Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Premature ovarian insufficiency （POI） is a reproductive endocrine disorder that severely affects female reproductive health. However， there remains a lack of clinically effective and safe therapeutic options to restore ovarian function. Traditional Chinese medicine （TCM）， with its advantages of multi-component and multi-target holistic regulation， has shown unique potential in the prevention and treatment of POI. Among TCM monomers， curcumin， resveratrol， and icariin exert antioxidant， anti-inflammatory， and anti-ovarian granulosa cell apoptosis effects by regulating signaling pathways such as nuclear factor-erythroid 2-related factor 2/heme oxygenase-1， phosphoinositide 3-kinase/protein kinase B， and mitogen-activated protein kinase. Single TCM herbs， including American ginseng， Cuscutae Semen， and Cistanches Herba， can regulate sex hormone levels， and alleviate ovarian oxidative stress and immune damage. TCM compound formulas such as Yijing decoction， Siwu decoction， Zuogui pill， and Kuntai capsule modulate multiple signaling pathways， including vascular endothelial growth factor/vascular endothelial growth factor receptor-2， phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin， and silence information regulator 1/p53， thereby promoting angiogenesis， inhibiting mitochondrial apoptosis， and regulating autophagy and ferroptosis， which ultimately delay follicular atresia and improve ovarian reserve function. Further studies are suggested to apply artificial intelligence to deeply explore the underlying mechanisms and carry out high-quality clinical trials， so as to promote the standardized application of TCM in the prevention and treatment of POI.

Objective:To explore clinical characteristics of multiple sclerosis(MS)patients in Suzhou,and to analyze main factors affecting their prognosis.Methods:General data,clinical symptoms,cerebrospinal fluid and imaging examinations of 51 MS patients admitted to Department of Neurology of the Second Hospital of Soochow University from July 31,2009 to July 31,2021 were retrospectively analyzed,and main factors affecting their prognosis were discussed.Results:Average age of onset of 51 MS patients was(43.3±15.6)years old,female accounted for 56.9%,male/female=1/1.3.Adult onset MS(AOMS)accounted for 62.8%,male/female=1/1.7;late onset MS(LOMS)accounted for 37.2%,male/female=1/0.9.Relapsing remitting MS(RRMS)accounted for 76.5%,and chronic onset accounted for 60.8%.Average annual recurrence rate was 8.8%.The first symptoms were numbness and weakness of limbs.Dizziness and numbness were more common in patients without recurrence after diagnosis of MS,and limb weak-ness and numbness were more common in patients with recurrence.Among lesions of MRI,62.7%(32/51)of periventricular involve-ment,52.9%(27/51)of spinal cord involvement,51.0%(26/51)of infratentorial involvement.Proportion of subtentorial and spinal cord(cervical,thoracic)involved were significantly higher in patients with recurrent MS than without recurrence.Values of albumin,IgG,IgA and IgM in cerebrospinal fluid increased with increase of recurrence times.EDSS score of male was higher than female,and LOMS score was higher than AOMS.MS patients without relapse had a low EDSS score,and median EDSS score at current follow-up was 0(0,1.00)score.MS score with relapse was relatively high,and median EDSS score at current follow-up was 2.75(0.25,7.25)score.Conclusion:MS patients with chronic onset are more common,with a high proportion of LOMS,and proportion of males increases with increasing age of onset.High EDSS score at first onset,cervical,thoracic and subtentorial lesions,increased values of cerebrospinal fluid albumin,IgG,IgA,IgM,age at first onset(50+years old),male associate with poor MS prognosis.

Objective To explore the feasibility of treating recurrent mandibular neuralgia with radiofrequency thermocoagulation with double needle guide,and to study the clinical value of double needle puncture for foramen ovale.Methods In this study,40 patients with recurrent mandibular neuralgia admitted to our hospital from January 2018 to November 2023 were selected,and randomly divided into the observation group(20 cases using double-needle guide technology)and control group(20 cases using traditional single-needle guide technology).The two groups were compared before and after treatment.Results After the completion of radiofrequency thermo-coagulation therapy,the overall pain-free rate of all cases was 90％according to the adjusted grading criteria,and there was a differ-ence in the pain-free rate between the two groups(P＜0.05).There was no significant difference in the number of puncture adjustment and complications between the two groups(P＞0.05).The operation time of the observation group was longer than that of the control group(P＜0.05),and the number of postoperative acupuncture pain cases was statistically different from that of the control group(P＜0.05).After comparison of facial visual analogue scale(F-VAS),it was found that there were significant differences between the two groups(P＜0.05),and there were statistical differences between the observation group and the control group(P＜0.05).Conclusion Radiofrequency thermocoagulation with double-channel technique treating patients with recurrent mandibular neuralgia is,more thorough and has less complications.Although the operation time is increased,it can effectively eliminate the pain of patients.The tra-ditional bipolar radiofrequency thermocoagulation therapy technology is easily and accurately accomplished,which is worth popularizing.

OBJECTIVE To explore the potential mechanism of Yiqi Wenyang Recipe in the intervention of allergic rhinitis(AR)mice.METHODS C57/BL6 mice were randomly divided into blank,model,Yiqi Wenyang Recipe and Yiqi Wenyang Recipe+EX-527[Sirtuin 1(SIRT1)inhibitor]groups.The AR model of mice was established by ovalbumin based challenge sensitization method,each group received corresponding intervention measures.Assessment of behavioral changes in mice;nasal mucosal lesions were observed by HE and toluidine blue staining;the serum levels of interleukin-4(IL-4),interferon-γ(IFN-γ),and immunoglobulin E(IgE)were measured by ELISA;the expression levels of phospho-Janus kinase 2(p-JAK2),phospho-signal transducer and activator of transcription 6(p-STAT6),phospho-dynamin-related protein 1(p-Drp1),SIRT1,peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)in nasal mucosa were determined by Western blot combined with immunofluorescence;reactive oxygen species(ROS)levels were detected by fluorescent probe method;the morphological changes of mitochondria in the microstructure of na-sal mucosa were observed by transmission electron microscopy.RESULTS Compared with the blank group,the frequency of scratch-ing and sneezing in the model group was significantly increased,and a large number of eosinophils and mast cells were found in the na-sal mucosa(P<0.05);compared with the model group,the nasal allergic symptoms and the level of nasal mucosal inflammatory reaction in the Yiqi Wenyang Recipe group were significantly improved(P<0.05);compared with the Yiqi Wenyang Recipe group,the scratch-ing and sneezing of mice in the Yiqi Wenyang Recipe+EX-527 group increased again,and the counts of eosinophils and mast cells in nasal mucosa increased significantly(P<0.05).Compared with the model group,the levels of serum IL-4 and IgE in the Yiqi Wenyang Recipe group decreased,while the level of serum IFN-γ increased(P<0.05);the serum IL-4 and IgE of mice in the Yiqi Wenyang Recipe+ex-527 group were significantly higher than those in the Yiqi Wenyang Recipe group(P<0.05).Western blot and immunofluo-rescence showed that Yiqi Wenyang Recipe could effectively inhibit the increase of p-JAK2,p-STAT6,p-Drp1(ser616)levels induced by ovalbumin sensitization,as well as the decrease of SIRT1 and PGC-1 α expression(P<0.01);however,the intervention of EX-527 significantly blunted the regulatory effect of Yiqi Wenyang Recipe on the above signaling molecules(P<0.05,P<0.01).The results of transmission electron microscopy and fluorescent probe showed that in the model group,a large number of spherical mitochondria were found in the mitochondria of nasal mucosa,and the level of ROS was significantly increased(P<0.01);;the intervention of Yiqi We-nyang recipe effectively restored the long tubular morphology of mitochondria and reduced ROS level(P<0.01);,while the intervention of EX-527 weakened the above improvement effect(P<0.01).CONCLUSION Yiqi Wenyang Recipe can regulate SIRT1 to activate PGC-1α,and then inhibit Drp1 mediated excessive mitochondrial fission to intervene AR;SIRT1 may be one of the important targets of Yiqi Wenyang Recipe in the intervention of AR.

The incidence of chronic venous disease(CVD)is significantly higher in the elderly population compared to non-elderly individuals,with more severe disease manifestations.Additionally,elderly CVD patients often have comorbid conditions such as cardiovascular diseases,making the evaluation process more complex and increasing treatment difficulty.Currently,there are no established recommendations in China for the diagnosis and treatment of CVD in individuals aged 60 and above.Against this backdrop,the Peripheral Vascular Disease Management Branch of the Chinese Geriatric Society has developed the Chinese Expert Consensus on the Diagnosis and Treatment of Chronic Venous Disease in the Elderly based on domestic and international guidelines,relevant evidence-based medical research,and the physiological and clinical characteristics of the elderly population in China.This consensus aims to provide an important reference for improving the diagnosis and treatment of CVD in elderly patients in China.

OBJECTIVE To explore the potential mechanism of Yiqi Wenyang Recipe in the intervention of allergic rhinitis(AR)mice.METHODS C57/BL6 mice were randomly divided into blank,model,Yiqi Wenyang Recipe and Yiqi Wenyang Recipe+EX-527[Sirtuin 1(SIRT1)inhibitor]groups.The AR model of mice was established by ovalbumin based challenge sensitization method,each group received corresponding intervention measures.Assessment of behavioral changes in mice;nasal mucosal lesions were observed by HE and toluidine blue staining;the serum levels of interleukin-4(IL-4),interferon-γ(IFN-γ),and immunoglobulin E(IgE)were measured by ELISA;the expression levels of phospho-Janus kinase 2(p-JAK2),phospho-signal transducer and activator of transcription 6(p-STAT6),phospho-dynamin-related protein 1(p-Drp1),SIRT1,peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)in nasal mucosa were determined by Western blot combined with immunofluorescence;reactive oxygen species(ROS)levels were detected by fluorescent probe method;the morphological changes of mitochondria in the microstructure of na-sal mucosa were observed by transmission electron microscopy.RESULTS Compared with the blank group,the frequency of scratch-ing and sneezing in the model group was significantly increased,and a large number of eosinophils and mast cells were found in the na-sal mucosa(P<0.05);compared with the model group,the nasal allergic symptoms and the level of nasal mucosal inflammatory reaction in the Yiqi Wenyang Recipe group were significantly improved(P<0.05);compared with the Yiqi Wenyang Recipe group,the scratch-ing and sneezing of mice in the Yiqi Wenyang Recipe+EX-527 group increased again,and the counts of eosinophils and mast cells in nasal mucosa increased significantly(P<0.05).Compared with the model group,the levels of serum IL-4 and IgE in the Yiqi Wenyang Recipe group decreased,while the level of serum IFN-γ increased(P<0.05);the serum IL-4 and IgE of mice in the Yiqi Wenyang Recipe+ex-527 group were significantly higher than those in the Yiqi Wenyang Recipe group(P<0.05).Western blot and immunofluo-rescence showed that Yiqi Wenyang Recipe could effectively inhibit the increase of p-JAK2,p-STAT6,p-Drp1(ser616)levels induced by ovalbumin sensitization,as well as the decrease of SIRT1 and PGC-1 α expression(P<0.01);however,the intervention of EX-527 significantly blunted the regulatory effect of Yiqi Wenyang Recipe on the above signaling molecules(P<0.05,P<0.01).The results of transmission electron microscopy and fluorescent probe showed that in the model group,a large number of spherical mitochondria were found in the mitochondria of nasal mucosa,and the level of ROS was significantly increased(P<0.01);;the intervention of Yiqi We-nyang recipe effectively restored the long tubular morphology of mitochondria and reduced ROS level(P<0.01);,while the intervention of EX-527 weakened the above improvement effect(P<0.01).CONCLUSION Yiqi Wenyang Recipe can regulate SIRT1 to activate PGC-1α,and then inhibit Drp1 mediated excessive mitochondrial fission to intervene AR;SIRT1 may be one of the important targets of Yiqi Wenyang Recipe in the intervention of AR.

Wastewater-based epidemiology(WBE)has emerged in recent years as a crucial complementary tool for tracking the community transmission and infection prevalence of SARS-CoV-2 and other viral pathogens.This short review comprehensively de-scribes the diversity of viruses in wastewater,with a focus on current advancements in aspects including sampling methods,concentra-tion and enrichment strategies,detection approaches,and setting up quality controls for wastewater-based viral pathogen surveillance.The systematic summary of global status,technical progress,and challenges highlights the feasibility of WBE viral surveillance within a One Health framework,thus facilitating use of WBE as a tool for early warning of viral disease outbreaks and predicting epidemic trends in the future.

The ribosomal protein S11(RPS11)from Enterococcus faecalis is was heterologously ex-pressed using the Pichia pastoris system.The RPS11 gene sequence was optimized to match the yeast codon preference,and the recombinant expression vector pPIC9K-RPS11 was constructed.Electroporation was used to transform the vector into the Pichia pastoris GS115 strain,and high-copy recombinant strains were selected through G418 resistance screening.Protein expression was induced with methanol,and the expression was verified by SDS-PAGE.The recombinant protein was applied in a mouse melanoma treatment model to evaluate its therapeutic effects.The results showed that the recombinant expression vector pPIC9K-RPS11 successfully expressed the target protein with an approximate molecular weight of 14 kDa in Pichia pastoris.The optimal fermenta-tion conditions were determined to be an induction temperature of 30 ℃,induction time of 72 h,and methanol concentration of 1％.Analysis using a mouse peritoneal macrophage trained immuni-ty model revealed that recombinant RPS11 possessed biological activity capable of inducing trained immunity.Additionally,therapeutic experiments in a mouse melanoma model demonstrated that recombinant RPS11 significantly inhibited tumor growth.These findings suggest that the recombi-nant RPS11 secreted by Pichia pastoris not only possesses biological activity in inducing trained immunity but also inhibits tumor cell growth in a mouse melanoma model,providing theoretical support for the heterologous expression and potential applications of recombinant RPS11.

Object·To explore the effects of comorbid obsessive-compulsive personality disorder(OCPD)on the behavioral inhibition system(BIS)/behavioral activation system(BAS)in patients with obsessive-compulsive disorder(OCD).Methods·A total of 247 patients with unmedicated OCD diagnosed in the Mental Health Center,Shanghai Jiao Tong University School of Medicine from 2014 to 2018 were included and divided into an OCD group(n=202),and an OCD+OCPD group(n=45),and 107 healthy controls were recruited as a comparison group.Yale-Brown Obsessive-Compulsion Scale(YBOCS),BIS/BAS Scale,Hamilton Depression Scale(HAMD),and Hamilton Anxiety Scale(HAMA)were used to assess psychopathological features.Gender differences among the three groups were analyzed using the x2 test.One-way analysis of variance(ANOVA)was used to compare differences in demographic characteristics,psychopathological features,and BIS/BAS scores,followed by the least significant difference(LSD)test for pairwise comparisons.Regression analysis was conducted to explore the relationships between psychopathological features and BIS/BAS scores.Results·There were no significant differences in gender,age,and years of education among the three groups.The scores of YBOCS(t=2.925,P=0.004),HAMD(t=2.130,P=0.034)and HAMA(t=2.568,P=0.011)in the OCD+OCPD group were significantly higher than those in the OCD group.There were statistically significant differences in BIS and BAS scores among the three groups(BIS:F=39.573,P＜0.001;BAS:F=3.915,P=0.021).The results showed that for BIS,there were statistically significant differences in pairwise comparisons among the three groups(OCD+OCPD vs OCD:P=0.002;OCD+OCPD vs HC:P＜0.001;OCD vs HC:P＜0.001),and the scores were OCD+OCPD＜OCD＜HC from low to high.For BAS,the OCD group scored significantly higher than the OCD+OCPD and HC groups(OCD+OCPD vs OCD:P=0.018;OCD vs HC:P=0.043),but there was no significant difference between the OCD+OCPD and HC groups.Regression models of BIS and BAS were constructed for OCD patients with OCPD,and the results showed that the overall prediction effect of the model was significant for BIS total scores(F=2.599,P=0.013).Only the severity of OCPD symptoms can significantly predict BIS scores(t=-2.282,P=0.023).For BAS total scores,the overall prediction effect of the model was not significant(F=1.438,P=0.191).Conclusion·Comorbid OCPD may be an adverse factor for abnormal BIS and a protective factor for abnormal BAS in patients with OCD.