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

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.

Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus.Disorders in this process are tightly asso-ciated with adverse pregnancy outcomes including recurrent miscarriage (RM).However,an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking.In this study,we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unex-plained RM pregnancies at the early stage of gestation.Integrative analysis identifies 22 distinct cell clusters in total,and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed.Specifically,the cytotoxic properties of CD8+ effector T cells,nature killer(NK),and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status,and the population proportions and ligand-receptor interac-tions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients.The molecular features,spatial distribution,and the developmental trajectories of five decidual NK(dNK) subsets have been elaborately illustrated.In RM patients,a dNK subset that supports embryonic growth is diminished in proportion,while the ratio of another dNK subset with cyto-toxic and immune-active signature is significantly increased.Notably,a unique pro-inflammatory CD56 + CD16 + dNK subset substantially accumulates in RM decidua.These findings reveal a com-prehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

Objective To investigate the effects of interferon alpha?2b(IFNα?2b)on serum Hepcidin in hepatitis C patients and its mechanism. Methods Hepatitis C patients were divided evenly into treatment group and control group according to whether they had received treatment with IFNα?2b in the past 3 months. The serum hepci?din was compared between the two groups. HepG2 cells and LO2 cells were treated for 24 hours at varied levels of IFNα?2b(0,50,100,200,400μL)and real?time PCR was used to detect the hepcidin,interleukin?6(IL?6)and signal transduction and transcription activator 3(STAT3)mRNA expression of cells. The protein levels of STAT3 and phosphorylated STAT3(pSTAT3)were measured by Western blot. The changes of these indexes were observed with the gradual increase of IFNα?2b levels. Results Serum Hepcidin level in the treatment group was significantly lower than the control(P<0.05). IFNα?2b inhibited the Hepcidin mRNA in HepG2 cells and LO2 cells. pSTAT3 was significantly decreased with the increased levels of IFNα?2b(P<0.05),and the expression of IL?6 and STAT3 had no significant changes with the increase of IFNα?2b. Conclusion The serum Hepcidin levels can be decreased because IFNα?2b suppresses the expression of Hepcidin,and its mechanism may be related with inhibited STAT3 pathway activation.

OBJECTIVETo generate mice which are specific for peroxisomproliferator-activated receptor-γ coactivator-1(PGC-1α) knockout in the GABAergic interneuron.

METHODSConditional mice specific for PGC-1αwere introduced from the Jackson Laboratory, USA and initially inbred to obtain homozygote PGC-1αmice. The PGC-1αconditional mice were further crossed with Dlx5/6-Cre-IRES-EGFP transgenic mice to achieve specific knockout of PGC-1α in the GABAergic interneuron.

RESULTSThe offspring with specific knockout PGC-1α gene were successful for the generation of GABAergic interneuron, with the resulting genotype being PGC-1α.

CONCLUSIONThe PGC-1αmice were obtained through a proper crossing strategy, which has provided a suitable platform for studying the function of PGC-1α in neuropsychiatric diseases.

Animals ; Female ; Humans ; Interneurons ; metabolism ; Male ; Mice ; Mice, Knockout ; Neurodegenerative Diseases ; genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; genetics ; gamma-Aminobutyric Acid ; metabolism

Objective To investigate the correlations between occupational stress and care ability of nurses in operating room.Method Occupational stress scale and caring ability evaluation scale were used for the investigation among 180 nurses in 4 general hospitals in Beijing.Results Occupational stress scale (405.61±27.44) and nurses' operating ability (189.07±16.82) in the operating rooms were negatively correlated (P ＜0.05).The occupational stress was negatively correlated with caring ability of the nurses from the operating room.Conclusions Occupational stress of the nurses from the operating room is at the middle level.The care ability is low generally.The occupational stress of the nurses in the operating room is lower and the care ability is higher.Nurse manager can create good working environment,streathing human resource magement to reduce nurse's working stress,thus increase working quality.

Objective To investigate the influence of miR-106b on Wnt/β-catenin pathway in HCC cells. Methods QGY-7703 and HepG2 cells were transfected with miRNA mimics or inhibitors. TOP/FOP luciferase ratio assay was used to test the Wnt/β-catenin pathway activity. The expression of downstream targeted genes of Wnt/β-catenin pathway were examined by Real-time PCR. The accumulation of β-catenin in nuclears were measured by Western blotting. Results Ectopic expression of miR-106b dramatically increased the average TOP/FOP ratio and the mRNA expression of downstream targeted genes in QGY-7703 and HepG2 cells. Compared with that in control cells , miR-106b over-expression promoted the nuclear β-catenin accumulation in QGY-7703 cells. Clonclusion MiR-106b activated Wnt/β-catenin pathway in HCC cells.

Objective:To explore the expression of aquaporin1 (AQP1) in human glioma tissues and its relationship with the clini-copathological parameters and prognosis of this tumor. This study also observed the function of AQP1 in the proliferation and invasion of LN229 glioblastoma cells. Methods:The expression of AQP1 in 135 cases of glioma was detected by immunohistochemical meth-od, and the correlation between AQP1 and pathological features of glioma was analyzed. The relationship of AQP1 with survival was al-so investigated using 103 specimens with complete clinical data. AQP1 was successfully transfected into LN229 cells with lentiviral vector, and the expression of AQP1 protein was tested by Western blot. Cell proliferation was detected by using methyl thiazolyl tetrazo-lium assay, whereas cell invasion was determined by Transwell assay. Results:The expression of AQP1 was positively correlated with pathological grading. High AQP1 expression was associated with poor prognosis (P<0.05). Moreover, the overexpression of AQP1 can significantly increase the proliferation and invasion of LN229 cells (P<0.05). Conclusion:AQP1 is closely associated with the progres-sion of glioma. Upregulation of the AQP1 expression promoted the proliferation and metastasis of glioma cells. These findings indicat-ed that AQP1 can function as a therapeutic target for glioma in future research.

This article analyzed the current problems existing in the public health master cur-ricula system, such as educational ideas being backward, tralning objectives not explicit, curricula teaching unsatisfactory and effects of practical curriculum needing to be improved. Based on the pro-fessional competencies, we discussed the ideas and principles of the new curricula system of master of public health, and proposed making sure of a refined professional competencies, making strict traln-ing standards, confirming tralning objectives, embodying advantages, setting up reasonable curricula, fostering practical abilities, strengthening cooperation and carrying on professional identification.