ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

Objective:To investigate the effect of ligation methods of inferior mesenteric artery (IMA) on preserving left colic artery (LCA) in laparoscopic radical resection of rectal cancer.Methods:The prospective randomized controlled study was conducted. The clinical data of 864 patients who underwent laparoscopic radical resection of rectal cancer at Renji Hospital of Shanghai Jiaotong University School of Medicine from January 2020 to December 2024 were selected. Patients were randomly divided into the low ligation group and high ligation group using a random number table. Patients of the low ligation group underwent laparoscopic radical resection of rectal cancer with preserving LCA by low ligation of IMA and apical lymph node dissection, and patients of the high ligation group underwent laparoscopic radical resection of rectal cancer with traditional high ligation of IMA. Observation indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postoperative pathological examination; (4) postoperative recovery. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parametric test. Results:(1) Grouping of the enrolled patients. A total of 864 patients with rectal cancer who underwent laparoscopic radical resection of rectal cancer were screened for eligibility, including 410 males and 454 females, aged (63±11)years. All 864 patients were randomly divided into the low ligation group and high ligation group, with 432 patients in each group. There was no significant difference in gender, age, body mass index, carcinoembryonic antigen, distance from tumor to anal margin, diabetes, hypertension, neoadjuvant radiochemotherapy, IMA subtypes and IMA length between the two groups ( P>0.05), ensuring comparability. (2) Intraoperative conditions. All patients of the two groups successfully completed surgery, with no errors in blood vessel ligation during operation or conversion to open surgery. There was a significant difference in time of IMA dissection between the low ligation group and high ligation group [(31±11)minutes vs. (28±9)minutes, t=4.39, P<0.05], and there was no significant difference in total operation time, volume of intra-operative blood loss or prophylactic stoma rate between the two groups ( P>0.05). (3) Postopera-tive pathological examination. There was a significant difference in the number of lymph node dissected between the low ligation group and high ligation group (1.8±1.4 vs. 1.5±1.4, t=2.51, P<0.05), and there was no significant difference in tumor diameter, the total number of lymph node dissected, total lymph node positive status, No.253 lymph node positive status, TNM staging between the two groups ( P>0.05). (4) Postoperative recovery. The time to postoperative first flatus and the number of anastomotic leakage of patients in the low ligation group were (74±22)hours and 16 cases, versus (78±20)hours and 31 cases in the high ligation group, respectively, showing significant differences in the above indicators between the two groups ( t=2.52, χ2=5.06, P<0.05). There was no significant difference in the time to postoperative initial liquid food intake, duration of post-operative hospital stay, duration of abdominal drainage tube indwelling, duration of anal tube indwelling, postoperative wound infection, pulmonary infection, intestinal obstruction, or urinary dysfunction between the two groups ( P>0.05). None of patients in the two groups had readmission or death during the postoperative 30 days. Conclusion:Low ligation of IMA in laparoscopic radical resection of rectal cancer can guide precise LCA preservation, which is beneficial for accelerating the recovery of intestinal function and reducing the incidence of anastomotic leakage.

BACKGROUND:Iron overload is an independent factor inducing osteoporosis,but the action mechanism is currently unclear.Therefore,exploring the effects of iron overload on osteoblast-related cells will help to deeply understand the pathogenesis of osteoporosis and provide potential strategies for osteoporosis treatment.OBJECTIVE:To explore the effects of iron overload environment on osteoblast precursor cell activity,ferroptosis,and osteogenic differentiation.METHODS:Osteoblast precursor cells(MC3T3-E1 cells)were divided into blank group,iron overload group,fer-1 group,and deferoxamine group.The iron overload group was treated with 300 μmol/L ammonium ferric citrate in the culture medium for 48 hours to simulate the iron overload microenvironment.The cells in fer-1 group and deferoxamine group were pretreated with 5 μmol/L antioxidant fer-1 and 5 μmol/L deferoxamine for 8 hours,respectively,and then added with 300 μmol/L ammonium ferric citrate for 48 hours.CCK-8 assay was used to determine the cell viability.Intracellular reactive oxygen species levels were detected employing a reactive oxygen species fluorescent probe.Changes in mitochondrial membrane potential were monitored with a mitochondrial membrane potential fluorescent probe.Mitochondrial morphology was observed employing transmission electron microscopy.Cellular glutathione levels were measured with a reduced glutathione colorimetric assay kit.Lipid peroxidation levels were assessed with a malondialdehyde colorimetric assay kit.Cellular ferrous ion levels were determined with a ferrous ion colorimetric assay kit.The osteogenic and mineralization capabilities of the cells were verified by alkaline phosphatase staining and alizarin red staining.Collagen secretion ability was detected using Sirius Red staining.The expression of osteogenic/ferroptosis-related genes and proteins was examined through reverse transcription quantitative polymerase chain reaction and western blot analysis.RESULTS AND CONCLUSION:(1)In an iron-overload environment,the mitochondrial membrane potential of cells decreased and their structure was compromised,with an elevation in intracellular lipid peroxidation levels and a downregulation of genes and proteins associated with ferroptosis resistance.However,pretreatment with fer-1 and deferoxamine led to an increase in mitochondrial membrane potential and partial restoration of morphology,a reduction in intracellular lipid peroxidation levels,and an upregulation of genes and proteins related to ferroptosis resistance.(2)In an iron-overload environment,the levels of cellular alkaline phosphatase,the formation of mineralized nodules,and the synthesis of collagen fibers were all found to be decreased.Pretreatment with fer-1 and deferoxamine was observed to upregulate the expression of osteogenic differentiation in cells.(3)In summary,iron overload could increase intracellular oxidative stress levels,mediate ferroptosis in MC3T3-E1 cells and inhibit osteogenic differentiation,thereby inducing osteoporosis.Therefore,maintaining iron homeostasis and inhibiting osteogenesis-related ferroptosis may be potential strategies to prevent or treat osteoporosis.

OBJECTIVE To analyze the clinical characteristics and pathogens for mixed infections in children with pertussis,so as to references for clinical diagnosis and treatment.METHODS A retrospective analysis was conduc-ted on the clinical data of 350 children diagnosed with pertussis and hospitalized in Wuhan Children's Hospital from Jan.2022 to Dec.2023.The clinical characteristics,peak white blood cell count,peak lymphocyte ratio,high-sensitivity C-reactive protein or C-reactive protein,procalcitonin and complications were compared between different age groups,as well as between the single infection group and the mixed infection group.RESULTS Mixed infections were observed in 291 children(83.14％),predominantly viral(63.43％,222/350),with human rhinovirus/enterovirus being the most common(32.57％,114/350).For children aged＜6 months,6 months to＜1 year and 1 to＜3 years,the incidence of family contact history of cough,panting,hasty breathing,respira-tory failure,peak white blood cell count and peak lymphocyte ratio were all higher than those aged 3 to＜6 years and≥6years(all P＜0.05).The incidence of post-cough vomiting was higher in children aged 6 months to＜1 year and 1 to＜3 years compared to other age groups(P＜0.05).The length of hospital stay decreased with in-creasing age(P＜0.05).The proportions of children with paroxysmal spasmodic cough,post-cough cyanosis,post-cough flushing,coughing spells,inspiratory three concave sign,pneumonia and pulmonary phlegm rales all generally decreased with age(all P＜0.05).Nodding respiration was only observed in children aged＜1 year(P＜0.05).The incidence of fever,co-infection with bacteria and Mycoplasma pneumoniae infection was higher in children aged 6 months to＜1 year,1 to＜3 years,3 to＜6 years and ≥ 6 years compared to those aged＜6 months(all P＜0.05).The incidence of fever was higher in the mixed infection group than that in the single in-fection group(P＜0.05).Children in the single infection group had longer hospital stays,higher incidence of par-oxysmal spasmodic cough,nocturnal cough,post-cough flushing,coughing spells,pulmonary phlegm rales and higher peak lymphocyte ratio(all P＜0.05).The incidence of paroxysmal spasmodic cough was higher in the sin-gle infection group for children aged＜3 months(P＜0.05).CONCLUSIONS The younger children with pertussis have a higher proportion of family contact history of cough and are more prone to clinical manifestations such as paroxysmal spasmodic cough,post-cough vomiting,post-cough cyanosis,and pneumonia.They also have higher peak white blood cell counts,peak lymphocyte ratios and longer hospital stays.As children'age increased,the in-cidence of fever,bacterial,and mycoplasma infections also increased.The types of pathogens in mixed infections varies with patients' age and pertussis mixed infections may mask typical clinical symptoms.

The Animal Molecular Biology course is a crucial and foundational course for both Animal Medicine and Animal Science majors.Apart from teaching fundamental principles of molecular biology,the course provides updated applications of these principles in the field of animal science research.Im-portantly,it plays a fundamental role in cultivating students'research capabilities.With the rise of over-whelming information and their optimal utilization,the demand for integrating digital education with tradi-tional teaching methods is increasing.Based on the five years of teaching practice,this paper summarizes four highlights of the course:the construction of teaching resource,the restructuring of teaching syllabus,the adjustment of classroom teaching hours,and the improvement of assessment methodology.It focuses on Electronic-Learning"E(E-Learning)",offline classroom intensive teaching"C(Classroom)",and post-class extension to construct a blended teaching model that integrates Electronic-Learning and Class-room teaching,namely the"E+C"blended teaching model.Offline classroom teaching emphasizes the combination of theory and knowledge systems,while online Electronic-Learning mainly focuses on popular science and interesting aspects to stimulate students' interests and enthusiasm in learning.Over five years of practice,the"E+C"blended model has been proven to exert a good teaching effect.Students have reported significant gains from the course,with tightly connected and strongly complementary class-room teaching and E-Learning,which greatly aids in mastering professional knowledge.It also cultivates intrinsic motivation for learning and enhances the sense of accomplishment in acquiring knowledge,sig-nificantly improving teaching effectiveness.

Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.

Objective:To explore the equity and driving path of primary healthcare human resource allocation across 31 provinces in China,providing references for optimizing such allocations.Methods:Using data from the 2022 primary healthcare human resources in 31 provinces in China,the Health Resource Density Index(HRDI)was used to measure the equity of primary healthcare human resource allocation.The fuzzy-set Qualitative Comparative Analysis(fsQCA)was applied to construct configurational pathways influencing on allocation patterns.Results:In 2022,the HRDI for primary healthcare human resources in China was 2.349 0 in the East,1.198 6 in the Central region,and 0.775 2 in the West.Configurational analysis revealed three paths that promote high equity:the internal-external balance-driven model(H1),the government-led model(H2),and the economic-demand combined model(H3),with overall consistency and coverage of 0.955 and 0.794,respectively.Seven paths lead to low equity:internal-external constraint models(L1,L2),economic constraint models(L3),and demand constraint models(L4,L5,L6,L7),with overall consistency and coverage of 0.967 and 0.795,respectively.Conclusions:Significant regional disparities exist in the equity of primary healthcare human resource allocation in China.Population density is a critical factor influencing allocation equity.The collaboration of various factors contributes to enhancing the equity of primary healthcare human resources distribution.Therefore,future efforts to enhance equity should focus on promoting inter-regional mobility and resource sharing,while precisely addressing regional shortcomings to achieve high equity in primary healthcare human resource allocation.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To evaluate the clinical value and safety of an intraperitoneal chemotherapy port technique in patients with gastric cancer and peritoneal metastases undergoing intraperitoneal chemotherapy.Methods:This was a retrospective, descriptive case analysis. From November 2022 to October 2024, patients diagnosed with gastric cancer and peritoneal metastases at Wuxi Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine with an expected survival >3 months, underwent laparoscopic exploration combined with implantation of an intraperitoneal chemotherapy port [PORT-A-CATH II system (Model 21-4055-24)] implantation. The procedure was as follows: (1) after laparoscopic exploration, a 4-cm skin incision was made at a predetermined site and a subcutaneous pocket created by dissecting to the muscle fascia and removing subcutaneous fat as needed to position the port septum 0.5-1.0 cm from the skin surface; (2) under direct laparoscopic visualization, the abdominal cavity was punctured and a guidewire inserted, followed by an 8.5 Fr sheath, through which a catheter with three trimmed side holes was placed after removal of the sheath; (3) the catheter length in the abdominal cavity was adjusted to 25–30 cm and the catheter trimmed, and connected to the port base, ensuring it extended beyond the connector's visible hole; (4) the whole port was placed within the subcutaneous pocket, and non-absorbable sutures used to create a double purse-string suture at the catheter's abdominal entry, forming an anti-reflux ring; (5) non-absorbable sutures were used to securely fix the port to the fascia through its four base holes and the exposed catheter segments on the fascia sutured and buried; (6) patency was confirmed by injecting saline and followed by intermittent skin closure provided there was no bleeding; and (7) the catheter tip was positioned in the pelvic cavity under laparoscopic guidance. Postoperatively, the patients underwent normothermic intraperitoneal and systemic treatment. The port infusion protocol involved disinfecting the skin (>10 cm diameter) around the port, confirming the puncture site, inserting a Huber needle vertically at 90° to the port base, infusing 100 mL saline to ensure patency, followed by continuous infusion of 1000 mL paclitaxel solution, and sealing with 20 mL saline before removing the needle. No saline flushing was required between chemotherapy infusions. The primary outcomes were the incidence and management of complications post-port implantation.Results:The study cohort comprised 225 patients with gastric cancer and peritoneal metastases. Using standardized port implantation and postoperative puncture procedures, the complication rate during follow-up was 14.2% (32/225), including effusion in 14 patients (6.2%), port infection in 10 (4.4%), incision dehiscence in four (1.8%), port inversion in two (0.9%), hematoma in one (0.4%), and catheter rupture in one (0.4%). Seventy-five percent (24/32) of patients with complications recovered and continued using the port after conservative treatments (e. g., aspiration of effusions, antibiotic therapy, incision management), whereas the remaining 25.0% (8/32) with complications required surgical removal of the port because the treatment was ineffective. The presence of preoperative ascites ( P=0.019) and peritoneal cancer index score>15 ( P=0.038) were significantly associated with development of complications. Conclusions:Our standardized procedure for intraperitoneal chemotherapy port implantation is safe and feasible for patients with gastric cancer and peritoneal metastases, having a low overall complication rate. Most complications can be successfully managed with conservative treatment, the device thus providing reliable support for intraperitoneal chemotherapy.

Objective To evaluate the dosimetric impact of interfractional bladder fullness variation in volumetric modulated arc therapy for cervical cancer using artificial intelligence-assisted cone-beam CT(CBCT)image segmentation,and propose an imaging-based quantitative assessment criterion for bladder fullness,providing an objective basis for assessing bladder filling status during clinical treatment.Methods Fifty patients receiving volumetric modulated arc therapy for cervical cancer were selected.The criterion for determining bladder fullness was as follow:if the bladder longitudinal diameter measured on the CBCT mid-sagittal plane was greater than half of the bladder longitudinal diameter measured on the localizable CT,it was defined as≥50%bladder fullness;otherwise,it was defined as<50%bladder fullness.Based on this criterion,two CBCT images were selected for each patient(representing fractions with≥50%and<50%fullness,respectively).Borui auto-contouring system was applied to re-contour the target areas and organs at risk,followed by dose recalculation.Results Compared with≥50%bladder fullness group,<50%bladder fullness group had significantly increased bladder V40,and small bowel Dmax,Dmean,V55,V45,V40(P<0.05),indicating that during interfractional radiotherapy,a CBCT-measured bladder longitudinal diameter less than half of the bladder longitudinal diameter measured on the localizable CT could serve as a predictor for significantly increased radiation dose to the bladder and small bowel.Correlation analysis revealed that bladder volume change showed a positive correlation with bladder Dmax change(R=0.45),a significant negative correlation with bladder V30(R=-0.37),and negative correlations with small bowel Dmax,Dmean,V55,V45,V40(R=-0.31,-0.41,-0.39,-0.49,-0.61).The correlation results indicate that increasing bladder fullness could reduce the radiation dose to the bladder and small bowel.Conclusion Artificial intelligence-assisted segmentation confirms that in interfractional radiotherapy for cervical cancer,when the CBCT-measured bladder longitudinal diameter is less than half of the longitudinal diameter measured on the localizable CT,there is a significant increase in radiation dose to OAR.Maintaining an ideal state of bladder fullness contributes to reducing the radiation dose to the bladder and small bowel.It is crucial to provide patients with adequate bladder management education before treatment and implement strict bladder volume management strategies during treatment fractions.