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 relationship between serum complement levels at diagnosis and prognosis in patients with aggressive non-Hodgkin lymphoma(NHL). METHODS: The clinical data of 102 patients with aggressive non-Hodgkin lymphoma diagnosed in the First Hospital of Lanzhou University from February 2017 to March 2023 were selected to analyze the correlation between serum complement C3 and C4 levels and prognosis of patients with aggressive NHL at the time of initial diagnosis. The optimal cut-off point of C3 and C4 were obtained by calculating the Jorden index through the receiver operating characteristic（ROC） curve, and 102 patients were divided into low C3 group (C3< 1.07) and high C3 group (C3≥1.07), low C4 group (C4< 0.255) and high C4 group (C4≥0.255). The effects of serum C3 and C4 levels on the prognosis of these patients were analyzed. RESULTS: ROC curve analysis showed that the area under the curve (AUC) of C3 and C4 in predicting the prognosis of aggressive NHL patients was 0.634 (95%CI ：0.525-0.743；P =0.025) and 0.651 (95%CI ：0.541-0.761；P =0.012), respectively. The optimal cut-off points for C3 and C4 were 1.07 and 0.255, respectively. K-M survival analysis showed that groups with high C3 and C4 levels had shorter progression-free survival (PFS) (P =0.0079; P =0.0092) and overall survival (OS) (P =0.021; P =0.021). Multivariate Cox analysis showed that high level serum complement C3 (HR=2.37, 95%CI : 1.07-5.24, P =0.034) and age ≥60 years (HR=2.34, 95%CI : 1.11-4.95, P =0.025) were independent risk factors for PFS in patients with aggressive NHL. High level complement C3 (HR=2.37, 95%CI : 1.09-5.13, P =0.029) and age ≥60 years at diagnosis (HR=2.40, 95%CI : 1.13-5.13, P =0.024) were independent risk factors for OS in patients with aggressive NHL. CONCLUSION The level of serum complement C3 at diagnosis is one of the prognostic factors in patients with aggressive NHL.
Humans ; Lymphoma, Non-Hodgkin/blood* ; Prognosis ; Complement C3/metabolism* ; Complement C4/metabolism* ; ROC Curve ; Male ; Female ; Middle Aged ; Adult ; Aged

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To compare the clinical characteristics of diabetes mellitus(DM)patients complicated with pyogenic liver abscess(PLA)and non-DM(NDM)patients complicated with PLA,and provide evidence for clinical diagnosis and treatment.Methods PLA patients who admitted to an affiliated hospital of Anhui Medical University from July 2002 to February 2022 were selected and divided into DM+PLA group and NDM+PLA group according to whether they had DM.General condition,clinical manifestations and signs.complications,biochemical and patho-genic examination results,imaging findings,as well as clinical efficacy and influencing factors of the two groups of patients were analyzed retrospectively.Results 695 PLA patients were included in the analysis,191(27.5％)in the DM+PLA group and 504(72.5％)in the NDM+PLA group.The proportions of males and complication of hypertension in the DM+PLA group were higher than those in the NDM+PLA group,while the proportion of bi-liary diseases and malignant tumors was lower(all P＜0.05).The proportions of patients developing fever,fa-tigue,as well as concurrent anemia and hypoalbuminemia in the DM+PLA group were higher than those in the NDM+PLA group(all P＜0.05).Compared with the NDM+PLA group,the neutrophil count and percentage in the DM+PLA group increased,while total protein,albumin content,and albumin/globulin ratio all decreased(all P＜0.05).The proportions of the detection of Klebsiella pneumoniae and the occurrence of liver right lobe abscess in DM+PLA patients were higher than those of the NDM+PLA group(both P＜0.05).Multivariate logistic re-gression analysis revealed that malignant tumor was a risk factor for affecting the clinical efficacy of PLA patients,invasive treatment was a protect factor for affecting the clinical efficacy of PLA patients,while blood sugar was a risk factor for affecting the clinical efficacy of NDM+PLA patients.Conclusion DM+PLA patients have more se-vere infection symptoms than NDM+PLA patients,and are accompanied by higher proportions of Klebsiella pneu-moniae infection and liver right lobe abscess.It is necessary to strengthen attention to patients with malignant tumor and control blood sugar level,and timely supplement with invasive treatment if necessary.

Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P＜0.05).There was no significant differences in postoperative drainage between the two groups(P＞0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)％vs(12.1±1.5)％]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)％vs(66.3±8.2)％]were significantly different(P＜0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P＞0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P＞0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)％vs(18.4±2.4)％]and at the last follow-up[(9.8±1.6)％vs(12.1±1.5)％](P＜0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P＜0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P＜0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P＜0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P＜0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.

Objective To explore the effect and mechanism of hydroxysafflor yellow A(HSYA)on autophagy in bEnd.3 cells after oxygen-glucose deprivation(OGD).Methods The bEnd.3 cells were divided into normal group(conventional culture),model group(OGD model),HSYA group(OGD model+75 μmol·L-1 HSYA),3-methyladenine(3MA)group(5 mmol·L-1 3MA+OGD model)and 3 MA+HSYA group(5 mmol·L-1 3 MA+OGD model+75 μmol·L-1 HSYA).The level of apoptosis was determined by TUNEL fluorescence staining;Western blot was used to detect the expression of autophagy,blood brain barrier(BBB)related proteins;real time fluorescence quantitative polymerase chain reaction method for determining the expression of sirtuin-1(SIRT1)and forkhead box protein O3a(FOXO3A)mRNA.Results In the normal group,model group,HSYA group,3MA group and 3MA+HSYA group,the positive cells selected for TUNEL staining were 5.00±1.00,28.00±2.00,21.00±3.00,35.33±2.51 and 29.67±2.52;the expression levels of microtubule-associated protein 1 light chain 3-Ⅱ/-Ⅰ(LC3-Ⅱ/-Ⅰ)were 0.90±0.20,1.34±0.10,1.95±0.14,0.76±0.15 and 1.14±0.09;sequestosome 1(P62)were 0.99±0.02,0.60±0.02,0.38±0.01,0.67±0.04 and 0.54±0.01;occludin were 1.39±0.17,0.62±0.15,1.00±0.09,0.40±0.13 and 0.80±0.15;zonula occludens-1(ZO-1)were 1.63±0.20,0.64±0.06,0.98±0.14,0.37±0.14 and 0.87±0.04;SIRT1 mRNA were 1.00±0.00,0.75±0.07,1.69±0.09,0.31±0.02 and 0.56±0.01;FOXO3A mRNA were 1.00±0.00,0.80±0.05,1.47±0.09,0.40±0.01 and 0.62±0.09,respectively.Significant differences were found between model group and normal group,HSYA group and model group,3MA+HSYA group and 3MA group(P＜0.05,P＜0.01,P＜0.001).Conclusion HSYA may enhance autophagy levels in bEnd.3 cells after OGD through the SIRT1/FOXO3A pathway,inhibit cell apoptosis and alleviate BBB damage.

OBJECTIVE: To investigate the efficacy of posterior three-columns osteotomy in the treatment of severe tuberculous angular kyphosis. METHODS: Total of 33 patients with severe tuberculous angular kyphosis were treated with posterior three-columns osteotomy from January 2006 to January 2019 including 24 males and 9 females with an average age of (40.6±23.3) years old ranging from 15 to 62 years old and an average disease duration of (23.5±15.5) years ranging from 4 to 40 years. The Cobb's angle of kyphosis was (118.65±28.82)°. Interradicular bone-disc-bone osteotomy(BDBO), posterior-only vertebral column resection (PVCR) and posterior multilevel vertebral osteotomy (PMVO) were performed to correct spinal deformity individually. The visual analogue scale (VAS), Oswestry disability index (ODI), sagittal vertical axis (SVA), ASIA spinal cord functional classification and motor function score, and deformity correction rate were measured and statistically analyzed before, after and at the final follow-up. RESULTS: Total of 33 patients were followed up from 15 to 96 months with an average of (38.00±6.38) months. The last follow-up of kyphosis Cobb angle (23.88±5.45)° showed no significant loss from postoperative 12 months (20.40±9.13)°, P>0.05. The SVA, VAS, ODI and ASIA spinal cord functional classification and motor function score were significantly improved at 1 year and last follow-up after operation(P<0.01). The fusion time of the osteotomy site was (18.50±5.16) months. The ASIA classification of 15 patients with spinal cord injury were improved by at least 2 grades after operation, and their daily life and work ability were various levels of restored. Postoperative complications of spinal cord injury occurred in 3 cases. CONCLUSION Posterior three-columns osteotomy is the most effective method for the treatment of angular kyphosis of spinal tuberculosis.Careful preoperative design and individualized osteotomy can not only correct the deformity, but also a successful decompression to the spinal cord and promote the recovery of spinal cord function.
Humans ; Male ; Female ; Osteotomy/methods* ; Kyphosis/surgery* ; Adult ; Adolescent ; Middle Aged ; Young Adult ; Tuberculosis, Spinal/complications* ; Treatment Outcome

ObjectiveTo observe the impacts of electroacupuncture （EA） on the expression of hippocampal brain-derived neurotrophic factor （BDNF） and acetylated histone （AcH3） in the rat model of spared nerve injury （SNI）， so as to explore the analgesic and antidepressant effects of EA. MethodsTwenty-four Male SD rats were randomly divided into 4 groups， with 6 in each group. SNI was used to establish the model of pain and depression. All the groups were intervened one week after SNI surgery and persisted 5 weeks. The EA group was treated with EA （2 Hz） for 30 min every other day and imipramine drug group （IMP） group with peritoneal imipramine injection （10 mg/kg） per day. The sham surgery group （SS） and model group （SNI） received the same grasping stimulation. The paw mechanical withdrawal threshold （PWT） test was performed before the SNI surgery， 1， 2， 3， 4， 5， and 6 weeks after surgery， respectively. The forced swimming test （FST） and the sucrose preference test （SPT） were performed 6 weeks after SNI surgery. The Western blot method was employed to detect the expression of BDNF and AcH3 from the rat hippocampal tissue at the end of the behavioral tests. ResultsCompared with the SS group， the SNI group had significantly decreased PWT and sucrose consumption， prolonged FST immobility time （all P<0.01）， down-regulated BDNF and AcH3 expression （P<0.05 & P<0.01） in the hippocampus， which indicated the successful construction of the pain-depression model. Compared with the SNI group， 6 weeks after SNI surgery， the EA and IMP groups had significantly increased PWT and sucrose consumption， and reduced FST immobility time （all P<0.01）； the EA group had up-regulated BDNF and AcH3 expression （both P<0.05） in the hippocampus， the IMP group had up-regulated AcH3 （P<0.05） expression but no difference in BDNF expression. ConclusionEA could relieve pain and depressive behavioral symptoms in SNI rats. And its analgesic and antidepressant mechanisms may relate to the up-regulation of hippocampal AcH3 and BDNF expression.

Objective:To investigate the effect of intravenous anesthesia on the detection rate of lesions in diagnostic gastroscopy.Methods:A total of 9 071 subjects who underwent diagnostic gastroscopy at the Digestive Endoscopy Center of Yangzhou University Affiliated Hospital from March 2021 to February 2022 were selected. Data were collected from the gastroscopy quality control system, including age, gender, examination physician, Helicobacter pylori infection, examination method, withdrawal time, number of images left, number of biopsies, biopsy site, gastroscopy diagnosis, pathological diagnosis, etc. They were divided into anesthesia group and general group based on the examination method, and propensity score matching (PSM) was performed on the two groups of subjects. Excluding confounding factors, the detection of lesion location and lesion type in two groups of subjects was analyzed; Simultaneously, univariate and multivariate logistic regression analysis was used to analyze the influencing factors of the detection rate of precancerous lesions and malignant tumors in the upper gastrointestinal tract.Results:After PSM, 1 655 subjects were included in both groups. In terms of lesion location, the detection rate of gastric body lesions in the anesthesia group was higher than that in the general group ( P<0.05), and the detection rate of esophageal lesions in the anesthesia group was lower than that in the general group ( P<0.05); In terms of lesion types, the detection rate of precancerous lesions such as gastric polyps, mucosal protrusions, mucosal atrophy, and intestinal metaplasia in the anesthesia group was higher than that in the general group (all P<0.05). The results of logistic regression analysis showed that intravenous anesthesia was an independent influencing factor for the detection rate of precancerous lesions and malignant tumors in diagnostic gastroscopy ( OR=1.338, 95% CI: 1.070-1.674, P<0.05). Conclusions:Intravenous anesthesia is an independent influencing factor for the detection rate of precancerous lesions and malignant tumors in diagnostic gastroscopy, and can improve the detection rate of upper gastrointestinal lesions.