)group,low-dose TFQLM(TFQLM-L)group,medium-dose TFQLM(TFQLM-M)group,and high-dose TFQLM(TFQLM-H)group,with 6 rats in each group.In all groups except CON group,HUA was induced in rats by giving hypoxanthine(HP)combined with potassium oxybate(OP)for 35 consecutive days.The rats in CON group were given sodium carboxymethyl cellulose solution by gavage.A fully automatic biochemistry analyzer was used to detecte serum UA,serum creatinine(SCr)and blood urea nitrogen(BUN)levels.The xanthine oxidase(XOD)and adenosine deaminase(ADA)levels in the liver were detected by ELISA kits.The histopathological changes of kidneys were observed by HE staining.Immunohistochemistry was performed to de-tect urate transporter 1(URAT1)and glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and OAT3 ex-pression in the kidney.Western blot was used to measure the protein levels of URAT1,GLUT9,OAT1,OAT3,interleu-kin-6(IL-6),tumor necrosis factor-α(TNF-α),JAK2,p-JAK2,STAT3,p-STAT3 and repressor of cytokine signaling 3(SOCS3)in the kidney.(2)In vitro experiments:HUA cellular model was established by UA stimulation in HK2 cells,and the protein levels of URAT1,GLUT9,OAT1,OAT3,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3,and SOCS3 were detected by Western blot.RESULTS:Compared with MOD group,serum UA,SCr and BUN levels of the rats in all TFQLM groups were reduced(P<0.05).The XOD and ADA levels in liver tissues were significantly reduced(P<0.05).The protein levels of URAT1,GLUT9,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were decreased(P<0.05),and OAT1 and OAT3 protein expression was increased(P<0.05)in kidneys and HK2 cells.CONCLUSION:By establishing rat and HK2 cell HUA models,it is hypothesized that TFQLM may reduce UA levels and attenuate renal inflammation in HUA rats,and its mechanism may be related to the regulation of UA transport proteins and inhibition of the JAK2/STAT3 signaling pathway.

Objective To analyze the factors influencing iodine nutritional status in pregnant women dur-ing pregnancy,based on thyroid function and thyroid autoantibody levels,and to explore the association between iodine nutritional abnormalities and pregnancy outcomes.Methods A total of 838 pregnant women who underwent routine prenatal checkups at Qinghai Provincial People's Hospital between January 2021 and June 2023 were pro-spectively enrolled in this study.All participants were followed until delivery.Seven cases were lost to follow-up,resulting in a final sample size of 831 participants.Among them,276 were in the first trimester,384 in the second trimester,and 171 in the third trimester.Data on urinary iodine concentration(UIC),urinary creatinine(UCr),thyroid function indicators,and thyroid autoantibodies were collected.Based on their iodine nutritional status,the participants were categorized into either the iodine-sufficient group or the iodine-abnormal group(including iodine-deficient,iodine-hyper-sufficient,and iodine-excessive subgroups).This study analyzed the iodine nutritional sta-tus of pregnant women during different gestational periods,compared thyroid function indices,prevalence of thy-roid diseases,and the positivity rates of thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb),and thyroid-stimulating hormone receptor antibody(TRAb)among different iodine status groups.Additionally,ad-verse pregnancy outcomes were compared across groups.Multivariate logistic regression analysis was conducted to identify risk factors associated with iodine abnormalities during pregnancy,and a predictive model was developed to assess its potential predictive value.Results Among the 831 pregnant women included in the study,373 cases(44.89％)exhibited iodine sufficiency,while 458 cases(55.11％)presented with iodine abnormalities,including 282 cases of iodine deficiency,144 cases of iodine hypersufficiency,and 32 cases of iodine excess.No statistically significant differences were observed in the iodine nutritional status across different trimesters(P>0.05).The se-rum level of thyroid-stimulating hormone(TSH)was significantly higher in the iodine abnormal group compared to the iodine sufficient group(P<0.05).Additionally,the iodine abnormal group demonstrated higher positivity rates of TPOAb alone,TGAb,and TRAb,as well as increased incidence of thyroid dysfunction and total adverse pregnancy outcomes compared to the iodine sufficient group(all P<0.05).These adverse indicators were also sig-nificantly elevated in the iodine-deficient,iodine super-sufficient,and iodine overdose subgroups compared to the iodine sufficient group(P<0.05).Elevated serum TSH levels and the presence of TPOAb,TGAb,and TRAb were identified as risk factors for iodine abnormalities during pregnancy(P<0.05).The predictive model con-structed for identifying iodine abnormalities in pregnant women demonstrated an area under the curve(AUC)of 0.876,with a sensitivity of 72.27％and a specificity of 89.01％.Conclusions The prevalence of iodine nutritional abnormalities among pregnant women during pregnancy was high,with most cases presenting iodine deficiency.These abnormalities were associated with thyroid function,thyroid autoimmunity,and pregnancy outcomes,but showed no significant correlation with gestational age.Furthermore,the prediction model developed based on iden-tified risk factors demonstrated effective performance in predicting iodine nutritional abnormalities during preg-nancy.

Parameters of peripheral blood cell have been shown as the potential predictors of erectile dysfunction (ED). To investigate the clinical significance of hematological parameters for predicting the risk of rapid ejaculation, we established a rat copulatory model on the basis of ejaculation distribution theory. Blood samples from different ejaculatory groups were collected for peripheral blood cell counts and serum serotonin (5-HT) tests. Meanwhile, the relationship between hematological parameters and ejaculatory behaviors was assessed. Final analysis included 11 rapid ejaculators, 10 normal ejaculators, and 10 sluggish ejaculators whose complete data were available. The platelet (PLT) count in rapid ejaculators was significantly lower than that in normal and sluggish ejaculators, whereas the platelet distribution width (PDW) and mean platelet volume (MPV) were significantly greater in rapid ejaculators. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis showed that the PLT was an independent protective factor for rapid ejaculation. Meanwhile, rapid ejaculators were found to have the lowest serum 5-HT compared to normal and sluggish ejaculators ( P < 0.001). Furthermore, there was a positive correlation between the PLT and serum 5-HT ( r = 0.662, P < 0.001), indicating that the PLT could indirectly reflect the serum 5-HT concentration. In addition, we assessed the association between the PLT and ejaculatory parameters. There was a negative correlation between ejaculation frequency (EF) and the PLT ( r = -0.595, P < 0.001), whereas there was a positive correlation between ejaculation latency (EL) and the PLT ( r = 0.740, P < 0.001). This study indicated that the PLT might be a useful and convenient diagnostic marker for predicting the risk of rapid ejaculation.
Male ; Animals ; Ejaculation/physiology* ; Rats ; Platelet Count ; Pilot Projects ; Serotonin/blood* ; Biomarkers/blood* ; Mean Platelet Volume ; Rats, Sprague-Dawley ; ROC Curve ; Erectile Dysfunction/physiopathology*

BackgroundDepression has become a public health concern that affects the physical and mental health of college students. acute stress response is a risk factor of depression. Exploring the relationship and mechanism between acute stress response and depression is of great significance for preventing and intervening depression in college students. ObjectiveTo examine the relationship between acute stress response and depression among college students， and to analyze the mediating role of rumination and the moderated effect of perceived social support， so as to provide references for the prevention and intervention of depression in college student . MethodsFrom March to April 2020， a cluster sampling method was employed to select 1 355 college students from three universities in Hubei， Jiangxi and Guangxi Zhuang Autonomous Region. Participants were assessed with Acute Stress Disorder Scale （ASDS）， Ruminative Responses Scale （RRS）， Brief form of Perceived Social Support Questionnaire （F-SozU） and Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）. Pearson correlation analysis was adopted to examine the correlation between the scores of each scale. The mediating role of rumination between acute stress response and depression and the moderated role of perceived social support were examined respectively by using Model 4 and Model 14 in Macro Program Process 3.3. ResultsA total of 1 303 valid questionnaires were collected， yielding a valid response rate of 96.16%. The results of Pearson correlation analysis showed that ASDS score was positively correlated with RRS score and PHQ-9 score （r=0.649， 0.528， P<0.01） among college students. The mediation analysis results demonstrated that rumination played a partial mediating role between acute stress response and depression， with the mediating effect value of 0.273 （95% CI：0.222~0.328）， accounting for 68.59% of the total effect. Perceived social support played a moderated role in the latter path of the mediation model （rumination → depression） （β=-0.004， 95% CI： -0.017~-0.004， P<0.01）. ConclusionRumination played a partial mediating role between acute stress response and depression in college students， and perceptive social support played a moderated role between rumination and depression. ［Funded by Scientific Research Fund Project of Education Department of Yunnan Province （number， 2025J0437）］