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 optimize the optimum processing technology of vinegar-processed Artemisiae Argyi Folium(AAF),and analyze the difference of index components and analgesic activity before and after processing.METHODS The method for the determination of total flavonoids and total terpenes in AAF was established with eupatilin and Santamarine as control substances,re-spectively.The HPLC-VWD method was established for the simultaneous determination of 6-Methoxytricin,Santamarine,eupatilin and Artemisolide in AAF.Box-Behnken design-response surface method was used to optimize the processing technology of vinegar-processed AAF,with the content of total flavonoids,total terpenes and four active ingredients as the index,and the amount of rice vin-egar,moistening time,processing temperature and processing time as the factors.The quantitative analysis was combined with hierar-chical cluster analysis(HCA),principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)to evaluate the difference of index components before and after processing.The analgesic activity before and after processing was investigated using pain mice induced by formalin.RESULTS The optimum processing parameters of vinegar-processed AAF were 16%rice vinegar dosage,moistening time 50 min,processing temperature 160℃and processing time 12 min.There were significant differences in the content of index components before and after processing.The analgesic activity of vinegar-processed AAF was signifi-cantly better than that of AAF.CONCLUSION The optimized processing technology is stable and feasible,which can provide scien-tific basis for standardizing production of vinegar-processed AAF.

Cerebral proliferative angiopathy(CPA)was initially regarded as a variant of arteriovenous malformation.However,its distinct histological,angiographic,and pathophysiological features have led to its reclassification as an independent entity.CPA is an exceptionally rare form of cerebral vascular malformation,its pathogenesis is primarily linked to diffuse vascular proliferation secondary to chronic hypoperfusion.Clinically,CPA presents with a heterogeneous spectrum of manifestations,most commonly severe headaches and epileptic seizures.Neuroimaging(MR)typically reveals a complex interplay of aberrant vessels within the brain parenchyma,which may complicate the clinical management and lead to a higher rate of poor prognosis.This article reviewed current knowledge on the pathogenesis,epidemiology,clinical features,diagnostic approaches,and treatment options for CPA,with the aim of enhancing understanding of its underlying mechanisms and guiding future therapeutic strategy optimizations.

BACKGROUND:In recent years,the use of blood flow restriction training in the rehabilitation of ankle injuries has gradually increased,and this technique can improve muscle strength,and can achieve a similar effect of high-load resistance training when combined with low-intensity resistance training. OBJECTIVE:To elucidate the current application status of blood flow restriction training in the prevention and rehabilitation of foot and ankle injuries. METHODS:A literature search was conducted on CNKI,PubMed,and Web of Science databases. The Chinese search terms were "blood flow restriction training,pressure training,ankle,ankle joint," and the English search terms were "blood flow restriction,BFR,KAATSU,ankle,foot." Relevant literature from database inception to July 2023 was retrieved,and 50 articles were ultimately included according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:In foot and ankle applications,blood flow restriction training is primarily used in studies of Achilles tendon thickness and ankle muscle strength in healthy individuals,as well as in chronic ankle instability,after Achilles tendon ruptures,and after external ankle fractures. Single blood flow restriction training can reduce the thickness of Achilles tendon in healthy individuals,while long-term training can make it thicker. Blood flow restriction training can prevent muscle strength decline in healthy individuals,while low-intensity blood flow training can promote ankle muscle strength recovery in injured patients. In current research,few adverse events related to blood flow restriction have been found,and future research should compare the efficacy of different training programs in different populations and optimize the research content.