Surgery, chemoradiotherapy, or chemoradiation plus immunotherapy: Treatment strategies for nonmetastatic anal squamous cell carcinoma.

The current standard of care for anal squamous cell carcinoma (ASCC) is definitive concurrent chemoradiotherapy (CRT). However, about a third of patients may experience treatment failure. Recently, immunotherapy has emerged as a novel strategy for metastatic ASCC patients. We evaluated the efficacy and safety of surgery, CRT alone, and CRT with immunotherapy (CRT-I) in 100 nonmetastatic ASCC patients, treated from April 2012 through May 2023, by determining survival outcomes and acute adverse events. The median (range) follow-up was 30.7 (7.6 to 134.9) months. The study cohort 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were 80.7 %, 62.2 %, 71.1 %, and 67.6 %, respectively. The Surgery group had significantly lower rates than the CRT and CRT-I groups for 3-year PFS (33.1% vs. 65.2% vs. 92.9 %, P < 0.001), DMFS (46.7% vs. 74.6% vs. 92.9 %, P = 0.002) and LRFS (37.0% vs. 73.3% vs. 92.9 %, P < 0.001), respectively. All patients receiving CRT-I were alive at last follow-up. Of 100 patients, 26 (26.0 %) experienced severe (≥ grade 3) acute toxicity. Of 24 patients receiving CRT-I, 8 (33.3 %) had severe acute toxicity. Using immunohistochemistry, peritumoural stromal infiltration by CD8+ T cells was significantly higher after CRT-I compared to before CRT-I and to after CRT alone. The addition of immunotherapy to CRT may be an effective first-line treatment option with favourable survival outcomes and acceptable toxicity for patients with ASCC. A prospective, randomized trial assessing the efficacy of CRT combined with a PD-1 inhibitor in patients with locally advanced ASCC is in progress.

[Discussing the basic ecological relations of sand dune vegetation process]. / è®ºæ²™ä¸˜æ¤è¢«è¿‡ç¨‹çš„åŸºæœ¬ç”Ÿæ€å ³ç³».

Dune is often considered as a degraded ecosystem. Natural vegetation restoration and stable artificial vegetation construction are the basic means restoring dune ecosystem. Based on long-term study of dune ecosystem, by taking into consideration both the philosophical principles of unity of opposites and dynamic change, and related ecological theories, we put forward some ecological relations that should be paid attention to in the study of vegetation assembly from the perspective of the uniqueness of dune ecosystem. We discussed the necessity of coupling relationships of scale-pattern-process and the transformation of synergy-tradeoff relationships, interpreted the importance of distinguishing sand dune stabilized and shifting phases, disturbance and stress, wind erosion and sand burial in the study of vegetation process. We further explored the applied value of niche law or neutral law in the study of dune vegetation process. Finally, we discussed the issues that should be paid attention to in the study of dune vegetation process from the aspects of adaptability to aeolian activities and drought tolerance, physiological and reproductive process, sexual and asexual reproduction of plants. This study would provide theoretical supports for vegetation restoration and stable vegetation construction of dune ecosystem.

[Shelterbelt construction in the scenario of coordinated development of mountain, river, forest, farmland, lake, grassland, and sandy land ecosystems in semi-arid wind-sand areas: Principles and methods]. / 半干旱风沙区"山水林田湖草沙"建设中防护林营建的原理与方法.

We established the systematic concept framework of shelterbelt construction, with "shelterbelts" as the core concern in the construction of integrated ecosystems including mountain, river, forest, farmland, lake, grassland and sandy-land in semi-arid wind-sand areas. In the construction of shelterbelts, it is necessary to adhere to the principles of scientific coordination and systematic management, considering the carrying capacity of water resources, the demand for dust control, the greening and beautification effects, as well as the principle of improving economic benefits. In practice, the construction methods should base on the types and temporal-spatial distribution of shelterbelts, following the shelterbelts construction theory and technology to form different structure and service functions, achieving the functional goals of shelterbelts. By focusing on the key elements including people, forests, grass, fields, water, and sand, we put forward the timeliness, practicality, and scientificity of shelterbelt construction, proposing construction methods for farmland shelterbelts, pastureland shelterbelts, windbreak and sand-fixing forests and protective forest around village (city), which might provide production technical support for the high-quality construction of green ecological barrier in northern China.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

Endoscopic retrograde cholangiopancreatography for diagnosing and treating pediatric biliary and pancreatic diseases.

BACKGROUND: This study evaluated the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients with biliary and pancreatic diseases. A retrospective analysis was conducted on 57 ERCP procedures performed in 41 children, primarily for treating pancreatic diseases. The overall success rate was 91.2%, with no major complications observed. Post-ERCP pancreatitis (PEP) occurred in 8.8% of cases. Follow-up examinations over one year showed no recurrence of biliary or pancreatic diseases. Notably, endoscopic treatment led to a significant increase in body mass index (BMI). These findings demonstrate the valuable role of ERCP in managing such conditions. AIM: To evaluate the safety and efficacy of ERCP for the management of biliary and pancreatic diseases in pediatric patients. METHODS: We conducted a retrospective analysis of data from children aged 1-18 years who underwent ERCP for biliary and pancreatic diseases at Beijing Children's Hospital between January 2021 and December 2022. The collected data included procedure time, endoscopic treatment, success rate, and postoperative complications. RESULTS: Forty-one children underwent 57 ERCP procedures, including 14 with biliary duct disease and 27 with pancreatic disease. The mean age of the patients was 7.48 ± 3.48 years. Biliary duct-related treatments were performed 18 times, and pancreatic disease treatments were performed 39 times. ERCP was primarily used to treat pediatric pancreatic diseases [68.4% (39/57) of the procedures]. The overall success rate was 91.2% (52/57 patients). PEP was noted in five patients (8.8%, 5/57), and no instances of bleeding, perforation, or cholangitis were observed. The patients were followed up for over one year, and no recurrence of biliary or pancreatic diseases was detected. Importantly, BMI significantly increased after endoscopic treatment compared to that before treatment (P = 0.001). CONCLUSION: The high success rate and lack of major complications support the valuable role of ERCP in the management of pediatric biliary and pancreatic diseases in the pediatric population.

Predictors of post-stroke depression: the perspective from the social convoy model.

BACKGROUND: Post-stroke depression (PSD) as one of the most common neuropsychiatric disorders after a stroke and is caused by many factors. However, the relationships among different factors and their potential contributions to PSD remain unclear. METHODS: Two hundred and seventy-six patients were recruited into this study. The general information questionnaire, the Patient Health Questionnaire-9, the Perceived Social Support Scale, the Family Assessment Device, the General Well-Being Scale, the Barthel Index, and the modified Rankin Scale were used to assess the condition of patients. Subsequently, we identify the main causes associated with the PSD and then performed a path analysis to clarify the direct, indirect and total effects among the variables. RESULTS: We found that age, stroke with coronary heart disease, neurological function, family function, social support, and general well-being had a significant impact on PSD (P < 0.05). Of these, neurological function had the largest total effect on PSD (ß = 0.451), social support contributed the most as a direct effect (ß = -0.306), and family function showed the largest indirect effect (ß = -0.264). CONCLUSION: Individual, disease, and social-psychological factors all contributed to the development of PSD. We should pay more attention to comprehensive assessment, especially for those with poor neurological function, and lacking family or social support. In addition, it would be preferable to provide them with necessary support and care strategies to reduce the incidence of PSD.

Phase I study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer.

BACKGROUNDAdoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has achieved remarkable clinical efficacy in metastatic cancers such as melanoma and cervical cancer (CC). Here, we explored the safety, feasibility, and preliminary tumor response and performed translational investigations of adjuvant immunotherapy using infusion of autogenous TILs (auto-TILs) following concurrent chemoradiotherapy (CCRT) in patients with CC who had locally advanced disease.METHODSTwenty-seven patients with CC with stage III-IV disease were recruited in this single-center, phase I study. TILs were isolated from lesions in the uterine cervix and generated under good manufacturing practice (GMP) conditions and then infused after CCRT plus i.m. IL-2 injections.RESULTSTILs from 20 of the 27 patients were successfully expanded, with a feasibility of 74.1%. Twelve patients received TILs following CCRT. Adverse events (AEs) were primarily attributable to CCRT. Only 1 (8.3%) patient experienced severe toxicity with a grade 3 hypersensitivity reaction after TIL infusion. No autoimmune AEs, such as pneumonitis, hepatitis, or myocarditis, occurred, and there were no treatment-related mortalities. Nine of 12 patients (75.0%) attained a complete response, with a disease control duration of 9-22 months. Translational investigation showed that the transcriptomic characteristics of the infused TIL products and some immune biomarkers in the tumor microenvironment and serum of patients with CC at baseline were correlated with the clinical response.CONCLUSIONTIL-based ACT following CCRT was safe in an academic center setting, with potentially effective responses in patients with locally advanced CC. "Hot" inflammatory immune environments were beneficial to the clinical efficacy of TIL-based ACT as adjuvant therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT04443296.FUNDINGNational Key R&D Program; Sci-Tech Key Program of the Guangzhou City Science Foundation; the Guangdong Province Sci-Tech International Key Program; the National Natural Science Foundation of China.

Association of time-varying changes in physical activity with cardiac death and all-cause mortality after ICD or CRT-D implantation.

OBJECTIVE: To evaluate the association of longitudinal changes in physical activity (PA) with long-term outcomes after implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) implantation. METHODS: Patients with ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed. Accelerometer-derived PA changes over 12 months post implantation were obtained from the archived home monitoring data. The primary endpoints were cardiac death and all-cause mortality. The secondary endpoints were the first ventricular arrthymia (VA) and first appropriate ICD shock. RESULTS: In 705 patients, 446 (63.3%) patients showed improved PA over 12 months after implantation. During a mean 61.5-month follow-up duration, 99 cardiac deaths (14.0%) and 153 all-cause deaths (21.7%) occurred. Compared to reduced/unchanged PA, improved PA over 12 months could result in significantly reduced risks of cardiac death (improved PA ≤ 30 min: hazard ratio (HR) = 0.494, 95% CI: 0.288-0.848; > 30 min: HR = 0.390, 95% CI: 0.235-0.648) and all-cause mortality (improved PA ≤ 30 min: HR = 0.467, 95%CI: 0.299-0.728; > 30 min: HR = 0.451, 95% CI: 0.304-0.669). No differences in the VAs or ICD shocks were observed across different groups of PA changes. PA changes can predict the risks of cardiac death only in the low baseline PA group, but improved PA was associated with 56.7%, 57.4%, and 62.3% reduced risks of all-cause mortality in the low, moderate, and high baseline PA groups, respectively, than reduced/unchanged PA. CONCLUSIONS: Improved PA could protect aganist cardiac death and all-cause mortality, probably reflecting better clinical efficacy after ICD/CRT-D implantation. Low-intensity exercise training might be encouraged among patients with different baseline PA levels.

A strategy of vascular-targeted therapy for liver fibrosis.

BACKGROUND AND AIMS: No effective treatments are available for liver fibrosis. Angiogenesis is deeply involved in liver fibrogenesis. However, current controversial results suggest it is difficult to treat liver fibrosis through vascular targeting. There are three different microvessels in liver: portal vessels, liver sinusoids, and central vessels. The changes and roles for each of the three different vessels during liver fibrogenesis are unclear. We propose that they play different roles during liver fibrogenesis, and a single vascular endothelial cell (EC) regulator is not enough to fully regulate these three vessels to treat liver fibrosis. Therefore, a combined regulation of multiple different EC regulatory signaling pathway may provide new strategies for the liver fibrosis therapy. Herein, we present a proof-of-concept strategy by combining the regulation of leukocyte cell-derived chemotaxin 2 (LECT2)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 signaling with that of vascular endothelial growth factor (VEGF)/recombinant VEGF (rVEGF) signaling. APPROACH AND RESULTS: The CCl4 -induced mouse liver fibrosis model and NASH model were both used. During fibrogenesis, vascular changes occurred at very early stage, and different liver vessels showed different changes and played different roles: decreased portal vessels, increased sinusoid capillarization and the increased central vessels the increase of portal vessels alleviates liver fibrosis, the increase of central vessels aggravates liver fibrosis, and the increase of sinusoid capillarization aggravates liver fibrosis. The combinational treatment of adeno-associated viral vector serotype 9 (AAV9)-LECT2-short hairpin RNA (shRNA) and rVEGF showed improved therapeutic effects, but it led to serious side effects. The combination of AAV9-LECT2-shRNA and bevacizumab showed both improved therapeutic effects and decreased side effects. CONCLUSIONS: Liver vascular changes occurred at very early stage of fibrogenesis. Different vessels play different roles in liver fibrosis. The combinational treatment of AAV9-LECT2-shRNA and bevacizumab could significantly improve the therapeutic effects on liver fibrosis.

[Principles and implementation of the integrated management of "mountain-river-forest-farmland-lake-grassland-sandland" in Horqin Sand Land, China]. / 科尔沁沙地"山水林田湖草沙"一体化治理原理及实施重点.

Integrated management of "mountain-river-forest-farmland-lake-grassland-sandland" has become an important concept of ecological environment construction in arid areas. Although some major projects have been implemented in the sand areas, but the scientific and technical principles of integrated management are not clear and have not been fully reflected in these projects. Considering such cases, we discussed the challenges, scientific principles, technical principles and implementation priorities of the integrated management of Horqin Sand Land. In Horqin Sand Land, the relationships between forest and farmland, forest and forest, forest and water, farmland and water, forest and grassland, sand land and water, farmland and grassland were not well coordinated, resulting in resource imbalance and low ecologic services. The integrated management should follow scientific principles and laws, including aeolian sand movement law, grassland interface theory, water resource balance theory, biodiversity maintenance theory, landscape ecology theory, and ecosystem services. At the technical level, the principles of water-sediment relationship coordination, landscape design optimization, prevention and control technologies and modes multi-directional synergia, natural and man-made landscapes harmonies, "production-ecological" space layout balance should be highlighted. The key points of integrated management should focus on the function improvement of sand dunes and shelter forests, the efficiency improvement of farmlands and grasslands, the ecological conservation of lakes, the greening and beautification of human settlements, the ecological restoration of engineering projects. This review could provide reference for the integrated ecological environment construction in Horqin Sand Land and the sand areas of northern China.

Treatment of patients with Covid-19 with a high dose of ulinastatin.

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.

Test and Numerical Model of Curved Steel-Concrete Composite Box Beams under Positive Moments.

Compared with straight steel-concrete composite beams, curved composite beams exhibit more complicated mechanical behaviors under combined bending and torsion coupling. There are much fewer experimental studies on curved composite beams than those of straight composite beams. This study aimed to investigate the combined bending and torsion behavior of curved composite beams. This paper presents static loading tests of the full elastoplastic process of three curved composite box beams with various central angles and shear connection degrees. The test results showed that the specimens exhibited notable bending and torsion coupling force characteristics under static loading. The curvature and interface shear connection degree significantly affected the force behavior of the curved composite box beams. The specimens with weak shear connection degrees showed obvious interfacial longitudinal slip and transverse slip. Constraint distortion and torsion behavior caused the strain of the inner side of the structure to be higher than the strain of the outer side. The strain of the steel beam webs was approximately linear. In addition, fine finite element models of three curved composite box beams were established. The correctness and applicability of the finite element models were verified by comparing the test results and numerical calculation results for the load-displacement curve, load-rotational angle curve, load-interface slip curve, and cross-sectional strain distribution. Finite element modeling can be used as a reliable numerical tool for the large-scale parameter analysis of the elastic-plastic mechanical behavior of curved composite box beams.

Minor allele of rs55763075 located in MTHFR is associated with the risk of cognitive impairment after anesthesia via modulating miR-34b.

This study aimed to investigate the association between cognitive impairment after general anesthesia and rs55763075 polymorphisms. We enrolled and grouped patients undergoing general anesthesia according to their genotypes of rs55763075 polymorphism. Mini-Mental State Examination (MMSE) scoring was performed to evaluate the cognitive status of patients. Quantitative real-time PCR was carried out to analyze the expression of methylenetetrahydrofolate reductase (MTHFR) mRNA and miR-34b while Western blot was performed to evaluate the expression of MTHFR protein. Furthermore, we studied the effect of rs55763075 polymorphism on the expression of MEHFR via luciferase assay. Accordingly, we found that the MMSE score in GG/GA groups was significantly higher than that in AA group. And a significant reduction of MTHFR mRNA expression was observed in the serum and peripheral blood mononuclear cells (PBMCs) of patients carrying AA genotype compared with the patients carrying GG/GA genotypes. Moreover, the MTHFR expression was much lower in the cultured AA-genotyped cells transfected with miR-34b. Luciferase assay results also showed that miR-34b transfection reduced luciferase activity in the cells carrying A allele but not in cells carrying G allele. In summary, the data of this study showed that minor allele (A) of rs55763075 polymorphisms in the 3'-untranslated region of MTHFR mRNA generated a potential binding site for miR-34b, which led to reduced level of folic acid in the patients carrying the AA genotype. Furthermore, we found that the MMSE score of AA-genotyped patients was lower than that of patients carrying GG/GA genotypes.

Stapled transperineal repair for low- and mid-level rectovaginal fistulas: A 5-year experience and comparison with sutured repair.

BACKGROUND: Currently, rectovaginal fistula (RVF) continues to be a surgical challenge worldwide, with a relatively low healing rate. Unclosed intermittent suture and poor suture materials may be the main reasons for this. AIM: To evaluate the efficacy and safety of stapled transperineal repair in treating RVF. METHODS: This was a retrospective cohort study conducted in the Coloproctology Department of The Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). Adult patients presenting with RVF who were surgically managed by perineal repair between May 2015 and May 2020 were included. Among the 82 total patients, 37 underwent repair with direct suturing and 45 underwent repair with stapling. Patient demographic data, Wexner faecal incontinence score, and operative data were analyzed. Recurrence rate and associated risk factors were assessed. RESULTS: The direct suture and stapled repair groups showed similar clinical characteristics for aetiology, surgical history, fistula features, and perioperative Wexner score. The stapled repair group did not show superior results over the suture repair group in regard to operative time, blood loss, and hospital stay. However, the stapled repair group showed better postoperative Wexner score (1.04 ± 1.89 vs 2.73 ± 3.75, P = 0.021), less intercourse pain (1/45 vs 17/37, P = 0.045), and lower recurrence rate (6/45 vs 17/37, P = 0.001). There was no protective effect from previous repair history, smaller diameter of fistula (< 0.5 cm), better control of defecation (Wexner < 10), or stapled repair. Direct suture repair and preoperative high Wexner score (> 10) were risk factors for fistula recurrence. Furthermore, stapled repair gave better efficacy in treating complex RVFs (i.e., multiple transperineal repair history, mid-level fistula position, and poor control of defecation). CONCLUSION: Stapled transperineal repair is advantageous for management of RVF, providing a high primary healing rate and low recurrence rate.

Methylation of ERß 5'-untranslated region attenuates its inhibitory effect on ERα gene transcription and promotes the initiation and progression of papillary thyroid cancer.

Normal thyroid tissue displays a prevalent expression of ERß than ERα, which drastically turns upside down in the initiation and progression of papillary thyroid cancer (PTC). The underlying molecular mechanism of this phenomenon remains unclear. Here, we demonstrated that ERα and ERß were coexpressed in human thyroid tissues and cells. ERα mRNA (A-1) and ERß mRNA (0N-1), transcribed from Promoter A of ERα gene and Promoter 0N of ERß gene, respectively, were the major mRNA isoforms which mainly contributed to total ERα mRNA and total ERß mRNA in human thyroid-derived cell lines and tissues. The expression levels of ERα mRNA (A-1) and total ERα mRNA were gradually increased, and those of ERß mRNA (0N-1) and total ERß mRNA were decreased by degree in the initiation and progression of PTC. No aberrant DNA methylation of ERα 5'-untranslated region was involved in its up-regulation; however, aberrant DNA methylation in Promoter 0N and Exon 0N of ERß gene was found to be involved in its down-regulation in the initiation and progression of PTC. ERß can repress ERα gene transcription via recruitment of NCoR and displacement of RNA polymerase II at the Sp1 site in ERα Promoter A-specific region in thyroid-derived cells. It is suggested that DNA methylation of CpG islands in Promoter 0N and Exon 0N of ERß gene leads to a decreased ERß gene expression, which attenuates its inhibitory effect on ERα gene transcription and results in an increased ERα gene expression, cell proliferation, initiation, and progression of PTC.

Proposal for modified inguinofemoral lymphadenectomy derived from investigation of anatomic distribution of sentinel and metastatic nodes in vulvar cancer.

OBJECTIVE: We aimed to develop a less invasive inguinofemoral lymphadenectomy (IFL) approach for vulvar cancer based on the investigation of the anatomic distribution of sentinel and metastatic nodes. METHODS: Patients with vulvar cancer treated by surgery between 1995 and 2019 were retrospectively reviewed. A seven-field method was adopted to assign the anatomic locations for lymph nodes removed via IFL or sentinel node biopsy. Only patients with nodal metastasis or sentinel nodes were included. RESULTS: A total of 102 patients with eligible data were analyzed. Nodal metastasis was confirmed in 118 groins undergoing IFL; sentinel node detection succeeded in 46 groins. The medial-inguinal field had the highest rate of nodal metastasis involvement (59.3%, 70/118) and sentinel nodes present (73.9%, 34/46). The inferior-femoral field was involved only in one groin with quadruple-field metastases. The lateral-inguinal field was not involved in any groin. Neither the lateral-inguinal nor the inferior-femoral field presented sentinel nodes. CONCLUSION: The lateral-inguinal and inferior-femoral fields of the groins have a low risk of developing nodal metastasis. Therefore, a modified IFL preserving these fields can be established to reduce surgical morbidity without sacrificing its therapeutic effect.

Plasma big endothelin-1 is an effective predictor for ventricular arrythmias and end-stage events in primary prevention implantable cardioverter- defibrillator indication patients.

OBJECTIVE: To investigate whether plasma big endothelin-1 (ET-1) predicts ventricular arrythmias (VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator (ICD) indication patigents. METHODS: In total, 207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analyzed. The cohort was divided into three groups according to baseline plasma big ET-1 tertiles: tertile 1 (< 0.38 pmol/L, n = 68), tertile 2 (0.38-0.7 pmol/L, n = 69), and tertile 3 (> 0.7 pmol/L, n = 70). The primary endpoints were VAs. The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation. RESULTS: During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (r = 0.165, P = 0.018), serum creatinine concentration (Scr; r = 0.147, P = 0.034), high-sensitivity C-reactive protein (hs-CRP; r = 0.217, P = 0.002), Lg NT-pro BNP (r = 0.463, P < 0.001), left ventricular end diastolic diameter (LVEDD; r = 0.234, P = 0.039) and negatively correlated with left ventricular ejection fraction (LVEF; r = -0.181, P = 0.032). Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events (P < 0.05). In multivariate Cox regression models, big ET-1 was an independent risk factor for VAs (hazard ratio (HR) = 3.477, 95% confidence interval (CI): 1.352-8.940, P = 0.010, tertile 2 vs. tertile 1; HR = 4.112, 95% CI: 1.604-10.540, P = 0.003, tertile 3 vs. tertile 1) and end-stage events (HR = 2.804, 95% CI: 1.354-5.806, P = 0.005, tertile 2 vs. tertile 1; HR = 4.652, 95% CI: 2.288-9.459, P < 0.001, tertile 3 vs. tertile 1). CONCLUSIONS: In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.

Epidemics of HIV Infection among Heavy Drug Users of Depressants Only, Stimulants Only, and Both Depressants and Stimulants in Mainland China: A Series, Cross-Sectional Studies.

Background: Heavy drug users was a global consensus high-risk population of HIV infection. However, the specific impact of drug on HIV infection has not yet been established. Depressants and stimulants were most widely used drugs in mainland China, and mix use of the two drugs was also serious. We assessed the HIV infection rate and trends in heavy drug users by analyzing data from the National Dynamic Management and Control Database for Drug Users (NDMCDDU). Methods: All heavy drug users with HIV test results in NDMCDDU from 2008 to 2016 were grouped into depressants only group (DOG), stimulants only group (SOG), and both depressants and stimulants group (DSG). We used joinpoint regression to examine trends of HIV infection rates. Multivariable logistic regression was used to examine factors related to HIV infection. Results: A total of 466,033 heavy drug users with 9522 cases of HIV infection were included in this analysis. HIV infection rate was estimated at 2.97% (95% CI 2.91-3.04%) of 265,774 users in DOG, 0.45% (95% CI 0.42-0.49%) of 140,895 users in SOG, and 1.65% (95% CI 1.55-1.76%) of 59,364 users in DSG. In DOG, a U-shaped curve of HIV infection rate decreased from 3.85% in 2008 to 2.19% in 2010 (annual percent change (APC) -12.9, 95% CI -19.3--6.0, p < 0.05), then increased to 4.64% in 2016 (APC 8.3, 95% CI 6.1-10.4, p < 0.05) was observed. However, SOG and DSG showed consistent increases from 0.15% in 2008 to 0.54% in 2016 (APC 8.2, 95% CI 4.8-11.8, p < 0.05) and from 0.78% in 2008 to 2.72% in 2016 (APC 13.5, 95% CI 10.7-16.4, p < 0.05), respectively. HIV infection rate of DOG in the southwest region presented a U-shaped trend. All groups showed significant increases in HIV infection in east and central regions. Conclusions: The U-shaped curve for HIV infection rate among DOG users and consistent increases among SOG and DSG users implies drug abuse is still a critical focus of HIV infection in China. It is urgently needed to reassess the effectiveness of current strategies on HIV prevention and control among drug users.

[Effects of UHRF1 on Estrogen Receptor and Proliferation, Invasion and Migration of BCPAP Cells in Thyroid Papillary Carcinoma].

OBJECTIVE: To investigate the effects of ubiquitin-like PDH and ring finger domain 1 (UHRF1) on the expression ratio of estrogen receptor (ER) α/ERß, and to explore the experimental mechanism of UHRF1 affecting the proliferation, invasion and migration of BCPAP cells in papillary thyroid carcinoma. METHODS: The protein and mRNA expressions of UHRF1, ERα and ERß in normal thyroid Nthy-ori3-1 cells and thyroid papillary carcinoma BCPAP cells were detected by Western blot and qRT-PCR. BCPAP cells were treated with Scrambled siRNA and UHRF1 siRNA, respectively. The expressions of ER α and ER ß mRNAs were detected by qRT-PCR. MTT and Transwell were used to determine the proliferation, invasion and migration in each group of BCPAP cells. RESULTS: Compared with Nthy-ori3-1 cells, the expressions of UHRF1 and ERα proteins and mRNAs in BCPAP cells were significantly up-regulated ( P<0.05), while the expressions of ERß protein and mRNA were significantly down-regulated ( P<0.05). Compared with the control group and Scrambled siRNA group, the expression of ER α mRNA in BCPAP cells transfected with UHRF1 siRNA was significantly decreased ( P<0.05), while the expression of ER ß mRNA was significantly increased ( P<0.05). The proliferation, invasion and migration of BCPAP cells transfected with UHRF1 siRNA were significantly decreased ( P<0.05). CONCLUSION: UHRF1 upregulates ERα/ERß expression ratio and promotes proliferation, invasion and migration of BCPAP cells in papillary thyroid carcinoma.