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.

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

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.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.