Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective:To investigate the clinical effects of stereotactic-guided endoscopic hematoma removal combined with early systematic rehabilitation training on hypertensive intracerebral hemorrhage in the basal ganglia.Methods:A total of 130 patients with hypertensive intracerebral hemorrhage in the basal nucleus who received treatment in Zhejiang Veteran Hospital from June 2019 to December 2021 were included in this randomized control study. They were randomly divided into a control group and a study group ( n = 65 per group). The control group received minimally invasive hematoma puncture. The study group received stereotactic-guided neuroendoscopic hematoma removal. After surgery, early systematic rehabilitation training was carried out, and surgical indicators were recorded. The levels of serum inflammatory factors and stress factors were determined. The recurrence, death, and complications as well as prognosis of cerebral hemorrhage were recorded in each group. Results:The operative time in the study group was (85.39 ± 5.24) minutes, which was significantly longer than (64.17 ± 4.31) minutes in the control group ( t = -14.56, P < 0.001). Hematoma clearance rate in the study group was (94.66 ± 5.18) %, which was significantly higher than (76.82 ± 5.39) % in the control group ( t = -17.63, P < 0.001). At 24 hours after surgery, tumor necrosis factor-α, interleukin-1, norepinephrine, and hydrocortisone levels in the study group were (68.29 ± 5.36) ng/L, (237.62 ± 13.87) ng/L, (75.39 ± 5.82) μg/L, and (30.96 ± 2.97) μg/L, respectively, which were significantly lower than (74.61 ± 5.62) ng/L, (295.47 ± 14.69) ng/L, (91.62 ± 6.41) μg/L, and (38.25 ± 3.16) μg/L in the control group ( t = 7.95, 18.42, 16.84, 11.75, all P < 0.001). There was no significant difference in the 6-month mortality rate between the two groups ( P > 0.05). The recurrence rate of cerebral hemorrhage and the overall incidence of complications in the study group were (1.54% (1/65) and (10.77% (7/65) in the study group, respectively, which were significantly lower than 12.31% (8/65) and 27.69% (18/65) in the control group ( χ2 = 4.30, 5.99, both P < 0.05). The overall excellent and good prognosis rate within 6 months in the study group was 86.15% (56/65), which was significantly higher than 67.69% (44/65) in the control group ( χ2 = 6.24, P < 0.05). Conclusion:Compared with minimally invasive hematoma puncture and drainage surgery, stereotactic-guided neuroendoscopic hematoma removal takes longer time, but it can better effectively increase hematoma removal rate and alleviate stress and inflammatory reactions in patients with hypertensive intracerebral hemorrhage in the basal ganglia. Early systematic rehabilitation training combined with stereotactic guided neuroendoscopic hematoma removal can help reduce the risk of recurrence and complications of cerebral hemorrhage and improve prognosis.

BACKGROUND: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are the main causes of restenosis (RS) in diabetic lower extremity arterial disease (LEAD). However, the relevant pathogenic mechanisms are poorly understood. METHODS: In this study, we introduced a "two-step injury protocol" rat RS model, which started with the induction of atherosclerosis (AS) and was followed by percutaneous transluminal angioplasty (PTA). Hematoxylin-eosin (HE) staining and immunohistochemistry staining were used to verify the form of RS. Two-step transfection was performed, with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g, to explore the possible mechanism by which Lin28a exerted effects. 5-ethynyl-2΄-deoxyuridine (EdU) and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of Lin28a protein and let-7 family members. RESULTS: Using a combination of in vitro and in vivo experiments, we discovered that let-7c, let-7g, and microRNA98 (miR98) were downstream targets of Lin28a. More importantly, decreased expression of let-7c/let-7g increased Lin28a, leading to further inhibition of let-7c/let-7g. We also found an increased level of let-7d in the RS pathological condition, suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs. CONCLUSION These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g, which may be responsible for the vicious behavior of VSMCs in RS.
Rats ; Animals ; Down-Regulation ; MicroRNAs/metabolism* ; Feedback ; Cell Proliferation/genetics* ; Atherosclerosis

Anti neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a systemic disease characterized by small vessel wall inflammation and cellulose necrosis mediated by ANCA. Renal injury caused by AAV is called ANCA-associated glomerulonephritis (AAGN). The paper reported a case of AAV with renal damage combined with human immunodeficiency virus (HIV) infection. The patient was an elderly male with clinical manifestations of hematuria and uremia. Renal pathological examination showed AAV and renal injury. This case is the first report in China while reviewing the relevant literature, and it is still inconclusive whether this is an overlap of the two diseases or a specific pathological type of HIV-associated nephritis. We believe that AAV has the potential to occur in HIV-infected patients, so clinicians should not ignore the phenomenon of ANCA positivity in HIV-infected patients, and the follow-up of such patients needs to be enhanced. Clinical and renal pathological examinations are the main methods to diagnose HIV infection with AAV. At the same time, there are no clear guideline guidelines on how to administer immunosuppressive therapy for such patients who have immunodeficiency and are at higher risk of opportunistic infections, and in whom to make the best possible outcomes.

In the face of a serious occupational disease prevention and control situation, the lack of efficient supervision and regulation methods has become a prominent contradiction. This paper reviewed the progress and application of occupational health grading and classification supervision methods for employers in China in recent years, and analyzed the characteristics and limitations of selected methods. The grading and classification supervision methods have gradually developed from considering only inherent health risk of occupational disease hazards, to considering both inherent attributes of occupational disease hazards and exposure duration. Some regional authorities introduced trial measures for grading and classification of occupational health supervision by embracing exposure level of an occupational disease hazard of interest, associated outcome severity, and occupational health management situation of targeted employers. In October 2022, the National Disease Control and Prevention Bureau issued the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which further promoted the establishment of a differentiated occupational health supervision model. Grading and classification of occupational health supervision can improve the supervision efficiency of public health administration departments and promote employers to fulfill the main responsibility of occupational disease prevention and control.

Background: The Lymphadenectomy in Ovarian Neoplasms (LION) study revealed that systemic lymphadenectomy did not bring survival benefit for advanced ovarian cancer patients with clinically normal lymph nodes and was associated with a higher incidence of operative complications. However, there is no consensus on whether lymphadenectomy has survival benefit or not in early epithelial ovarian cancer (EOC). Methods We designed the LOVE study, a multicenter, randomized controlled, phase III trial to compare the efficacy and safety of comprehensive staging surgery with or without lymphadenectomy in stages IA-IIB EOC and fallopian tube carcinomas (FTC). The hypothesis is that the oncological outcomes provided by comprehensive staging surgery without lymphadenectomy are non-inferior to those of conventional completion staging surgery in early-stage EOC and FTC patients who have indications for post-operative adjuvant chemotherapy. Patients assigned to experimental group will undergo comprehensive staging surgery, but lymphadenectomy. Patients assigned to comparative group will undergo completion staging surgery including systematic pelvic and para-aortic lymphadenectomy. All subjects will receive 3–6 cycles of standard adjuvant chemotherapy. Major inclusion criteria are pathologic confirmed stage IA-IIB EOC or FTC, and patients have indications for adjuvant chemotherapy either confirmed by intraoperative fast frozen section or previous pathology after an incomplete staging surgery. Major exclusion criteria are non-epithelial tumors and low-grade serous carcinoma. Patients with severe rectum involvement which lead to partial rectum resection will be excluded. The sample size is 656 subjects. Primary endpoint is disease-free survival.

Background: Cervical cancer is still present a major public health problem, especially in developing countries. In International Federation of Gynaecology and Obstetrics 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopical positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. However, there are no prospective study reporting that resecting macroscopic nodes before concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer and no guidelines for surgical resection of bulky lymph nodes. The CQGOG0103 study is a prospective, multicenter and randomized controlled trial (RCT) evaluating lymph node dissection on stage IIICr of cervical cancer. Methods Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by computed tomography [CT]/magnetic resonance imaging/positron emission tomography/CT) and the short diameter of image-positive lymph node ≥15 mm. 452 patients will be equally randomized to receive either CCRT (pelvic external-beam radiotherapy [EBRT]/extended-field EBRT + cisplatin [40 mg/m2] or carboplatin [the area under curve=2] every week for 5 cycles + brachytherapy) or open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. A total of 452 patients will be enrolled from multiple hospitals in China within 4 years and followed up for 5 years.

Objective:To explore changes in high-risk sexual behaviors and associated factors in HIV-infected men who have sex with men (MSM) in industrial workers, and provide evidence for designing behavioral interventions for this population.Methods:In this observational study, HIV-infected MSM were recruited in industrial workers using convenient sampling during August to September 2021. The sample size was estimated to be 530. A questionnaire was used and combined with routine follow-up to collect socio-demographic characteristics, high-risk sexual behaviors, partner notification, viral load testing and history of sexually transmitted diseases before and after diagnosis of HIV infection. The χ2 test was used to analyze the changes in high-risk sexual behaviors before and after diagnosis and logistic regression was conducted to identify factors associated with high-risk sexual behaviors. Results:A total of 560 HIV-infected MSM in industrial workers were recruited in this study. Of whom, 32.1% (180/560) had unprotected anal intercourse (UAI) within 12 months after diagnosis . The proportions of those having UAI with casual, commercial and regular same-sex partners significantly decreased from 73.4% (381/519), 75.1% (187/249) and 69.5% (207/298) within 12 months before diagnosis to 36.2% (146/403), 40.2% (86/214) and 34.2% (67/196) within 12 months after diagnosis , respectively. Educational level of college or above (a OR=0.41, 95% CI:0.23-0.71), passive anal sex (a OR=0.40, 95% CI:0.19-0.85), both active and passive anal sex after diagnosis (a OR=0.40, 95% CI:0.20-0.83) and no unprotected oral sex (a OR=0.02, 95% CI:0.01-0.05) were negatively associated with UAI within 12 months after diagnosis. Whereas, not considering necessary to use condom consistently after having repeated undetectable viral load (a OR=3.02, 95% CI:1.37-6.69) was positively associated with UAI within 12 months after diagnosis. Conclusions:Compared with that before diagnosis of HIV infection, although the prevalence of UAI seemed to decrease in HIV-infected MSM in industrial workers after diagnosis, nearly one third of them had high-risk sexual behaviors. Therefore, relevant interventions should be strengthened to reduce high-risk sexual behaviors.

Objective:To explore the cognition of the "undetectable equals untransmittable" ("U=U") concept and associated factors among HIV-infected men who have sex with men (MSM) receiving antiviral treatment (ART) in Shenzhen, and provide evidence for designing promotion and advocacy strategies for the "U=U" concept.Methods:We recruited HIV-infected MSM receiving ART using convenient sampling method combined with routine follow-up in Shenzhen through conducting observational survey. The sample size was estimated to be 475. A questionnaire was administered to collect socio-demographic characteristics, sexual behaviors, ART, viral load testing and the cognition towards "U=U" in HIV-infected MSM. Logistic regression was used to access factors associated with acceptance of "U=U".Results:A total of 490 HIV-infected MSM receiving ART were recruited. Of whom, 60.2% (295/490) were aware of "U=U" and 50.6% (248/490) accepted "U=U". Multiple logistic regression showed that participants who had an educational level of college or above (a OR=1.76,95% CI: 1.12-2.75) were more likely to accept "U=U". Those who had no local residency (a OR=0.51,95% CI: 0.29-0.92), had viral load >0 copies/ml in the last testing (a OR=0.61,95% CI: 0.38-0.98) and were unaware of "U=U" (a OR=0.13, 95% CI: 0.09-0.21), were less likely to accept "U=U". Conclusions:HIV-infected MSM receiving ART had a low cognition level of "U=U" in Shenzhen. Promotion and advocacy on this concept through healthcare workers should be enhanced in combination with routine follow-up in order to improve their ART adherence and outcome of treatment. Furthermore, developing related guidelines on "U=U" according to the characteristics of HIV-infected individuals is warranted to improve the normalization of promotion and advocacy on "U=U".

Objective:To investigate the results of the superficial circumflex iliac artery(SCIA)-based conjoined flap for covering extremely large lower limb defects.Methods:From February 2017 to June 2019, 15 patients were admitted, who suffered from severe degloved injury for the lower limb, including 9 males and 6 females with a median year of 45 (ranged, 36-67 ) years old. All were taken thorough and radical debridement and covered by the VSD device during the emergency operation. The dimension of defects was ranged from 25.0 cm ×8.0 cm to 50.0 cm ×15.0 cm. Using the lower abdominal wall or side chest wall as the donor site, the conjoined flap was dissected when the wound surface became granulating. The perforator match fashions included bilateral SCIA, and ipsilateral SCIA and thoracodorsal artery(TA). The donor sites were primary closure. The follow-up was accomplished by the same surgeon.Results:Fourteen flaps survived completely without significant complications, and distal necrosis was observed in one longitudinal flap, which was healed with the skin graft in the second stage. All flaps were available for a mean follow-up of 18 (ranged 16-24) months. The aesthetic outcomes were achieved on the recipient site without hairy appearance and hyper-pigmentation. A concealed line scare was left on the donor site, without the hernia and limited function. At the last follow-up, 7 cases were excellent and 1 case was good, evaluated with the LEFS criteria. And 6 cases were excellent and 1 case was good, assessed by the AOFAS criteria.Conclusion:The simultaneous reconstruction of extreme lower limb defects and better salvage treatment could be achieved by the SCIA-based conjoined flap. And as a versatile flap, it was blessed with concealed donor site, various design fashions, and larger dissection size in selected cases.