The 3D-printed radiotherapy X-ray dose compensators can significantly improve the spatial accuracy of radiation dose distribution and the homogeneity of the target volume in superficial tumor radiotherapy while reducing the dose to normal tissues by conforming to individual patient surface contours. Their clinical application value is becoming increasingly prominent. However, standardized evaluation systems or technical specifications for such products are currently lacking both domestically and internationally, leading to inconsistent performance assessment and hindering the verification of their clinical safety and effectiveness. To ensure radiotherapy quality and patient health and safety, this study proposed a set of technical specifications for evaluating radiotherapy X-ray dose compensators by reviewing their physical, functional, and safety performance, as well as software and clinical-engineering interaction performance. Furthermore, based on existing technical standards and regulatory review guidelines, quantitative evaluation methods were explored, including computed tomography number calibration phantom testing and dose compensation performance verification. This work aims to provide a scientific reference for future product development, standard formulation, and regulatory review.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the most common chronic liver disease worldwide. Its pathological process is centered on the “two-hit” theory， with gut-liver axis dysregulation running through the entire disease course from steatosis to liver cirrhosis and even hepatocellular carcinoma， and it forms an extensive cross-system regulatory mechanism with the metabolic， cardiovascular， renal， and psychological and nervous systems through multi-dimensional pathways such as the “gut-liver-brain axis”， the “liver-kidney axis”， and the “liver-heart axis”. Disease progression is not limited to the liver itself， and it also involves functional imbalance of multiple organ systems throughout the body. This article systematically elaborates on the association mechanism of “liver pathological progression-multi-axis regulation-comorbidity occurrence” in MAFLD， proposes synergistic management strategies integrating early screening based on risk stratification， targeted intervention， and multidisciplinary diagnosis and treatment， and analyzes the limitations of current research and future development directions， in order to provide a theoretical basis and practical guidance for precise diagnosis and treatment and individualized management of MAFLD.

ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

The connotation of the "four-dimensional pivot-earth" qi transformation mode is a dialectical system of the ascending and descending of yin-yang qi movement， which presented as "the middle Jiao showing earth qi mediating， the left wheel showing water and wood ascending， and the right wheel showing fire and metal converting and descending". Based on this dialectical thinking， it is believed that the core pathogenesis of myasthenia gravis is deficiency of center qi and transportation failure to pivot-earth； the middle-stage characteristics of the disease progression are the loss of mediation of the central qi， resulting in water coldness and wood constraint， and clear yang failing to ascend； the final outcome of this disease is the loss of astringeing of lung metal and qi sinking. The treatment should be based on the rule of qi movement， so for the start-stage， Buzhong Yiqi Decoction （补中益气汤） should be used as the basis to nourish the earth and consolidate the root， and restrengthen the middle qi； for the middle-stage， herbs like Yingyanghuo （Epimedium brevicornu Maxim.）， Bajitian （Morinda officinalis How） could be combined to warm the water and soothe the wood， raise yang and boost qi； for the final stage， plus Sini Decoction （四逆汤） to astringe metal to stop collapse， and powerfully supplement original qi. All these medicinals can promote pivot-earth re-transportation， four-dimensional transformation， and regular circulation of qi movement， so as to provide thoughts for improving the clinical effectiveness of myasthenia gravis.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for diagnosing malignant adnexal tumors.Methods Totally 112 patients with single adnexal masse were retrospectively enrolled and divided into benign adnexal tumor group(benign group,n=73)and malignant adnexal tumor group(malignant group,n=39).Clinical data,laboratory indicators,ovarian-adnexal ultrasound reporting and data system(O-RADS)classification based on conventional ultrasound(US),CEUS manifestations and CEUS classification of benign and malignant tumors were compared between groups.Multivariable logistic regression analysis of clinical and laboratory indicators being statistically different between groups,as well as US O-RADS classification and CEUS classification was performed to screen the independent predictors of malignant adnexal tumors,and combined models were constructed using forward stepwise regression method.The efficacy of each independent predictor and combined model for diagnosing malignant adnexal tumors was analyzed.Results Statistical differences of carbohydrate antigen 125(CA125),US O-RADS classification,enhancement time and level of CEUS,as well as CEUS classification were found between groups(all P＜0.05).CA125,US O-RADS classification and CEUS classification were all independent predictors of malignant adnexal tumors(all P＜0.05).Combined model Ⅰ,Ⅱ and Ⅲ were constructed based on CA125+CEUS classification,US O-RADS classification+CEUS classification and CA125+US O-RADS classification+CEUS classification,respectively.The area under the curve(AUC)of single CA125 level,US O-RADS classification,CEUS classification and combined model Ⅰ,Ⅱ and Ⅲ for diagnosing malignant adnexal tumor was 0.708,0.809,0.908,0.918,0.945 and 0.954,respectively.AUC of combined model Ⅲ was higher than that of combined model Ⅰ(Z=-2.142,P=0.032),while no significant difference of AUC was found between combined model Ⅱ and Ⅰ nor Ⅱ and Ⅲ(both P＞0.05).Conclusion CEUS could be used to effectively diagnose malignant adnexal tumor.Combining with CA125 level and US O-RADS classification could significantly improve its diagnostic efficacy.

Objective:To retrieve, evaluate and integrate the evidence related to postoperative exercise rehabilitation for hip fracture in elderly frail patients, and provide reference for clinical rehabilitation nursing.Methods:Evidence on postoperative exercise rehabilitation of hip fractures in elderly frail patients was systemically retrieved in the guideline websites, professional association websites and databases, such as BMJ Best Practice, UpToDate, PubMed, Web of Science, CINAHL, Cochrane Library, Embase, Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang and VIP, including Best practices, guidelines, clinical decisions, evidence summaries, systematic reviews, and expert consensus. The retrieval time was from the establishment of the database to March 31, 2024.Results:A total of 33 articles were involved, including 12 guidelines, 2 clinical decisions, 7 systematic reviews, 7 expert consensuses, 5 evidence summaries. Forty pieces of evidence were summarized in 7 aspects: the role of exercise, exercise assessment, exercise planning, exercise content, exercise intensity, exercise adherence, exercise nursing, exercise guidance.Conclusions:Healthcare professionals should combine patients' tolerance, rehabilitation goals, and specific clinical situations to target and guide patients in exercise rehabilitation to promote the recovery of postoperative limb function, mitigate frailty, and improve the quality of life.

Objective:To explore the efficacy and its related factors of rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS).Methods:It was a single-center retrospective study. The clinical data of FRNS/SDNS children first treated with RTX in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2016 to September 1, 2023 were collected. The number of relapse within 1 year before and after RTX treatment, the time to first relapse after RTX treatment, and the time to B-cell reconstitution were analyzed. At the first treatment, a single dose of RTX was given at 375 mg/m 2, with a maximum dose of 500 mg, once a week, for 1 to 4 doses. The count of CD19 + lymphocytes in the peripheral blood of the children was continuously monitored. If B-cell reconstruction was performed, the decision on whether to proceed to the next course of RTX treatment was made based on clinical manifestations. Kaplan-Meier method was used to analyze relapse-free survival rate after receiving RTX. Cox proportional hazards regression model was used to analyze the related factors of relapse after RTX treatment. Results:A total of 98 FRNS/SDNS children receiving RTX treatment were enrolled, including 75 males (76.5%). The age at onset was 4.0 (1.9, 7.1) years and age of receiving RTX was 11.3 (8.5, 13.5) years. There were 90 children (91.8%) achieving complete remission, while 8 patients (8.2%) did not respond to RTX treatment, and 3 patients (3.1%) progressed to end-stage kidney disease after receiving RTX. The relapse-free survival rates at 6 months and 1 year after RTX treatment were 83.3% (75/90) and 57.9% (22/38), respectively. The frequency of relapse 1 year after RTX treatment decreased compared to 1 year before RTX treatment ( Z=-7.398, P<0.001). Compared with children without relapse during the period of B-cell depletion, relapsed children had a higher number of relapse within one year after RTX treatment ( Z=5.246, P<0.001). The time to first relapse after RTX treatment was 8.3 (4.6, 13.9) months in 51 relapse patients. Compared with children receiving 1 dose of RTX in the first course, those receiving 2 or more doses had a longer time to the first relapse ( Z=2.983, P=0.003). There was no statistically significant difference in time to the first relapse between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). The reconstruction time of B cells after the first course of RTX was 6.9 (5.3, 9.0) months. Compared to children receiving one dose of RTX in the first course, those receiving two or more doses had a longer B-cell reconstitution time ( Z=2.739, P=0.006). There was no statistically significant difference in B-cell reconstitution time between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). Univariate Cox regression analysis showed that recurrence after calcineurin inhibitor (CNI) treatment before RTX treatment and the number of recurrence in one year before RTX treatment were correlated factors of recurrence after RTX treatment (both P<0.05). Multivariate Cox regression analysis showed that recurrence after CNI treatment before RTX treatment was an independent correlated factor of relapse after RTX therapy ( HR=3.496, 95% CI 1.245-9.818, P=0.018). Infusion reactions occurred in 10 patients (10.2%) and infections were observed in 24 patients (24.5%) during B cell depletion. No serious adverse events occurred. Conclusions:RTX is well tolerated and effective in treating FRNS/SDNS. Recurrence after CNI treatment before RTX treatment may be an independent related factor of relapse after RTX treatment.

Objective:To evaluate the effectiveness and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with stage 4/M neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter clinical trial conducted by Sun Yat-sen Memorial Hospital, Children′s Hospital of Nanjing Medical University, Children′s Hospital, Zhejiang University School of Medicine, the First Affiliated Hospital of Guangxi Medical University, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. From March, 2019 to August, 2023, 25 children with confirmed with stage 4/M NB and received allo-HSCT were enrolled. The patients received either unrelated cord blood transplantation (UCBT) or peripheral blood stem cell transplantation (PBSCT). Conditioning regimens for UCBT was fludarabine+busulfan+cyclophosphamide+topotecan, and for PBSCT was fludarabine+busulfan+melphalan+thiotepa+antithymocyte globulin, respectively. Until the last follow-up date of September, 2023, the overall survival (OS) rate and event free survival (EFS) rate were analyzed to evaluate efficacy. The engraftment rate and transplant-related complications were statistically assessed to evaluate safety. Survival analysis was performed using the Kaplan-Meier method.Results:Of the 25 patients, there were 15 males and 10 females. The age at transplantation was 5.7 (3.8, 7.3) years. The engraft rate was 100%, with recovery time of neutrophil as 15.7 (12.5, 17.0) d, and the recovery time of platelets as 33.5 (18.0, 48.0) d. Seventeen of the 25 children (68%) developed acute graft versus host disease (aGVHD), occurred at 18.0 (13.0, 22.5) d after transplantation, including 13 of grade Ⅲ-Ⅳ cases. The main sites of aGVHD were skin and intestinal tract. After treatment, 13 cases improved, 4 patients developed chronic graft-versus-host disease (cGVHD). After allo-HSCT, 14 children received maintenance therapy. Twenty of the 25 patients survived, the 2-year cumulative OS rate was (80±9)%, and 2-year EFS rate was (56±11)%. Nine cases (36%) relapsed, the time from allo-HSCT to disease relapse was 10.9 (5.5, 16.0) months. Five cases (20%) died. The hematopoietic stem cell transplantation associated mortality rate was 4% (1/25).The 2-year OS rate of patients who had partial remission prior to allo-HSCT was significant lower than those who had complete remission prior to allo-HSCT ((33±25)% vs. 100%, P=0.037). Conclusion:allo-HSCT is an effective treatment for patients with stage 4/M NB.