Objective:To discuss the effect of berberine hydrochloride(BBR)on autophagy in the HeLa cells infected with herpes simplex virus type 1(HSV-1),and to clarify its related mechanism.Methods:The HeLa cells at logarithmic growth phase were added with 0,10,20,40,80,120,and 160 μmol·L-1 BBR,respectively,and cultured for 24 h.In addition,the HeLa cells were divided into HSV-1 group(the cells were infected with HSV-1),L-BBR group(were infected with HSV-1 and then treated with 20 μmol·L-1 BBR for 24 h),M-BBR group(were infected with HSV-1 and then treated with 40 μmol·L-1 BBR for 24 h),H-BBR group(were infected with HSV-1 and then treated with 80 μmol·L-1 BBR for 24 h),and 740 Y-P group(were infected with HSV-1 and then treated with 80 μmol·L-1 BBR and 10 μmol·L-1 740 Y-P for 24 h)for viral infection and corresponding drug treatment.MTT method was used to detect the activities of microtubule-associated protein 1 light chain 3(LC3)the HeLa cells after treated with different concentrations of BBR;plaque reduction assay was used to detect the proliferation ability of HSV-1 in the HeLa cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of virus replication-related genes in the HeLa cells in various groups;immunofluorescence method was used to detect the formation of autophagosomes in the HeLa cells in various groups;flow cytometry was used to detect the apoptotic rate of the HeLa cells in various groups;Western blotting method was used to detect the expression levels of autophagy and the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway pathway-related proteins in the HeLa cells in various groups.Results:The MTT method results showed that compared with 0 μmol·L-1 BBR group,the activities of the HeLa cells in 120 and 160 μmol·L-1 BBR groups were significantly decreased(P<0.05),which had certain toxicity to the cells;20,40,and 80 μmol·L-1 BBR were selected for subsequent experiments.The plaque reduction assay results showed that compared with HSV-1 group,the plaque forming units(PFUs)in the HeLa cells in L-BBR group,M-BBR group,and H-BBR group were significantly decreased(P<0.05)in a dose-dependent manner;compared with H-BBR group,the PFUs in the HeLa cells in 740 Y-P group were significantly increased(P<0.05).The RT-qPCR results showed that compared with HSV-1 group,the mRNA expression levels of infected cell protein 0(ICP0),infected cell protein 22(ICP22),infected cell protein 8(ICP8),thymidine kinase(TK),glycoprotein B(gB),and glycoprotein D(gD)in the HeLa cells in L-BBR group,M-BBR group,and H-BBR group were significantly decreased(P<0.05)in a dose-dependent manner;compared with H-BBR group,the expression levels of ICP0,ICP22,ICP8,TK,gB,and gD mRNA in the HeLa cells in 740 Y-P group were significantly increased(P<0.05).The immunofluorescence method results showed that compared with HSV-1 group,the number of LC3 autophagosomes formed in the HeLa cells in L-BBR group,M-BBR group,and H-BBR group was increased;compared with H-BBR group,the number of LC3 autophagosomes formed in the HeLa cells in 740 Y-P group was decreased.The flow cytometry results showed that compared with HSV-1 group,the apoptotic rates of the HeLa cells in L-BBR group,M-BBR group,and H-BBR group were significantly increased(P<0.05)in a dose-dependent manner;compared with H-BBR group,the apoptotic rate of the HeLa cells in 740 Y-P group was significantly decreased(P<0.05).The Western blotting method results showed that compared with HSV-1 group,the expression levels of Beclin-1 and B-cell lymphoma 2(Bcl-2)/adenovirus E1B 19kDa protein interacting protein protein(BNIP)2 proteins and the ratios of LC3-Ⅱ/LC3-Ⅰ in the HeLa cells in L-BBR group,M-BBR group,and H-BBR group were significantly increased(P<0.05)in a dose-dependent manner;compared with H-BBR group,the expression levels of Beclin-1 and BNIP proteins and the LC3-Ⅱ/LC3-Ⅰ ratio in the HeLa cells in 740 Y-P group were significantly decreased(P<0.05);compared with HSV-1 group,the expression levels of cysteine-containing aspartate protein hydrolase 1(Caspase-1),cysteine-containing aspartate protein hydrolase 3(Caspase-3),and Bcl-2 associated X protein(Bax)proteins in the HeLa cells in L-BBR group,M-BBR group,and H-BBR group were significantly increased(P<0.05),and the expression level of Bcl-2 protein was significantly decreased(P<0.05)in a dose-dependent manner;compared with H-BBR group,the expression levels of Caspase-1,Caspase-3,and Bax proteins in the HeLa cells in 740 Y-P group were significantly decreased(P<0.05),and the expression level of Bcl-2 protein was significantly increased(P<0.05);compared with HSV-1 group,the ratios of phosphorylated PI3K(p-PI3K)/PI3K,phosphorylated AKT(p-AKT)/AKT,and phosphorylated mTOR(p-mTOR)/mTOR in the HeLa cells in L-BBR group,M-BBR group,and H-BBR group were significantly decreased(P<0.05)in a dose-dependent manner;compared with H-BBR group,the ratios of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR in the HeLa cells in 740 Y-P group were significantly increased(P<0.05).Conclusion:BBR can promote the autophagy process in the HeLa cells infected with HSV-1 by regulating the PI3K/AKT/mTOR pathway,induce autophagy-dependent apoptosis,and significantly inhibit the virus replication.

Synovium is the target organ of rheumatoid arthritis.The excessive proliferation of synovial cells and insufficient apoptosis lead to synovial hyperplasia,which in turn causes damage to the surrounding tissues of the joint and bone destruction."Yang transforming qi and yin forming elements"is derived from Su Wen and is a highly summarized description of the functions of yin and yang,which runs through the entire course of the disease.This article elucidated the theoretical connotation of"yang transforming qi and yin forming elements"and its connection with synovial hyperplasia,proposing that the insufficiency of"yang transforming qi"is the root of synovial hyperplasia,while the excess of"yin forming elements"is the manifestation of synovial hyperplasia.Based on this,it put forward that"assisting yang qi as the priority,and according to the bias of pathogenic factors of yin,supplementing the method of reducing yin forming elements"is an important principle for treating this disease,which could provide new ideas for the treatment of the disease.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Being a minimally-invasive surgery,the transcatheter arterial embolization treats tumor and vascular diseases mainly through the way of selective endovascular obstruction.Clinically,a variety of embolic agents are available,which include solid embolic agents,liquid embolic agents,and embolic devices.Owing to the consistency of particle size and controllable delivery,the solid embolic agents,especially microspheres-based embolic agents,can effectively achieve the accurate embolization of the tumor blood vessels.Such embolic agents can not only obstruct blood flow but also carry effective anticancer drugs which can be released at the same time of embolization procedure,thus,enhancing the therapeutic effect.Besides,embolic microspheres containing radiopaque components such as iodine,barium,and tantalum,can achieve inherent traceability and monitor the real-time location of embolic agent within body,providing timely information feedback to physicians.As the first part of the topic,this paper makes a comprehensive review about the recent advances in solid embolic agents(focusing on embolic microspheres),aiming to promote the development of this scientific research field.

Being a minimally-invasive procedure,transcatheter arterial embolization can treat tumors and vascular diseases by obstructing the lesion s blood vessels.Embolic agents have been constantly developed so as to meet the requirements in clinical practice.Compared with solid embolic agents,liquid embolic agents and new-type liquid-solid phase conversion type embolic agents have more unique physicochemical properties,which,theoretically,are capable of occluding all the fine vascular branches at the target site.Besides,the microrobot drugs emerging in recent years can be delivered to lesion sites that are difficult to reach in the human body by using multiple external driving sources(such as sound,light,magnetic,etc.),which is of a great advantage in embolization therapy.As the second part of the topic,this paper makes a comprehensive review about the research achievements in embolic equipment,liquid embolic agents and liquid-solid phase conversion type embolic agents,and discusses their characteristics,advantages,clinical application prospects and their shortcomings,aiming to promote the development of this scientific research field.

Objective To evaluate the efficacy and safety of percutaneous vertebroplasty(PVP)using a 17 G puncture needle for the treatment of painful cervical osteolytic metastases.Methods The clinical data of 42 patients with cervical osteolytic metastases(53 lesions in total),who were treated with PVP at the Affiliated Zhongda Hospital of Southeast University of China from March 2012 to March 2024,were retrospectively analyzed.Visual Analog Scale(VAS)was used to evaluate the clinical efficacy and procedure-related complications at one week,one month,3 months,6 months,and one year after PVP.Follow-up CT scan was performed at 1-3 days after PVP so as to evaluate the condition of bone cement filling and leakage.Results Successful PVP using a 17 G puncture needle was accomplished for all the 53 diseased cervical vertebrae.Among them,one patient had one diseased vertebra of C1 and each in 5 patients had one diseased vertebra of C2,and all the 6 lesions were treated with CT-guided PVP;each in 6 patients had one diseased vertebra of C2 and 30 patients had 41 diseased vertebrae of C3-C6,and all the 47 lesions were treated with DSA fluoroscopy-guided PVP.The mean volume of bone cement injected in each vertebra was(1.9±0.45)mL,and the mean bone cement filling rate in each vertebra was(83.5±9.7)％.The preoperative average VAS score was 8.2 points,and it decreased by 5.6,6.1,6.2,5.9,and 5.7 points at one week,one month,3 months,6 months,and one year after PVP,respectively.There was a statistically significant difference in VAS score between one week after PVP and before PVP(P＜0.01),but no statistically significant differences in VAS scores existed within one year after PVP(all P＞0.05).Asymptomatic leakage of bone cement occurred in 14(26.4％)cervical vertebrae.One patient developed pharyngeal infection(adopting the anterior oblique puncture approach),which was cured after anti-infection treatment.No procedure-related complications such as neck bleeding,hematoma,etc.were observed.The lesion control rates at 3,6,and 12 months after PVP were 94.3％,93.9％,and 88.9％,respectively,there was no statistically significant difference in lesion control rates among the follow-up time-points(P=0.580).Conclusion For the treatment of painful cervical osteolytic metastases,PVP using a 17 G puncture needle is clinically safe and feasible.PVP can quickly relieve cervical pain and maintain cervical stability for a long time.Bone cement filling has a good control effect on cervical osteolytic metastatic tumors,although this control effect will decrease over time.

Objective:To investigate the differences and prognostic value of serum myeloid-related proteins 8 and 14 (Mrp 8/14) in patients with acute respiratory distress syndrome (ARDS) induced by pulmonary and extrapulmonary sepsis.Methods:A retrospective cohort study was conducted to collect the general clinical data of septic ARDS patients admitted to the intensive care unit (ICU) of Nanjing Hospital of Nanjing Medical University from August 2021 to February 2024. The serum levels of Mrp 8/14 were detected within 24 hours after admission. According to whether the patients died during ICU stay, the patients with pulmonary ARDS and extrapulmonary ARDS induced by sepsis were divided into survival and death groups, respectively. The differences of Mrp 8/14 and other clinical data between the two groups were compared. Logistic regression analysis was used to analyze the prognostic factors of septic patients with pulmonary ARDS and extrapulmonary ARDS. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of serum Mrp 8/14 for the prognosis of patients with pulmonary ARDS and extrapulmonary ARDS.Results:A total of 138 patients with sepsis-induced ARDS were enrolled in this study, including 79 patients with pulmonary ARDS and 59 patients with extrapulmonary ARDS. Compared to the death group, the level of serum Mrp 8/14 was significantly lower [Mrp 8/14: 22.90 (17.91, 30.88) μg/mL vs. 10.73 (7.15, 17.20) μg/mL, P<0.05]. Multivariate logistic regression analysis demonstrated that the serum Mrp 8/14 level was an independent risk factor for the prognosis of pulmonary ARDS patients only during the ICU stay ( OR=1.253, 95% CI: 1.110-1.414, P<0.05). ROC curve analysis showed that the area under the curve of serum Mrp 8/14 for the prediction of death in ARDS patients with pulmonary sepsis during ICU stay was 0.855 (95% CI: 0.773-0.938, P<0.05), the cut-off value was 19.230 μg/mL, the sensitivity was 0.718, the specificity was 0.925, and the Yonden index was 0.405. Conclusion:Serum Mrp 8/14 is an effective prognostic indicator for the mortality of ARDS patients with pulmonary sepsis during ICU hospitalization.

Objective To explore the correlation between serum vitamin D(VD3)level differences and immune inflammatory markers in elderly sepsis patients.Methods A total of 103 elderly patients with sepsis(aged 65-99 years)in the ICU of the First Affiliated Hospital of Kunming Medical University from January 2020 to December 2022 were collected and divided into two groups according to the diagnostic criteria for VD3 deficiency:VD3 deficiency group(n=32)and VD3 severe deficiency group(n=71).Correlation analysis was conducted by comparing the differences in serum 25-(OH)-D3(VD3)levels,immune function-related indicators upon admission(blood routine,infection-related proteins,combined detection of 12 cytokines,absolute count analysis of lymphocytes and subgroups,quantitative determination of infection-related immune cells,immunoglobulin,and complement),illness severity,and prognostic indicators(APACHE-II score,SOFA score,duration of ICU stay,and 28-day mortality rate).Result(1)Serum VD3 levels were lower in elderly patients with sepsis.No patient was in the VD3 normal or insufficient group.Patients with severe VD3 deficiency had higher APACHE-II scores,SOFA scores,and 28-day mortality rates than those with VD3 deficiency,and these scores were negatively correlated with serum VD3 levels(P<0.001),while the difference in ICU stay duration between the two groups was not statistically significant(P>0.05);(2)WBC,PCT,CRP,and CD4/CD8 in the VD3 deficiency group were all lower than those in the VD3 severe deficiency group(P<0.05),while IL-6,IL-10,CD45+,CD3+/CD45+,and CD19+Abs were all higher than those in the VD3 severe deficiency group(P<0.05);In the VD3 deficiency group,VD3 levels were positively correlated with CD45+(P<0.05 for all),while negatively correlated with IL-6,IL-10,PCT,and CRP(P<0.05 for all);In the VD3 severe deficiency group,there were fewer corre-lation indicators and the correlation strength was not as strong as that in the VD3 deficiency group.Conclusion(1)Elderly patients with sepsis generally have lower levels of VD3,with lower levels associated with more severe illness and poorer prognosis;(2)In elderly sepsis patients,compared to patients with severe VD3 deficiency,patients with VD3 deficiency have lower levels of inflammation,stronger cellular immune response,and stronger correlation,suggesting that the effects of different VD3 levels on immune inflammatory responses may vary in elderly sepsis patients.

Objective:To investigate the dynamic imaging characteristics of hepatocellular carcinoma (HCC) following Yttrium-90 selective internal radiation therapy ( 90Y-SIRT) and to compare these with imaging findings after transarterial chemoembolization (TACE). Methods:This retrospective case-control study included 24 HCC patients who received 90Y-SIRT at Zhongda Hospital, Southeast University, and West China Hospital, Sichuan University, between September 2021 and June 2023, establishing the 90Y-SIRT group. Additionally, 45 HCC patients who underwent their first TACE treatment at Zhongda Hospital, Southeast University during the same period were included as the TACE group. Patients underwent MRI and/or CT follow-ups at 1-3 months (first follow-up) and 3-6 months (second follow-up) after treatment. The analyzed imaging features included tumor characteristics, peritumoral features, and measurements of tumor and liver volumes, with postoperative change rates calculated. Imaging differences between the 90Y-SIRT and TACE groups were statistically compared using the Mann-Whitney U test or χ2 test. Results:At the first follow-up, compared to baseline, a higher proportion of lesions in the 90Y-SIRT group exhibited a reduction in arterial phase enhancement in the viable region (10/13) than in the TACE group (10/29), with a statistically significant difference ( P=0.040). The necrotic region of the tumor on T 1WI showed significantly lower signal intensity in the 90Y-SIRT group than in the TACE group ( Z=2.98, P=0.006). The change in the apparent diffusion coefficient value in the viable region compared to baseline was 157.0×10 -3(-62.0×10 -3, 311.5×10 -3) mm2/s in the 90Y-SIRT group and -56.0×10 -3 (-216.8×10 -3, 110.0×10 -3) mm2/s in the TACE group, with a statistically significant difference ( Z=-2.71, P=0.008). At the first and second follow-up, the contralateral liver lobe volume increased significantly in the 90Y-SIRT group, with a statistically significant difference from the TACE group ( Z=-3.21, -3.78, both P=0.001). Regarding peritumoral imaging characteristics, a statistically significant difference was observed between the two groups in the low signal intensity of the liver lobe or segment where the tumor waslocated during the hepatobiliary phase ( P=0.020, 0.040). Both HCC groups exhibited progressive tumor volume reduction after treatment. In the 90Y-SIRT group, the change rates of lesion volume relative to baseline at the two follow-ups were -23.0% (-45.6%, 7.9%) and -68.7% (-82.7%, -28.5%), respectively. In the TACE group, the values were -29.8% (-53.6%, -2.7%) and -38.0% (-65.3%, -10.7%). The differences between the two groups were not statistically significant ( Z=-0.52, P=0.605; Z=-1.79, P=0.073). Conclusion:There is a statistically significant difference in the tumor imaging features and peritumoral imaging characteristics between 90Y-SIRT and TACE. 90Y-SIRT demonstrates a notable advantage in promoting contralateral liver lobe regeneration while also contributing to tumor size reduction.

Objective:To investigate the effect of repetitive transcranial magnetic stimulation(rTMS)on sleep structure and quality in children with autism spectrum disorder(ASD).Methods:Sixty children with ASD who met the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)criteria were randomly assigned to rTMS treatment group and pseudo-treatment group.The rTMS group received bilateral low-frequency(0.5 Hz)stimulation,and the pseudo-treatment group received pseudo-stimulation at the same time and place.Sleep quality and autism symptoms were assessed at baseline,midpoint(15 sessions),and endpoint(30 sessions),using the Childhood Sleep Disorders Scale(SDSC)and the Behavior Rating Scale for Children with Autism Spectrum Disorders(ABC)before treatment,15 times and 30 times of intervention,and statistical analysis was performed.Results:There was no significant difference in SDSC factor and total score between the two groups before treatment(P＞0.05).After 15 and 30 treatments,the total scores of SDSC and all factors were lower in the rTMS group than in the pseudo-treatment group(P＜0.05).Repeated measurement ANOVA found that there was an interaction be-tween the groups and the number of interventions,that is,the scores of the two groups had different downward trends,and the decline of the treatment group was more obvious than that of the pseudo-treatment group.There was no significant difference in the interaction between ABC scale scores and intervention times(P＞0.05).Conclu-sion:Repetitive transcranial magnetic stimulation significantly improves the sleep structure and quality in children with autism spectrum disorder.