Objective:To investigate the differences in programmed death-ligand 1 (PD-L1) expression and immune cell infiltration characteristics in different molecular subtypes of endometrial cancer.Methods:A retrospective case series study was conducted. Ninety primary treated EC patients who underwent surgery without preoperative neoadjuvant therapy at the Second Hospital of Tianjin Medical University from November 2016 to May 2022 were collected. The surgical paraffin-embedded tissues were selected, and the molecular subtypes of endometrial cancer were classified according to 2020 World Health Organization (WHO) molecular subtypes using POLE gene Sanger sequencing and immunohistochemical staining. The expression of PD-L1, CD3, CD4, CD8, CD68, and CD20 proteins were detected by immunohistochemistry. Stained slides were digitally scanned for quantitative analysis of PD-L1 and immune cell infiltration density. The PD-L1-related scores were evaluated, including tumor cell score (TCS, the percentage of PD-L1 positive tumor cells among total tumor cells ≥1% was TCS positive, <1% was TCS negative), immune cell score (ICS, the percentage of PD-L1 positive tumor-associated lymphocytes and macrophages among total tumor-associated lymphocytes and macrophages ≥1% was ICS positive, <1% was ICS negative) and combined positive score [CPS, PD-L1 positive stained cells (including tumor cells, lymphocytes and macrophages)/total number of viable tumor cells ×100 ≥ 1 was CPS positive, < 1 was CPS negative]. Clinicopathological characteristics, PD-L1 scores and immune cell infiltration densities among different molecular subtypes were analyzed. Kaplan-Meier method was used to plot disease-free survival (DFS) curves for molecular subtypes, PD-L1 scores and immune cell infiltration densities, with subgroup comparisons using log-rank test. Cox proportional hazards models were used for univariate and multivariate analyses of poor DFS in endometrial cancer patients.Results:The median age of 90 patients was 58 years old (range: 33-72 years old); endometrioid carcinoma was present in 78 cases (86.7%), and non-endometrioid carcinoma was present in 12 cases (13.3%). Molecular subtyping identified POLE-mutated subtype in 6 cases (6.7%), mismatch repair deficient (MMRd) subtype in 23 cases (25.6%), p53 abnormal subtype in 14 cases (15.6%), and non-specific molecular profile (NSMP) subtype in 47 cases (52.2%). Significant differences were observed among the 4 molecular subtypes in International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, morphological subtype, tertiary lymphoid structures, estrogen receptor expression, and progesterone receptor expression (all P < 0.05). Among the 90 cases, 18 cases (20.0%) were positive for TCS, 31 cases (34.4%) were positive for ICS, and 39 cases (43.3%) were positive for CPS. Significant differences were found among the 4 molecular subtypes in PD-L1 + cell density, distribution of patients with ICS positivity, and distribution of patients with CPS positivity (all P < 0.01), but not in distribution of patients with TCS positivity ( P = 0.090); compared to NSMP subtype, the proportions of ICS-positive patients in POLE-mutated and MMRd subtypes were higher, the proportion of CPS-positive patients and PD-L1 + cell density in MMRd and p53 abnormal subtypes were higher, and the differences were statistically significant (all P < 0.05). Significant differences in immune cell densities were observed among the 4 molecular subtypes (all P < 0.01); compared to NSMP subtype, POLE-mutated, MMRd and p53 abnormal subtypes had higher densities of CD3 + and CD8 + cells, MMRd subtype had higher CD4 + cell density, and POLE-mutated and MMRd subtypes had higher CD68 + and CD20 + cell densities (all P < 0.05). The median follow-up was 43 months (range: 7-75 months). Among the molecular subtypes, p53 abnormal patients had the worst DFS, and POLE-mutated patients had the best DFS, and the difference in DFS among the 4 subtypes was statistically significant ( P = 0.046). Grouping according to the median density of immune cells in the entire group, patients with high CD8 + cell density (45 cases) had better DFS than those with low density (45 cases) ( P = 0.010), PD-L1 ICS-positive patients had worse DFS than negative patients ( P = 0.019), and NSMP subtype patients with high CD4 + cell density (24 cases) had better DFS than those with low density (23 cases) ( P < 0.001). There was no statistically significant difference in DFS among patients grouping with other PD-L1 scoring modes and other immune cell infiltration density (all P > 0.05). Cox regression analysis indicated that high CD8 + cell density ( HR = 0.335, 95% CI: 0.113-0.990, P = 0.048) was an independent protective factor for poor DFS in endometrial cancer patients, and high CD4 + cell density was an independent protective factor for poor DFS in NSMP subtype patients ( HR = 0.035, 95% CI: 0.003-0.345, P = 0.004). Conclusions:There are significant differences in PD-L1 expression and immune cell infiltration density among the different molecular subtypes of endometrial cancer, which are correlated with the prognosis of patients, and may provide reference for the selection of immunotherapy strategies and prognosis judgment.

OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on renal function after laparoscopic radical nephrectomy. METHODS: We reviewed the clinical data of 282 patients with renal cell carcinoma (RCC), who underwent laparoscopic radical nephrectomy (LRN) in the Department of Urology, Third Medical Center of PLA General Hospital from November, 2020 and June, 2022.According to whether DEX was used during the operation, the patients were divided into DEX group and control group, and after propensity score matching, 99 patients were finally enrolled in each group.The incidence of acute kidney injuries were compared between the two groups.Serum creatinine (sCr) data within 3 months to 1 year after the operation were available in 51 patients, including 26 in DEX group and 25 in the control group, and the incidence of chronic kidney disease (CKD) was compared between the two groups. RESULTS: After propensity score matching and adjustment for significant covariates, there were no significant differences in postoperative levels of sCr, cystatin C (CysC), β2-microglobulin (β2-MG), hemoglobin (Hb), or C-reactive protein (CRP), extubation time, incidence of AKI, or length of hospital stay between the two groups (P>0.05).The intraoperative urine volume was significantly higher in DEX group than in the control group (P < 0.05).A significant correlation between AKI and CKD was noted in the patients (P < 0.05).The incidence of CKD did not differ significantly between the two groups (P>0.05). CONCLUSION DEX can not reduce the incidence of AKI or CKD after LRN.
Humans ; Dexmedetomidine ; Incidence ; Propensity Score ; Renal Insufficiency, Chronic/epidemiology* ; Kidney Neoplasms/surgery* ; Nephrectomy/adverse effects* ; Laparoscopy/adverse effects* ; Acute Kidney Injury/prevention & control* ; Retrospective Studies

Objective:To explore the clinical features of acute pancreatitis (AP) complicated with portal vein system thrombosis (PVST) and the clinical prediction of symptomatic PVST.Methods:From January 2014 to December 2019, at First Affiliated Hospital and Second Affiliated Hospital of Kunming Medical University, 152 hospitalized patients who met the diagnostic criteria of AP complicated with PVST and had complete clinical data were retrospectively analyzed, and the clinical characteristics of them were analyzed. According to whether there were clinical manifestations caused by PVST (esophago-gastric variceal bleeding, persistent ascites, intestinal ischemia), AP patients complicated with PVST were divided into symptomatic group ( n=48) and asymptomatic group ( n=104). The differences in general information, laboratory test indicators, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), Balthazar computed tomography (CT) score, local and systemic complications were compared between symptomatic group and asymptomatic group. Two independent sample t test, two sample rank sum test, and chi-square test were used for statistical analysis. The binary logistic regression was used for multivariate analysis. Results:The severe acute pancreatitis (SAP) complicated with PVST was common, accounted for 73.0% (111/152), and the hospital mortality rate was 14.5% (22/152). The splenic vein (46.1%, 70/152) was the most common single vessel involved. The hospital stay of the symptomatic group was longer than that of the asymptomatic group, the hospitalization costs and hospital mortality of the symptomatic group were both higher than those of the asymptomatic group ((26.31±19.38) d vs. (15.11±9.31) d, (103 463.68±15 312.74) yuan vs. (37 199.38±4 647.17) yuan, 25.0%, 12/48 vs. 9.6%, 10/104, respectively), and the differences were statistically significant ( t=-3.809 and -4.141, χ2=6.280; all P<0.05). The lactic acid dehydrogenase, C-reactive protein, and prothrombin time of the symptomatic group were all higher than those of the asymptomatic group (4.78 μmol·s -1·L -1, 2.96 μmol·s -1·L -1 to 7.82 μmol·s -1·L -1 vs. 4.42 μmol·s -1·L -1, 3.29 μmol·s -1·L -1 to 9.30 μmol·s -1·L -1; 69.53 mg/L, 29.49 mg/L to 147.14 mg/L vs. 40.90 mg/L, 8.88 mg/L to 104.89 mg/L; (16.88±8.23) s vs. (14.12±1.59) s), however the hematocrit and blood calcium in the symptomatic group were both lower than those of the asymptomatic group ((34.97±8.96)% vs. (39.18±7.17)%, (2.01±0.32) mmol/L vs. (2.17±0.19) mmol/L), and the differences were all statistically significant ( Z=-2.067 and -1.977, t=-2.281, 3.072 and 3.083; all P<0.05). The scores of APACHE Ⅱand Balthazar CT, the rate of local complications of pancreatic necrosis, and systemic complications including abdominal hemorrhage, septic shock, acute respiratory distress syndrome, lung infection and pleural effusion of the symptomatic group were higher than those of the asymptomatic group (7.21±3.84 vs. 5.27±2.31, 7.10±1.57 vs. 4.83±1.87, 87.5%, 42/48 vs. 28.8%, 30/104; 10.4%, 5/48 vs. 1.9%, 2/104; 18.8%, 9/48 vs. 1.9%, 2/104; 25.0%, 12/48 vs. 3.8%, 4/104; 91.7%, 44/48 vs. 60.6%, 63/104; 85.4%, 41/48 vs. 49.0%, 51/104; respectively), and the differences were statistically significant ( t=-3.241 and -7.331, χ2=45.320, 5.393, 13.852, 15.604, 15.323 and 18.191; all P<0.05). The results of binary logistic regression showed that Balthazar CT score was an independent risk factor for symptomatic PVST ( P<0.01), and odds ratio (95% confidence interval) was 1.79 (1.41 to 2.29). Conclusions:Balthazar CT score is an influencing factor of symptomatic PVST in AP patients, and patients with high scores should be treated early to improve the prognosis.

The etiology and pathogenesis of autoimmune hepatitis (AIH) remain unclear and are currently considered to be associated with genetic susceptibility and environmental factors. Regulatory T (Treg) cells play an immunosuppressive role by secreting IL-10 and TGFβ, while T helper 17 (Th17) cells mainly promote inflammatory response, suggesting that Treg cells, Th17 cells, and the dynamic balance between them may be involved in the development and progression of AIH; however, further studies are needed to explore related participation mechanisms. This article reviews the association between Treg/Th17 cells and AIH in recent years and elaborates on their mechanism of action and therapeutic targets.

Objective:To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China.Methods:Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women′s socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis.Results:A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95% CI: 4.5%－6.1%) and 13.1% (95% CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions:In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

Objective:To observe the changes of microperimeter and OCT angiography (OCTA) in idiopathic macular hole (IMH) before and after operation, and to explore the correlation between the changes and visual acuity.Methods:From January 2018 to January 2019, 41 patients (41 eyes) with IMH who underwent pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) flap surgery in Tianjin Eye Hospital were included in this study. Among them, 8 patients (8 eyes) were male and 33 patients (33 eyes) were female. The average age was 64.02±6.46 years. The average course of disease was 7.00±8.85 months. BCVA, microperimeter and OCTA were performed. The retinal mean sensitivity (RMS) at 10 ° and fovea 2 ° fixation rate (P1) and binary contour ellipse area (63% BCEA) were measured by macular integrity assessment instrument. The central retinal thickness (CRT), choroidal blood flow area (CFA), superficial and deep retinal blood flow density (FAVD, FDVD), foveal avascular zone (FAZ) and blood flow densitywithin the width of FAZ 300 μm (FD-300) were measured by OCTA. Twenty one and 19 eyes with or without ILM flap operation were treated with 25G standard three incision PPV. The follow-up time was more than 6 months. Paired t-test was used to compare the indexes before and after operation. Pearson correlation analysis was performed for the correlation between logMAR visual acuity and microperimeter variables and OCTA variables. Nonparametric test was performed for paired comparison between affected eyes and contralateral eyes before and after operation.Results:At 6 months after operation, logMAR visual acuity ( t=-12.33), RMS ( t=7.94), P1 ( t=3.21), 63% BCEA ( t=-3.98), CRT ( t=-9.17), CFA ( t=8.14), FSVD ( t=3.75), FDVD ( t=3.88) were significantly improved compared with those before operation ( P<0.001). The difference of FAZ area ( t=-1.40) and FD-300 ( t=1.95) before and after operation were not statistically significant ( P>0.05). The results of correlation analysis showed that logMAR visual acuity 6 months after surgery was correlated with preoperative logMAR visual acuity, MIN, RMS, P1, 63% BCEA, FSVD, FDVD and FAZ ( r=0.432、0.527、-0.410、-0.383、0.349、-0.406、-0.373、0.407; P<0.05). At 6 months after operation, the indexes of the affected eyes were significantly improved compared with those before operation, but worse than those of the contralateral eyes ( P<0.05). Conclusions:PPV for IMH can effectively improve the visual acuity, retinal function and foveal microvascular circulation. Retinal function and blood circulation changes have a significant impact on postoperative visual acuity.

Objective To explore the CT and MRI imaging and clinicopathological features of extranodal NK/T cell lymphoma (NK/TCL). Methods Sixty-six patients with NK/TCL diagnosed from 2002 June to 2016 April in Beijing Tongren Hospital with intact CT and/or MRI imaging results were enrolled in this study. All the patients had tailed clinical information and follow-up. The imaging and clinicopathological features were analyzed retrospectively and their prognostic value on overall survival was analyzed. Results There were 49 males and 17 females with median age of 42 years. The median follow-up time was 18 months. The cases showed surrounding invasions including 10 cases (15.2 %) in soft palate, 5 cases (7.6 %) in hard palate, 2 cases(3.0 %) in tonsil, 8 cases(12.1 %) in upper lip, 13 cases(19.7 %) in maxillofacial soft tissue, 9 cases (13.6 %) in eyelid, 10 cases (15.2 %) in orbital, 3 cases (4.5 %) in maxilla, 6 cases (9.1 %) in pterygopalatine fossa,6 cases(9.1 %)in infratemporal fossa,3 cases(4.5 %)in skull base, 3 cases(4.5 %) in eyeball and 2 cases (3.0 %) in brain tissue. Kaplan-Meier survival analysis found that the 2-year overall survival rates of the patients with the involvement of hard palate, upper lip, maxillofacial soft tissue, eyelid, orbital, maxillary, eyeball and brain organizer were lower than those of the patients without the involvement of these sites(χ2values were 4.470,4.041,4.456,13.933,8.986,4.000,44.121,6.527,16.822,respectively, all P< 0.05). Further multivariate Cox regression analysis showed that maxilla and brain involvement were independent adverse factors (RR=34.717, 95 % CI 3.404-354.035, P=0.003; RR=37.545, 95 % CI 3.188-442.187, P= 0.004). Conclusions MRI and CT examinations are of great value in diagnosis and prognostic assessment of NK/TCL. Clinicians can make correct and timely diagnosis by comprehensive clinical, radiological and pathological features and can make a detailed clinical assessment to give patients appropriate treatment,thus improving the outcome of the NK/TCL patients.

Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation.Limited to the standards of tumor tissue samples and detection methods,still some people can't receive target therapy following genetic guidance.This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs.Methods We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation,who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital,analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs.Results The objective response rate (ORR)was 52.8％ and the disease control rate (DCR) was 89.3％.The results showed that,patients with high CEA level before treatment responded better to TKIs (ORR 61.3％ vs 35.9％,DCR 95.2％ vs 74.4％,P＜0.001).Similar phenomena was found in patients with CEA decreased 1 month later (61.5％ vs 25％,P=0.002).Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo,P=0.027).To the opposite,PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo,P=0.029;9.0 mo vs 11.5 mo,P=0.023,respectively).Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1,normal baseline CYFRA21-1 and CEA decline predicted longer PFS.The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo,P=0.003;22.7 mo vs 55.0 mo,P＜0.001,respectively),while independent of CEA.Conclusion High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma.While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.

Objective To detect the therapeutic effectiveness of electro-acupuncture combined with Leitoufenggranules for primary trigeminal neuralgia.MethodsA total of 60 patients with PTN were randomly divided into the control group and the treatment group (30 in each group). Control group received Carbamazepine, and the treatment group received the electro-acupuncture combined withLeitoufeng granules. Both groups were treated for 15 days as a period of treatment with 3 treatments in total. The outcomes were S hort form of the McGill Pain Questionnaire (SF-MPQ), painratingindex (PRI), the number of word feature (NWC), the present painindex (PPI), the Visual Analogue Scale (VAS) the clinical effect rate and recurrence rate. Results After treatment, compared with the control group, the effect rate (96.67%vs. 70.00%,χ2=5.880,) in the treatment group showed significantly higher (P=0.015). Compared with the control group, PRI (0.20 ± 0.47 vs. 3.33 ± 4.65,t=3.592), NWC (0.20 ± 0.48vs. 1.40 ± 1.87,t=3.345), VAS (0.20 ± 0.48vs. 1.27 ± 1.66, t=3.321), PPI (0.17 ± 0.38vs.0.90 ± 0.99,t=3.771) and the total score (0.79 ± 1.83vs. 6.90 ± 9.05,t=3.602) in the treatment group were significantly lower (P<0.01). In the follow-up of 3 months, compared with control group, the recurrence rate (10.0%vs.56.6%,χ2=12.675) in the treatment group significantly lower (P<0.01). Conclusion As to the treatment of primary trigeminal neuralgia, the effect of acupuncture combined with Leitoufeng granules was superior to the Carbamazepine.

OBJECTIVE: To determine the combined cytotoxic effect and the molecular basis of triptolide and sodium cantharidinate on hepatoma cell line 7721.
 METHODS: After treating the hepatoma cell line 7721 with triptolide(9, 18, or 36 μg/mL) and/or sodium cantharidinate (2, 5, or 10 μg/mL), cell viability assay and apoptosis were examined by MTT and flocytometry, respectively. The protein levels of caspase 3 and nuclear factor κB were analyzed by Western blot.
 RESULTS: Viability of hepatoma cell line 7721 was inhibited by either the therapy of triptolide and/or sodium cantharidinate (P<0.05) in a time- and dose-dependent manner. The combined effects of both drugs were better than those of the single drug (P<0.05). The combined therapy down-regulated the expression of NF-κB p65 (P<0.05) while up-regulated the expression of caspase-3 (P<0.05).
 CONCLUSION Triptolide and sodium cantharidinate exert a synergistic toxic effect on hepatoma cell line 7721, which is related to increasing capase-3 activity and suppression of NF- κB.
Apoptosis ; drug effects ; Cantharidin ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; Caspase 3 ; drug effects ; Cell Line, Tumor ; Diterpenes ; pharmacology ; therapeutic use ; Down-Regulation ; Drug Therapy, Combination ; Epoxy Compounds ; pharmacology ; therapeutic use ; Humans ; Liver Neoplasms ; drug therapy ; NF-kappa B ; drug effects ; Phenanthrenes ; pharmacology ; therapeutic use ; Transcription Factor RelA