Hepatitis B virus （HBV） infection is one of the major global health problems， and it can lead to the development of liver cirrhosis and hepatocellular carcinoma. Due to the strict species specificity of HBV infection， no animal model has yet been established to fully support the complete life cycle of HBV infection and accurately reflect host immune responses and pathogenesis. Current animal models used for HBV research include various hosts such as chimpanzees， tree shrews， and mice， as well as surrogate models based on related hepatotropic viruses. Although these models have contributed significantly to the research on HBV replication， immune response， and antiviral drug evaluation， they still have certain limitations such as ethical concerns， low infection efficiency， high costs， and a lack of persistent infection. In recent years， the development of novel strategies， such as humanized mouse models with reconstituted human liver and immune systems， transgenic models， and viral vector-mediated infection systems， has greatly promoted the research on HBV biology. In the future， with the integration of emerging technologies including gene editing， tissue engineering， and multi-system reconstruction， it is possible to establish HBV infection models that can more closely mimic human pathophysiology， thereby laying a robust foundation for understanding virus-host interactions， exploring the pathways for viral clearance， and developing radical treatment strategies.

ObjectiveTo investigate the possible mechanism of Shenfuhuang Formula （参附黄配方） in prevention and treatment of epsis-associated encephalopathy from the perspective of brain genomics. MethodsC57BL/6 mice were randomly divided into sham surgery group， sepsis group， and Shenfuhuang group， with 20 mice in each group. The sepsis group and Shenfuhuang group were induced to develop sepsis by cecal ligation and puncture （CLP） procedure. At 4 hours after modelling， Shenfuhuang group were gavaged with 2.5 g/（kg·d） of Shenfuhuang Formula， 0.5 ml each time， at 12 hours intervals， for a total of 4 times after modelling. Sepsis group and sham surgery group were given 0.5 ml of purified water orally. At 48 hours after modeling， the transcriptome sequencing was used to explore the differential gene expression in the effects of Shenfuhuang Formula on the brain regions of septic mice， and real-time PCR and ELISA were later used to further validate the differential gene and proteins expression. ResultsA total of 4605 genes were differentially expressed in Shenfuhuang group compared with sepsis group， of which 2353 genes were up-regulated and 2252 genes were down-regulated. According to the results of previous publications， six key genes were screened， including serine/threonine-protein kinase （Nek1）， myelin-associated glycoprotein （Mag）， endothelial cell-specific tyrosine kinase receptor （Tek）， a disintegrin and metalloproteinase with thrombospondin motifs 20 （Adamts20）， lymphocyte antigen 86 （Ly86）， and E3 ubiquitin-protein ligase （Traip）. Further genetic and protein validation revealed that， compared to the sham surgery group， the mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip in the brain tissue of septic mice significantly reduced （P＜0.05）. In comparison to the sepsis group， Shenfuhuang group showed significantly increased mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip （P＜0.05）. ConclusionThe potential therapeutic targets of Shenfuhuang Formula for treating sepsis-associated encephalopathy may be related to the Nek1， Mag， Tek， Adamts20， Ly86， and Traip genes and their encoded proteins.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

OBJECTIVE: To compare the effectiveness of posterior axillary edge approach and arthroscopic assisted reduction in the treatment of Ideberg type Ⅰ and Ⅱ glenoid fracture of the scapula. METHODS: The clinical data of 26 patients with fresh Ideberg type Ⅰ and Ⅱ scapular fractures admitted between June 2021 and September 2024 who met the selection criteria were analyzed retrospectively. The patients were divided into two groups according to different treatment methods. Ten cases in the posterior axillary edge group were fixed by open reduction plate through the posterior axillary edge approach, and 16 cases in the arthroscopy group were treated with suture anchor fixation under arthroscopy. There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, surgical side, Ideberg type, cause of injury, time from injury to operation, rotator cuff injury, and superior labrum anterior posterior (SLAP) injury, etc. The operation time and fracture healing time were recorded and compared between the two groups, and the shoulder pain was evaluated by visual analogue scale (VAS) score at 1 week, 1 month, and 3 months after operation. At 3 and 6 months after operation, the range of motion of shoulder joint in anteflexion, abduction, external rotation, internal rotation, and backward extension was evaluated, the upper limb dysfunction was evaluated by the Disability Assessment Scale of Arm, Shoulder, and Hand (DASH), and the shoulder joint function was evaluated by the Constant-Murley score. The differences between 6 months and 3 months after operation (changes) were statistically analyzed. RESULTS: Patients in both groups were followed up 11-13 months, with an average of 12.5 months. The operation time and fracture healing time in the posterior axillary edge group were significantly shorter than those in the arthroscopy group ( P<0.05). There was no complication such as wound infection, vascular and nerve injury, loss of reduction, bone nonunion, or glenohumeral instability in both groups. At 1 week after operation, the VAS score in the posterior axillary edge group was significantly higher than that in the arthroscopy group ( P<0.05); there was no significant difference in the VAS score between the two groups at 1 and 3 months after operation ( P>0.05). At 6 months after operation, the changes of shoulder joint in anteflexion, internal rotation range of motion and DASH scores in the posterior axillary edge group were significantly lower than those in the arthroscopy group ( P<0.05), while the changes of abduction, external rotation, backward extension range of motion and Constant-Murley scores were not significantly different between the two groups ( P>0.05). CONCLUSION For Ideberg type Ⅰ and Ⅱ glenoid fracture of the scapula, the posterior axillary edge approach for internal fixation has a short operation time, fast fracture healing, and is beneficial for early functional recovery; arthroscopic assisted reduction has minimal trauma and can handle joint injuries simultaneously. Both surgical procedures are safe and effective, and individualized selection should be made based on soft tissue conditions and combined injuries.
Humans ; Arthroscopy/methods* ; Scapula/surgery* ; Male ; Female ; Retrospective Studies ; Adult ; Fracture Fixation, Internal/instrumentation* ; Fractures, Bone/surgery* ; Middle Aged ; Treatment Outcome ; Bone Plates ; Suture Anchors ; Fracture Healing ; Range of Motion, Articular ; Young Adult ; Shoulder Joint/surgery* ; Operative Time

OBJECTIVE: To evaluate the early effectiveness of transosseous suture fixation in treating recurrent acute patellar dislocation with patellar osteochondral fractures (OCFs). METHODS: A retrospective analysis was conducted on 19 patients with recurrent acute patellar dislocation and patellar OCFs, who underwent transosseous suture fixation between January 2018 and December 2022 and were followed up 2 years. The cohort included 8 males and 11 females, aged 13-21 years (mean, 16.2 years). Patients experienced 2-5 times of patellar dislocation (mean, 3.2 times). The interval from the last dislocation to operation ranged from 3 to 15 days (mean, 9.6 days). Preoperative imaging revealed the intra-articular osteochondral fragments and medial patellofemoral ligament (MPFL) injury. Clinical outcomes were evaluated using the visual analogue scale (VAS) score for pain, the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) knee score, the Lysholm score, and the Tegner score. Postoperative complications were recorded. During follow-up, the knee X-ray films, CT, and MRI were taken to evaluate fragment healing, displacement, and the morphology and tension of the MPFL reconstruction graft. RESULTS: All incisions healed primarily, and no complication occurred such as infection, joint stiffness, patellofemoral arthritis, or redislocation. Patients were followed up 24-60 months (mean, 43.5 months). At 12 months postoperatively and the last follow-up, significant improvements ( P<0.05) were observed in VAS, Lysholm, IKDC, HSS, and Tegner scores compared to preoperative values. Further improvements were observed at last follow-up compared with the 12 months postoperatively, and the differences were significant ( P<0.05). Imaging studies demonstrated satisfactory osteochondral fragment positioning with stable fixation. At last follow-up, all fragments had healed, and MPFL reconstruction grafts exhibited optimal morphology and tension. No joint adhesion or fragment displacement occurred. CONCLUSION For recurrent acute patellar dislocation with patellar OCFs, transosseous suture fixation proves to be both safe and effective, achieving satisfactory early effectiveness.
Humans ; Male ; Female ; Patellar Dislocation/surgery* ; Adolescent ; Young Adult ; Retrospective Studies ; Patella/surgery* ; Suture Techniques ; Treatment Outcome ; Recurrence ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; Follow-Up Studies

Systemic lupus erythematosus （SLE） may lead to secondary gynecological and obstetric disorders such as decreased ovarian reserve function， menstrual abnormalities， and adverse pregnancy outcomes. Based on "bi （痹） of both body and viscera" theory， this paper proposed that the core mechanism of SLE secondary gynecological and obstetric diseases lies in the mutual transformation between "body bi" and "viscera bi"， which together affect the uterus. Physiologically， uterus forms an internal-external network with the body and viscera through the meridians and blood vessels. Pathologically， when the healthy qi is deficient， nourishment of the body and viscera is impaired； when toxins and stasis accumulate， pathogenic factors disturb the uterus through the chong （冲） and ren （任） meri-dians. The resulting obstruction in the uterus can， in turn， manifest externally and aggravate damage to the body and viscera. Therefore， the pathogenesis of SLE secondary gynecological and obstetric diseases follows a dynamic trajectory of "body bi first， body bi affecting viscera， and then bi of both body and viscera". In treatment， the principle of harmonizing and balancing the healthy qi is emphasized. The main approach is to regulate the viscera， stabilize the body， and nourish the uterus， with the coordination of nourishing the viscera through the body， thereby achieving simultaneous treatment of both body and viscera. This highlights the guiding significance of the "bi of both body and viscera" theory in preventing and treating SLE secondary gynecological and obstetric diseases.

Objective To investigate the feasibility and clinical experience of kidney transplantation from donors with Marfan syndrome (MFS). Methods Clinical data of 2 recipients undergoing kidney transplantation from the same MFS patient were retrospectively analyzed and literature review of 2 cases was conducted. Characteristics and clinical diagnosis and treatment of kidney transplantation from MFS patients were summarized. Results The Remuzzi scores of the left and right donor kidneys of the MFS patient during time-zero biopsy were 1 and 2. No significant difference was observed in the renal arteriole wall compared with other donors of brain death and cardiac death. Two recipients who received kidney transplantation from the MFS patient suffered from postoperative delayed graft function. After short-term hemodialysis, the graft function of the recipients received the left and right kidney began to gradually recover at postoperative 10 d and 20 d. After discharge, serum creatinine level of the recipient received the left kidney was ranged from 80 to 90 μmol/L, whereas that of the recipient received the right kidney kept declining, and the lowest serum creatinine level was 232 μmol/L before the submission date (at postoperative 43 d). Through literature review, two cases successfully undergoing kidney transplantation from the same MFS donor were reported. Both two recipients experienced delayed graft function, and then renal function was restored to normal. Until the publication date, 1 recipient has survived for 6 years, and the other recipient died of de novo cerebrovascular disease at postoperative 2 years. Conclusions MFS patients may serve as an acceptable source of kidney donors. However, the willingness and general conditions of the recipients should be carefully evaluated before kidney transplantation. Intraoperatively, potential risk of tear of renal arterial media should be properly treated. Extensive attention should be paid to the incidence of postoperative complications.

Objective To investigate the expression of serum Sestrin2 and Toll-like receptor 7(TLR7)in patients with severe pneumonia and sepsis and their predictive value for heart failure.Methods A total of 86 patients with severe pneumonia and sepsis complicated with heart failure(complicated with heart failure group)and 86 patients with severe pneumonia and sepsis(uncomplicated with heart failure group)who were diagnosed and treated in Shanxi Provincial People's Hospital from February 2022 to May 2023 were studied.Another 86 patients who underwent health examinations were included as the control group.Enzyme linked immunosorbent assay(ELISA)method was applied to measure serum levels of Sestrin2 and TLR7.Color doppler echocardiography was applied to measure cardiac function related indicators:left ventricular ejection fraction(LVEF),left ventricular end diastolic diameter(LVEDD),and left ventricular end systolic diameter(LESD).The expression of Sestrin2 and TLR7 levels and cardiac function in three groups was analyzed.Pearson correlation was applied to analyze the relationship between serum levels of Sestrin2 and TLR7 and cardiac function related indicators in patients with heart failure.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum levels of Sestrin2 and TLR7 in patients with severe pneumonia and sepsis complicated with heart failure.Results The serum levels of Sestrin2(11.59±3.31 ng/ml,16.13±3.62 ng/ml),TLR7(48.93±9.52 ng/ml,61.74±10.11 ng/ml),and cardiac function related indicators[LVEDD(53.28±5.76 mm,62.54±6.11 mm)and LESD(38.16±4.38 mm,48.15±5.02 mm)]were higher in uncomplicated heart failure group and complicated heart failure group than those in control group(7.11±2.34 ng/ml,40.12±10.16 ng/ml,44.86±5.02 mm,29.02±4.07 mm),with significant differences(qSestrin2=13.241,26.659,qTLR7=8.224,20.182,qLVEDD=13.824,29.028,qLESD=18.805,39.359,all P＜0.05),and those values in complicated with heart failure group were higher than those in uncomplicated with heart failure group,with significant differences(q=13.418,11.985,15.203,20.554,all P＜0.05).The LVEF(55.43％±6.62％,41.67％±5.84％)index in uncomplicated heart failure group and complicated heart failure group was lower than that in control group(62.75％±7.16％),with significant differences(q=10.344,29.789,all P＜0.05),and the index in complicated with heart failure group was lower than that in uncomplicated with heart failure group,with significant difference(q=19.455,P＜0.05).Pearson correlation analysis showed that serum levels of Sestrin2 and TLR7 in patients with heart failure were negatively correlated with LVEF(r=-0.419,-0.467,all P＜0.05),and positively correlated with LVEDD and LESD(r=0.456,0.419;0.402,0.437,all P＜0.05).Sestrin2 was positively correlated with TLR7(r=0.641,P＜0.05).ROC curve results showed that the area under the curve(AUC)of serum Sestrin2 combined TLR7 for predicting heart failure in severe pneumonia sepsis patients was 0.940,with sensitivity of 74.9％and specificity of 73.3％.Conclusion The serum levels of Sestrin2 and TLR7 in patients with severe pneumonia and sepsis were elevated and may have good predictive value for patients with heart failure.

Background and purpose:Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis(srICIAM)are poor.Intensified immunosuppressive therapies,including tofacitinib,a novel Janus kinase(JAK)inhibitor,may have some therapeutic benefits.However,due to the lack of sufficient clinical data,the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear.This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM.Methods:This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM.Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group(n=19),while those not treated with tofacitinib were allocated to the control group(n=17).The study compared clinical characteristics,laboratory findings,and imaging results between the two groups.Additionally,follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients.The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University(Approval Number:B2021-275R).This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration.Results:Compared to the control group,and with no significant difference in the cumulative dose and duration of corticosteroids(P＜0.05),the tofacitinib group showed a shorter myocarditis recovery time(median recovery time:86.5 days vs 126.5 days,P=0.021).The myocarditis-related mortality rate was significantly lower in the tofacitinib group than in the control group(5%vs 35%,P=0.025).Conclusion:Tofacitinib may reduce mortality and promote cardiac recovery in srICIAM patients without impeding the anti-tumor effect.It may become one of the potential treatment strategies in the future.

BACKGROUND:Studies have shown that insulin-like growth factor 1/platelet-derived growth factor has an inhibitory effect on fibroblast apoptosis.miR-141-3p in bone marrow stromal cells increases with age and has a relationship with the activation of inflammatory signaling pathways,suggesting that it may be a therapeutic target for lumbar disc herniation. OBJECTIVE:To explore the effects of miR-141-3p on dorsal root ganglion inflammation and lower limb pain in rats with lumbar disc herniation by regulating insulin-like growth factor 1/platelet-derived growth factor. METHODS:Fifty male Sprague-Dawley rats,SPF level,were randomly divided into normal group,model group,miR-NC group,miR-141-3p inhibitor group and miR-141-3p mimics group,with 10 rats in each group.Except for the normal group,animal models of lumbar disc herniation were established in rats by autologous nucleus pulposus transplantation.After successful modeling,rats in the miR-NC,miR-141-3p inhibitor and miR-141-3p mimics groups were injected intrathecally with 10 μL of 20 μmol/L miR-NC,miR-141-3p inhibitor,miR-141-3p mimics,once a day for 28 days,respectively,while those in the normal and model groups were injected with the same volume of saline at the same location at the same time.Paw withdrawal thermal latency threshold was used to evaluate lower limb pain in rats.The mRNA expression of miR-141-3p in dorsal root ganglion tissue was detected by real-time fluorescence quantitative PCR,the levels of inflammatory factors in dorsal root ganglion tissue were detected by ELISA,and the expression of insulin-like growth factor 1/platelet-derived growth factor in dorsal root ganglion tissue was detected by western blot.The correlation between miR-141-3p and insulin-like growth factor 1/platelet-derived growth factor was analyzed. RESULTS AND CONCLUSION:There were no significant differences in all indexes between the miR-NC group and the model group.Paw withdrawal thermal latency threshold was significantly lower in the model group than in the normal group(P＜0.05),significantly lower in the miR-141-3p inhibitor group than the miR-NC group(P＜0.05),and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group(P＜0.05).The mRNA expression of miR-141-3p in dorsal root ganglion tissue was significantly lower in the model group than in the normal group(P＜0.05),significantly lower in the miR-141-3p inhibitor group than in the miR-NC group(P＜0.05),and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group(P＜0.05).The levels of tumor necrosis factor α,interleukin 1β,and interleukin 1 in dorsal root ganglion tissue were significantly higher in the model group than in the normal group(P＜0.05),significantly higher in the miR-141-3p inhibitor group than in the miR-NC group(P＜0.05),and significantly lower in the miR-141-3p mimics group than in the miR-141-3p inhibitor group(P＜0.05).The protein expressions of insulin-like growth factor 1 and platelet-derived growth factor in dorsal root ganglion tissue were significantly lower in the model group than in the normal group(P＜0.05),significantly lower in the miR-141-3p inhibitor group than in the miR-NC group(P＜0.05),and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group(P＜0.05).The expressions of insulin-like growth factor 1 and platelet-derived growth factor showed a positive correlation with miR-141-3p(r=0.904,P＜0.001;r=0.879,P＜0.001).To conclude,miR-141-3p can significantly improve lower limb pain and inhibit inflammation in dorsal root ganglia in rats with lumbar disc herniation,and its mechanism may be related to the promotion of insulin-like growth factor 1/platelet-derived growth factor expression.