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 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

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.

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.

During long-duration space missions,astronauts face health challenges such as bone density loss,muscle atrophy,cardiovascular dysfunction,immune function suppression caused by microgravity,as well as mental health issues in a confined environment.There is an urgent need for real-time,continuous,and multi-dimensional health monitoring technologies to safeguard the health and safety of astronauts.This paper systematically reviews the technical requirements and current development status of astronaut on-orbit health monitoring,with a focus on analyzing breakthroughs in technologies such as dynamic electrocardiography,non-invasive blood pressure assessment,flexible electronic skin,and molecular probe spectroscopy.It also elaborates on how the integration of artificial intelligence and bionics technologies is propelling the monitoring system towards intelligence and autonomy,providing a reference for the medical support of astronauts during long-duration spaceflight missions.

Background Non-suicidal self-injury(NSSI)behavior has become a major public health concern and can have significant implications for the physical and mental health of adolescents.Peer victimization is a risk factor for adolesents to have NSSI behavior,so exploring the relationship and underlying mechanism between peer victimization and NSSI functions will provide a promising strategy for the prevention and intervention of NSSI behavior.Objective To investigate the relationship between peer victimization and NSSI functions in adolescents with unipolar and bipolar depression,so as to provide references for the intervention of NSSI behavior in adolescent patients with unipolar and bipolar depression.Methods Using multi-stage stratified sampling,940 adolescents with unipolar and bipolar depression who met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)criteria for bipolar depressive episodes or depressive disorders were selected from 14 psychiatric hospitals in China.All participations were assessed using Chinese version of the Functional Assessment of Self-Mutilation(C-FASM),Multidimensional Peer-Victimization Scale(MPVS),UCLA Loneliness Scale(UCLA-LS)and Patient Health Questionnaire-9 item(PHQ-9).Pearson correlation coefficient was to assess the correlation among above scales,and the model fit and path coefficients for mediation were analyzed with model 4 in Process 4.0 for SPSS.Results A total of 698(74.26%)adolescents with unipolar and bipolar depression completed the questionnaire survey.NSSI behavior was detected in 374 patients(53.58%).Among adolescents with unipolar and bipolar depression and NSSI behavior,MPVS total score was positively correlated with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.104,0.130,0.266,P<0.05 or 0.01),UCLA-LS score also yielded a positive correlation with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.321,0.112,0.246,P<0.05 or 0.01),and UCLA-LS score was positively correlated with MPVS total score(r=0.241,P<0.01).Loneliness demonstrated a complete mediating role in the relationship between peer victimization and emotion regulation function,with an indirect effect value of 0.033(95%CI:0.019～0.050)and an effect size of 73.33%.A partial mediating effect of loneliness was also observed for the relationship between peer victimization and social avoidance function,with an indirect effect value of 0.016(95%CI:0.007～0.025)and an effect size of 17.98%.Conclusion Loneliness may act as a mediator in the relationship between the peer victimization and the NISS emotion regulation and social avoidance functions in adolescents with unipolar and bipolar depression and NSSI behaviors.

Gold nanoparticles(AuNPs)present unique physicochemical characteristics,excellent biocom-patibility and ease of surface functionalization,which have become the research hotspots in the field of biosens-ing.This article reviews the synthesis methods,main properties and surface functionalization of AuNPs,as well as the research progress of application in various sensing platforms.

Objective:To analyze the preoperative and postoperative serum cholinesterase (CHE) levels in patients with stage ⅠA-ⅢA breast cancer who underwent surgical treatment, and to explore the roles of them and peripheral blood inflammatory markers in the prognostic prediction of stage ⅠA-ⅢA breast cancer.Methods:The relevant blood indicators of 152 patients with stage ⅠA-ⅢA breast cancer who underwent surgery and postoperative adjuvant therapy from January 2012 to December 2017 at Affiliated Huai'an Hospital of Xuzhou Medical University were retrospectively studied. The optimal cut-off values of serum CHE levels and peripheral blood inflammatory markers [systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) ] were calculated using X-tile 3.6.1 software. Patients were categorized into low and high value groups based on the optimal cutoff values. Kaplan-Meier curves and Cox regression analysis were used to assess the correlation between CHE and peripheral blood inflammation indexes and disease-free survival (DFS). Spearman correlation coefficient and Wilcoxon test were used to assess the correlation and changes of CHE and inflammation indexes before and after treatment. In addition to this, a nomogram prediction model was conscturcted based on independent prognostic factors by R software, which was validated by Bootstrap method.Results:The CHE levels of patients before and after treatment was 8 645.0 (7 251.3, 10 229.3) and 9 309.0 (7 801.0, 10 835.3) U/L, respectively, with a statistically significant difference ( Z=2.73, P=0.006) .The optimal cut-off values for postoperative CHE (Post-CHE), postoperative SII (Post-SII), and postoperative SIRI (Post-SIRI) associated with patients' DFS, being 7 773 U/L, 741, and 0.9, respectively. Univariate analysis showed that tumor size (≤2 cm vs.>2 cm and ≤5 cm: HR=2.55, 95% CI: 1.30-4.99, P=0.006; ≤2 cm vs. >5 cm: HR=8.95, 95% CI: 4.15-19.32, P<0.001), number of positive lymph nodes ( HR=3.84, 95% CI: 2.24-6.58, P<0.001), clinical stage (stage Ⅰ vs. stage Ⅱ: HR=1.52, 95% CI: 0.68-3.39, P=0.309, stage Ⅰ vs. stage Ⅲ: HR=8.12, 95% CI: 3.76-17.55, P<0.001), Ki-67 expression ( HR=2.19, 95% CI: 1.24-3.84, P=0.007), whether radiotherapy ( HR=2.05, 95% CI: 1.19-3.53, P=0.010), Post-CHE ( HR=6.81, 95% CI: 3.94-11.76, P<0.001), Pre-neutrophil to lymphocyte ratio (NLR) ( HR=1.11, 95% CI: 1.02-1.21, P=0.014), Post-NLR ( HR=5.23, 95% CI: 2.78-9.85, P<0.001), Pre-platelet to lymphocyte ratio (PLR) ( HR=2.08, 95% CI: 1.01-4.26, P=0.046), Post-PLR ( HR=7.11, 95% CI: 3.78-13.37, P<0.001), Pre-lymphocyte to monocyte ratio (LMR) ( HR=0.37, 95% CI: 0.20-0.66, P<0.001), Post-LMR ( HR=0.23, 95% CI: 0.13-0.41, P<0.001), Pre-SII ( HR=1.81, 95% CI: 1.05-3.12, P=0.033), Post-SII ( HR=6.12, 95% CI: 3.48-10.76, P<0.001), Pre-SIRI ( HR=2.12, 95% CI: 1.24-3.63, P=0.006), and Post-SIRI ( HR=4.93, 95% CI: 2.87-8.48, P<0.001) were associated with DFS in patients with stage ⅠA-ⅢA breast cancer. Multivariate analysis showed that tumor size (≤2 cm vs. >2 cm and ≤5 cm: HR=2.86, 95% CI: 1.41-5.78, P=0.003; ≤2 cm vs. >5 cm: HR=3.72, 95% CI: 1.50-9.26, P=0.005), number of positive lymph nodes ( HR=4.66, 95% CI: 2.28-9.54, P<0.001), Ki-67 expression ( HR=2.13, 95% CI: 1.15-3.94, P=0.016), Post-CHE ( HR=0.18, 95% CI: 0.10-0.33, P<0.001), Post-SII ( HR=2.71, 95% CI: 1.39-5.29, P=0.004), and Post-SIRI ( HR=3.77, 95% CI: 1.93-7.36, P<0.001) were independent influencing factors for DFS in patients with stage ⅠA-ⅢA breast cancer. Kaplan-Meier survival curve analysis showed that the median DFS of patients in the Ki-67<30% group was not reached, and the median DFS of patients in the Ki-67≥30% group was 89.0 months, and the 3- and 5-year DFS rates were 84.9% vs. 75.9% and 80.8% vs. 64.3%, respectively, with a statistically significant difference ( χ2=7.65, P=0.006) ; the median DFS of patients in the tumor size≤2 cm group was not reached, the median DFS of the 2 cm5 cm group was 26.3 months, and the 3- and 5-year DFS rates were 95.5% vs. 74.6% vs. 42.1%, 86.3% vs. 68.6% vs. 25.3%, with a statistically significant difference ( χ2=40.46, P<0.001) ; the median DFS of patients in the group with the number of positive lymph nodes<4 was not reached, and the median DFS of the group with the number of positive lymph nodes≥4 was 30.7 months, and the 3- and 5-year DFS rates were 87.9% vs. 46.4% and 81.4% vs. 28.6%, respectively, with a statistically significant difference ( χ2= 47.34, P<0.001) ; the median DFS of patients in the Post-CHE<7 773 U/L group was 47.3 months, and the median DFS of patients in the Post-CHE≥7 773 U/L group was not reached, and the 3- and 5-year DFS rates were 52.8 % vs. 88.6% and 27.8% vs. 81.2%, respectively, with a statistically significant difference ( χ2=62.17, P<0.001) ; the median DFS was not achieved in patients in the Post-SII<741 group, and the median DFS was 30.5 months in the Post-SII≥741 group, with 3- and 5-year DFS rates of 88.1% vs. 38.5% and 80.1% vs. 30.8%, respectively, with a statistically significant difference ( χ2=50.78, P<0.001) ; the median DFS of patients in Post-SIRI<0.9 group was not reached, the median DFS of Post-SIRI≥0.9 group was 33.3 months, and the 3- and 5-year DFS rates were 93.5% vs. 46.7% and 84.9% vs. 39.9%, respectively, with a statistically significant difference ( χ2=40.67, P<0.001). Spearman correlation analysis revealed that Post-CHE was not correlated with Post-SII ( r=-0.111, P=0.175), and Post-CHE was negatively correlated with Post-SIRI ( r=-0.228, P=0.005). Post-treatment CHE was elevated compared to preoperative and the median DFS was not reached in patients with elevated CHE group and 61.8 months in patients with reduced CHE group after treatment, with a statistically significant difference ( χ2=25.67, P<0.001). The nomogram based on independent prognostic factors had good predictive performance, with a C-index of 0.893. Conclusion:The serum CHE level exhibited a significant increase following treatment. Postoperative serum CHE combined with SII and SIRI can effectively predict DFS in patients with stage ⅠA-ⅢA breast cancer, and the prognosis of patients with elevated CHE after treatment is better. The nomogram constructed based on independent prognostic factors has good predictive performance for DFS in breast cancer patients.