BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective To explore the active monitoring strategies for hypoglycemia in hospitalized dia-betic patients,as well as their clinical symptom characteristics and influencing factors.Methods A retrospec-tive search was conducted on all inpatients in a tertiary hospital in 2023.The hospital's electronic medical re-cord system was manually retrieved through the inpatient numbers of the patients.Adult inpatients with dia-betes who experienced hypoglycemia were included as the research subjects,and the general conditions and possible hypoglycemia-related risk factors were collected.Embed the hypoglycemic electronic trigger program in China Hospital Pharmacovigilance System(CHPS),reviewed the original medical records of patients with positive trigger triggering,and calculated the positive predictive value(PPV).Searched for the number of hy-poglycemic adverse reaction cases voluntarily reported by this hospital during the same period from National Adverse Reaction Monitoring System and compared with the actual number of hypoglycemic cases discovered.Patients with suspected drug-induced hypoglycemia were divided into the symptomatic group and the asymp-tomatic group based on whether they presented hypoglycemia-related symptoms.Multivariate logistic regres-sion analysis was applied to analyze the influencing factors.Results A total of 1 001 adult hospitalized diabet-ic patients with hypoglycemia were included in the study.Among them,725 cases were suspected of drug-in-duced hypoglycemia,and 495 cases were suspected of hypoglycemia caused by drug interactions.After manual review,131 cases of drug-induced hypoglycemia patients had clinical symptoms,and hypoglycemic adverse re-action events should be reported,PPV of this trigger for symptomatic hypoglycemia was 18.1%(131/725).However,the number of hypoglycemic adverse reactions spontaneously reported through National Adverse Reaction Monitoring System by this hospital during the same period was 4 cases,and the reporting rate was only 3.1%(4/131).Multivariate logistic regression analysis showed that aging and grade 2 hypoglycemia were risk factors for the occurrence of related symptoms in patients with suspected drug-induced hypoglycemia(P<0.05),while surgery,type 2 glucosuria,unclassified diabetes,and the use of insulin secretagogues were protective factors(P<0.05).Conclusion Drug-induced hypoglycemia dominates among hospitalized diabetic patients,and age,hypoglycemia grade,inpatient department using insulin secretagogues,diabetes diagnosis and classification are closely related to the occurrence of clinical hypoglycemia-related symptoms.Active monito-ring through CHPS can effectively increase the detection rate and reporting rate of hypoglycemic adverse e-vents in hospitalized diabetic patients.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Gallstones are the primary benign disease diagnosed and treated in biliary surgery.With the development of medical technology and the increasing awareness of health among the population,the detection rate of gallstones has been increasing annually,with the majority being asymptomatic or mild cases.Currently,the clinical treatment of gallstones mainly includes observation,conservative,or surgical treatment(laparoscopic cholecystectomy).However,there remains some controversy regarding the clinical management of these patients.For asymptomatic or mild gallstones,the main point of contention in both academic and clinical settings is how to determine the indications for cholecystectomy.This article reviews relevant literature from both domestic and international sources,addressing the controversies surrounding the clinical management of gallstones and the determination of indications for cholecystectomy,and elaborates on these issues from multiple perspectives.

OBJECTIVE: To investigate the effectiveness of spring ligament repair combined with subtalar arthroereisis (STA) and the Kidner procedure for treating children's flexible flatfoot with painful accessory navicular. METHODS: A retrospective analysis was conducted on clinical data from 45 children (45 feet) aged 7-14 years with flexible flatfoot and painful accessory navicular who met the selection criteria and were treated between February 2018 and May 2022. Among them, 23 cases (23 feet) were treated with spring ligament repair combined with STA and Kidner procedure (observation group), while 22 cases (22 feet) received STA with Kidner procedure alone (control group). Comparison of baseline data between the two groups including gender, age, affected side, preoperative visual analogue scale (VAS) score, American Orthopaedic Foot & Ankle Society (AOFAS) score, talonavicular coverage angle (TCA), talus-first metatarsal angle (T1MT), talus-second metatarsal angle (T2MT), talus first plantar angle (Meary angle), calcaneal inclination angle (Pitch angle) showed no significant differences ( P>0.05). The following parameters were recorded and compared between the two groups: operation time, intraoperative blood loss, incision length, hospital stay, time to full weight-bearing, and complication rates. Foot pain and functional recovery were assessed using the VAS score and AOFAS score preoperatively and at last follow-up. Radiographic measurements including TCA, T1MT, T2MT, Meary angle, and Pitch angle were analyzed by comparing preoperative to last follow-up values. RESULTS: Both groups of patients successfully completed the surgery without any procedure-related complications such as vascular, neural, or tendon injury. The operation time in the observation group was significantly longer than that in the control group ( P<0.05). There was no significant difference between the two groups in terms of intraoperative blood loss, incision length, hospital stay, or time to full weight-bearing ( P>0.05). All patients were followed up 23-47 months (mean, 33.7 months). In the control group, 1 patient experienced discomfort during walking, attributed to screw irritation in the sinus tarsi, which resolved after 2-3 months of rehabilitation. None of the remaining patients developed complications such as sinus tarsi screw loosening, peroneal tendon contracture, or wound infection. At last follow-up, the observation group showed significantly better improvements in radiographic parameters (TCA, T1MT, T2MT, Meary angle, Pitch angle) and greater reductions in VAS and AOFAS scores compared to the control group ( P<0.05). CONCLUSION The combined procedure of spring ligament repair, STA, and Kidner procedure for children's flexible flatfoot with painful accessory navicular demonstrates significant improvements in foot appearance, arch collapse correction, and pain relief. This technique offers technical simplicity, minimal intraoperative complications, and satisfactory clinical outcomes.
Humans ; Flatfoot/surgery* ; Child ; Retrospective Studies ; Adolescent ; Male ; Female ; Treatment Outcome ; Tarsal Bones/abnormalities* ; Subtalar Joint/surgery* ; Ligaments, Articular/surgery* ; Orthopedic Procedures/methods* ; Foot Diseases

Objective To explore the value of the albumin-to-alkaline phosphatase ratio(AAPR)with modified Glasgow prognostic score(mGPS)in assessing the response to and prognosis of intravesical Bacillus Calmette-Guérin(BCG)therapy in patients with non-muscle invasive bladder cancer(NMIBC).Methods A total of 153 high-risk NMIBC patients treated with intravesical BCG in our hospital during Jan.2018 and Oct.2021 were enrolled.Patients were divided into response and non-response groups based on the treatment efficacy,and into good and poor prognosis groups based on the clinical outcomes.AAPR and mGPS were calculated.The relationship between AAPR,mGPS and BCG treatment non-response was analyzed with multivariate logistic regression.Clinical data and scores were compared between prognosis groups.The associations between AAPR,mGPS,and poor prognosis after BCG treatment were assessed with a Cox proportional hazards model.Patients were stratified into high-and low-A APR groups,and into mGPS 0,1,and 2 groups.Kaplan-Meier survival curves were plotted for progression-free survival(PFS)across different AAPR and mGPS strata.The diagnostic performance of AAPR combined with mGPS in predicting treatment non-response and poor prognosis was evaluated using receiver operating characteristic(ROC)curves.Results Among the 153 patients,the response rate to BCG treatment was 71.90％(110/153),the 3-year poor prognosis rate was 45.75％(70/153),and the 3-year PFS rate was 54.25％(83/153).Increased AAPR was identified as an independent protective factor for both treatment response and good prognosis,while higher mGPS was an independent risk factor(P＜0.05).The 3-year PFS rate was significantly higher in the high-AAPR group than in the low-A APR group(P＜0.001).Among the mGPS groups,the 3-year PFS rate was lowest in the mGPS 2 group,followed by mGPS 1 and mGPS 0 groups(P＜0.001).The area under the ROC curve(AUC)for AAPR with mGPS in predicting BCG treatment non-response and poor prognosis was 0.864 and 0.901,respectively,significantly higher than using AAPR(0.774,0.781)or mGPS alone(0.798,0.809)(P＜0.05).Conclusion Lower AAPR and higher mGPS are associated with non-response and poor prognosis in NMIBC patients undergoing intravesical BCG therapy.The combination of AAPR and mGPS has high predictive value.

Kidney transplantation is widely recognized as the optimal treatment for children with end-stage renal disease(ESRD),offering significant improvements in growth,development,and long-term quality of life compared with prolonged dialysis.However,kidney transplantation in low-age(＜5 years old)and low-weight(＜15 kg)children presents significant clinical challenges due to their delicate vas-cular structures,limited surgical space,and complex perioperative management.This report presents two cases of kidney transplantation in low-age,low-weight children performed at Peking University People's Hospital.Case 1:a 2-year-3-month-old boy(8.8 kg),presenting a preoperative serum creatinine of 248μmol/L post-dialysis and the estimated glomerular filtration rates(eGFR)of 35.17 mL/(min·1.73 m2).Case 2:a 3-year-8-month-old girl(11.25 kg),presenting a preoperative creatinine of 281 μmol/L post-dialysis and the eGFR of 22.63 mL/(min·1.73 m2).Both recipients underwent transplantation via the extraperitoneal approach,with end-to-side anastomosis of the donor renal artery and vein to the recipient's common iliac artery and vein,respectively.The ureters were anastomosed to the bladder using the tunnel technique,and double-J stents were placed intraoperatively.The surgeries were uneventful,and both pa-tients exhibited rapid recovery of renal function.Postoperatively,serum creatinine levels decreased to 26μmol/L(Case 1)and 39 μmol/L(Case 2)by the third day,with the eGFR reaching 245.23 mL/(min·1.73 m2)and 164.12 mL/(min·1.73 m2),respectively.No complications,such as vascular thrombosis,ureteral stenosis,or abdominal compartment syndrome were observed during follow-up.A comprehensive literature review was conducted to contextualize these cases within global advancements in pediatric renal transplantation.Current evidence highlights the growing adoption of kidney transplantation for low-age,low-weight children,though debates persist regarding optimal surgical strategies(specifical-ly,the intraperitoneal versus extraperitoneal approaches).This case report underscores the feasibility of the extraperitoneal approach in overcoming anatomical limitations of low-weight pediatric recipients,with distinct advantages including reduced gastrointestinal complications and enhanced accessibility for post-operative ultrasound monitoring.Furthermore,mean arterial pressure(MAP)and central venous pressure(C VP)were systematically monitored intraoperatively to ensure optimal renal blood perfusion and graft viability.Our single-center experience provides valuable insights into surgical strategy selection and peri-operative management for this high-risk population.Nevertheless,larger multicenter studies are warranted to validate long-term outcomes and refine standardized protocols.

BACKGROUND:Unilateral knee osteoarthritis patients experience abnormal alterations in lower extremity gait biomechanics,yet few studies have analyzed changes in gait dynamics and muscle activation in knee osteoarthritis patients from the perspective of gait asymmetry.OBJECTIVE:To explore the effects of unilateral knee osteoarthritis on gait dynamics and muscle activation asymmetry in elderly women.METHODS:Thirty female patients with unilateral knee osteoarthritis attending Beijing Jishuitan Hospital Guizhou Hospital from October 2023 to March 2024 were selected as the knee osteoarthritis group,and 30 healthy elderly females without musculoskeletal disorders from the neighboring community were recruited as the control group.The kinetic and muscle activation levels of the subjects in both groups during walking were synchronously collected by a P-6000 force platform and a Free EMG300 surface EMG device.Kinetic parameters included the first and second peak forces of vertical ground reaction force.Muscle activation indexes included normalized root mean square values of rectus femoris,long head of biceps femoris,and lateral gastrocnemius muscle during the braking and pushing phases.Asymmetry index of the kinetic and muscle activation indexes were calculated separately in patients with K-L grade Ⅱ and Ⅲ knee osteoarthritis and controls and compared between groups by independent samples t-test and one-way analysis of variance.RESULTS AND CONCLUSION:(1)The difference between the second peak of vertical ground reaction force of both limbs in the knee osteoarthritis group was statistically significant(P＜0.05),as well as the difference between the standardized root mean square of rectus femoris in the braking phase and gastrocnemius and biceps femoris in the pushing phase(P＜0.05).(2)In terms of asymmetry index,the difference between the asymmetry index values of the first peak of vertical ground reaction force between the two groups of subjects was not statistically significant(P＞0.05),while the difference between the second peak asymmetry index values was statistically significant(P＜0.05).The difference in asymmetry index values of standardized root mean square of rectus femoris muscle during the braking phase as well as gastrocnemius and biceps femoris muscles during the pushing phase was statistically significant between the two groups of subjects(P＜0.05).(3)The asymmetry index of the standardized root mean square values of the second peak of vertical ground reaction force,rectus femoris in the braking phase,gastrocnemius in the pushing phase,and biceps femoris in the osteoarthritis group of the knee with K-L classification grade Ⅱand Ⅲ were significantly higher than those of the control group(P＜0.05).The asymmetry indices of standardized root mean square values of the second peak of vertical ground reaction force,rectus femoris in the braking phase and biceps femoris in the pushing phase were higher in the osteoarthritis group of the knee with K-L classification Ⅲ than in the osteoarthritis group of the knee with classification Ⅱ(P＜0.05).(4)The asymmetry indices of the second peak of vertical ground reaction,the rectus femoris muscle in the braking phase,and the muscle activation of the biceps femoris and gastrocnemius muscles in the pushing phase can be used as an important index for identifying gait asymmetry in the knee osteoarthritis,which is helpful in providing a theoretical basis for the development of rehabilitation treatment programs.It is also worth noting that extra attention should be paid to patients with higher severity of knee osteoarthritis in the clinical monitoring of gait asymmetry.