Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

Objective:To explore the effect of the combination of robot-assisted total knee arthroplasty and pressure sensor on early postoperative outcomes.Methods:Twenty patients who underwent YUANHUA robot-assisted TKA between September 2024 and December 2024 were prospectively enrolled. After randomization and exclusion of one patient lost to follow-up, 10 patients were included in the pressure-sensor group and 10 in the control (no-pressure) group. In the pressure-sensor group, surgeons used a pressure sensor to assist in soft tissue balancing after osteotomy, whereas in the control group, balancing was performed empirically. In both groups, medial and lateral compartment pressures of the knee at 10°, 45°, 90°, and 120° of flexion were recorded using a pressure sensor prior to component implantation. Clinical outcomes were evaluated preoperatively and at 1 day, 3 days, 1 week, 2 weeks, 6 weeks, and 3 months postoperatively using the visual analog scale (VAS), Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Forgotten Joint Score (FJS).Results:All 20 procedures were completed successfully, and patients were followed for at least 3 months. At 10° of knee flexion, the difference between medial and lateral compartment pressures was significantly smaller in the pressure-sensor group (0.99±59.44 N) than in the control group (97.18±84.34 N; t=-2.948, P=0.009). At 45° of flexion, the corresponding differences were -12.99±36.20 N and 51.48±76.40 N, respectively ( t=-2.411, P=0.032). No significant differences in VAS, KSS, or WOMAC scores were observed between groups preoperatively ( P>0.05). At 3 months postoperatively, the KSS was significantly higher in the pressure-sensor group (174.40±16.39) compared with the control group (138.50±38.35, t=2.722, P=0.014). The WOMAC and VAS scores were significantly lower in the pressure-sensor group (12.70±11.00 and 1.20±0.92, respectively) than in the control group (27.30±18.54 and 2.70±2.00; t=-2.142, P=0.046; t=-2.153, P=0.045). At 2 weeks and 3 months postoperatively, the FJS scores in the pressure-sensor group [70.00±26.06 and 88.07(83.52, 95.83)] were significantly higher than those in the control group [37.92±32.42 and 50.00(32.50, 67.75); t=2.439, P=0.025; Z=-2.466, P=0.014]. Conclusion:The combination of precise osteotomy using robot-assisted TKA and soft tissue balancing guided by a pressure sensor provided more accurate medial-lateral compartment balance and significantly enhanced early postoperative clinical outcomes.

ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 （LPCAT4） in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study， the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis （UALCAN）， Sangerbox and gene expression profile interaction analysis 2 （GEPIA2）. Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors， which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2， UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation， while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells， with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Objective To discuss the efficacy of transcatheter arterial chemoembolization(TACE)in combination with targeted therapy and immune checkpoint inhibitors for advanced hepatocellular carcinoma(HCC),and to identify the influencing factors.Methods A total of 60 patients with advanced HCC,who were admitted to the Air Force Medical Center of China from January 2016 to December 2022,were enrolled in this study.Thirty patients received TACE combined with targeted therapy and immune checkpoint inhibitors(TACE-L-P group),and the other 30 patients received TACE combined with targeted therapy(TACE-L group).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and objective response rate(ORR)were compared between the two groups.Results In the TACE-L group and TACE-L-P group,the median PFS(mPFS)was 7 months and 10 months respectively(P=0.011),the median OS(mOS)was 15.5 months and 29 months respectively(P=0.014).Child-Pugh class B(HR=3.89,95％CI:1.27-11.94,P=0.018)and Barcelona Clinic Liver Cancer(BCLC)stage C(HR=2.83,95％CI:1.32-6.03,P=0.007)were the independent risk factors for OS,while micro wave ablation(HR=0.21,95％CI:0.07-0.63,P=0.005)and TACE-L-P(HR=0.09,95％CI:0.03-0.3,P=0.001)were the independent protection factors for OS.Besides,elevated bilirubin level(HR=1.03,95％CI:1-1.06,P=0.032)and elevated gamma-glutamyl transferase(GGT)level(HR=1.01,95％CI:1-1.01,P=0.002)were the independent risk factors for disease progression,and TACE-L-P(HR=0.27,95％CI:0.09-0.79,P=0.017)was the independent protection factor for disease progression.The ORR and DCR in TACE-L-P group were remarkably higher than those in TACE-L group,which were 43.4％vs 13.3％and 63.4％vs 23.3％respectively,the differences between the two groups were statistically significant(both P＜0.05).Conclusion In treating advanced HCC,TACE combined with targeted therapy and immune checkpoint inhibitors is superior to TACE combined with targeted therapy in therapeutic efficacy.

Objective:To explore the effect of the combination of robot-assisted total knee arthroplasty and pressure sensor on early postoperative outcomes.Methods:Twenty patients who underwent YUANHUA robot-assisted TKA between September 2024 and December 2024 were prospectively enrolled. After randomization and exclusion of one patient lost to follow-up, 10 patients were included in the pressure-sensor group and 10 in the control (no-pressure) group. In the pressure-sensor group, surgeons used a pressure sensor to assist in soft tissue balancing after osteotomy, whereas in the control group, balancing was performed empirically. In both groups, medial and lateral compartment pressures of the knee at 10°, 45°, 90°, and 120° of flexion were recorded using a pressure sensor prior to component implantation. Clinical outcomes were evaluated preoperatively and at 1 day, 3 days, 1 week, 2 weeks, 6 weeks, and 3 months postoperatively using the visual analog scale (VAS), Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Forgotten Joint Score (FJS).Results:All 20 procedures were completed successfully, and patients were followed for at least 3 months. At 10° of knee flexion, the difference between medial and lateral compartment pressures was significantly smaller in the pressure-sensor group (0.99±59.44 N) than in the control group (97.18±84.34 N; t=-2.948, P=0.009). At 45° of flexion, the corresponding differences were -12.99±36.20 N and 51.48±76.40 N, respectively ( t=-2.411, P=0.032). No significant differences in VAS, KSS, or WOMAC scores were observed between groups preoperatively ( P>0.05). At 3 months postoperatively, the KSS was significantly higher in the pressure-sensor group (174.40±16.39) compared with the control group (138.50±38.35, t=2.722, P=0.014). The WOMAC and VAS scores were significantly lower in the pressure-sensor group (12.70±11.00 and 1.20±0.92, respectively) than in the control group (27.30±18.54 and 2.70±2.00; t=-2.142, P=0.046; t=-2.153, P=0.045). At 2 weeks and 3 months postoperatively, the FJS scores in the pressure-sensor group [70.00±26.06 and 88.07(83.52, 95.83)] were significantly higher than those in the control group [37.92±32.42 and 50.00(32.50, 67.75); t=2.439, P=0.025; Z=-2.466, P=0.014]. Conclusion:The combination of precise osteotomy using robot-assisted TKA and soft tissue balancing guided by a pressure sensor provided more accurate medial-lateral compartment balance and significantly enhanced early postoperative clinical outcomes.

Robot and computer navigation assisted joint replacement surgery have the advantages of high operational repeatability, good stability, and high accuracy. In the past decade, its application in clinical practice has become increasingly widespread. However, there may be some special adverse events during robot and computer navigation assisted joint arthroplasty surgery. If there are problems with robots, navigation equipment, or process links, it can cause robot assisted surgery to be forced to abortion and switch to manual surgery. There are reports that the incidence of abortion of robotic surgery due to such reasons is as high as 22%. There may be skin and soft tissue infections around the fixed pin of the tracker, as well as fractures through tracking pin site. Most symptoms of soft tissue infections around the pin track are mild and can be cured through local dressing changes and other treatments. Fractures through tracking pin site have a significant impact on patients, but the incidence is low, mostly reported as individual cases. As of now, a total of 29 cases have been reported in the literature, of which 17 cases (59%) occurred in the femoral shaft, 3 cases (10%) in the femoral epiphyseal end, 7 cases (24%) in the tibial shaft, and 2 cases (7%) in the tibial epiphyseal end. 10 cases (34%) were non displaced or occult fractures, which were cured through conservative treatment. The remaining 19 cases (66%) were displaced fractures, of which 4 cases (14%) were treated with open reduction and internal fixation, 14 cases (48%) were treated with intramedullary nails, and 1 case (3%) underwent total keen revision surgery. Neurovascular damage caused by fixed pin is relatively rare. Research has found that the incidence of such special complications is very low, and most of them are relatively easy to manage. But surgeons should remain vigilant and standardize surgical operations, such as installing fixed pin with care and caution, to avoid the occurrence of such special complications as much as possible.

BACKGROUND:The key to preventing the recurrence of intrauterine adhesions is to reconstruct the endometrium with normal function.The latest breakthrough in the treatment of recurrent intrauterine adhesions in and outside China is the use of degradable materials to prepare hydrogels to prevent the recurrence of adhesions. OBJECTIVE:To review the research advance in hydrogel-promoted endometrial repair in intrauterine adhesions. METHODS:PubMed,Web of Science,China National Knowledge Infrastructure(CNKI),and WanFang databases were searched systematically,with the keywords"intrauterine adhesions,endometrial injury,endometrium regeneration,hydrogel"in Chinese and English.Relevant articles published in each database from January 1990 to March 2023 were collected. RESULTS AND CONCLUSION:In recent years,research on hydrogel-promoted endometrial repair in uterine adhesions in and outside China has made some progress and plays an important role in the prevention and treatment of intrauterine adhesions and the promotion of endometrial repair:(1)As an important carrier in tissue engineering,hydrogel itself has excellent biocompatibility,biodegradability and three-dimensional network structure,which can be better applied in the treatment of intrauterine adhesions.(2)The hydrogel-based carrier system can promote the proliferation and differentiation of endometrial epithelial cells by transporting drugs/biologics/stem cells,and restore normal uterine morphology to prevent adhesion recurrence.(3)Hyaluronic acid hydrogels can not only meet good biocompatibility,but also promote the proliferation and differentiation of endometrial epithelial cells,and will be hydrolyzed by corresponding enzymes in utero,without affecting the normal metabolism of the body.They are currently commonly used uterine anti-adhesion agents in the clinic and are also the most commonly used hydrogel carriers in tissue engineering research.(4)Poloxamer hydrogel with excellent temperature-sensitive properties can rapidly gelate into the body,quickly form a physical barrier,and can play a slow-release effect on carrying substances and provide a platform for cell growth/adhesion.(5)There are broad prospects for the preparation of therapeutic hydrogels using materials with different characteristics,such as temperature-sensitive hydrogels,pH-responsive hydrogels and photosensitive hydrogels,but there are still many problems to be solved,such as the safety of the hydrogel system,whether the degradation products cause immune reactions,and whether they have an impact on the normal body's menstrual period.A large number of animal experiments and clinical trials are needed to verify its safety and efficacy,and continuously improve the treatment strategy.

Objective:To systematically evaluate the actual experience and needs of family caregivers for cardiac arrest patients.Methods:Qualitative research on the real experience and needs of family caregivers in patients with cardiac arrest was electronically searched in databases such as PubMed, CINAHL, and Embase. Two researchers independently screened the literature, evaluated its quality, and integrated the research results. The search period was from database establishment to May 1, 2023.Results:A total of 15 articles were included, and 51 research results were extracted. The similar results were summarized into nine categories and integrated into three results, including sudden changes in life and substantial impacts; challenges in controlling complex emotions, and multiple psychological experiences; multidimensional needs.Conclusions:Family caregivers' actual experiences and requirements for cardiac arrest patients are diverse. Medical and nursing staff need to pay attention to the emotional experiences of family caregivers and meet their multidimensional needs.