[摘 要] 目的：探讨程序性死亡蛋白1（PD-1）抑制剂与恶性黑色素瘤患者癌性疲劳（CRF）之间的关系及其影响因素。方法：选取2019年4月至2024年4月期间在济南市人民医院接受治疗的100例恶性黑色素瘤患者作为研究对象，使用中文版Piper疲劳量表评估这些患者在接受首次PD-1抑制剂治疗前后3个月内的疲劳状况。结果：使用PD-1抑制剂前后的患者疲劳评分存在显著差异（P < 0.001）。单变量分析发现，性别、吸烟史、肿瘤位置以及使用的PD-1抑制剂类型对于疲劳程度没有明显影响（均P > 0.05），而与年龄、疾病分期、贫血状态、白细胞减少症、继发性甲状腺机能减退（甲减）、继发性肾上腺皮质醇功能减退（AI）、继发性促肾上腺皮质激素降低（P < 0.05或P < 0.01或P < 0.001）相关联。进一步的多变量回归分析揭示，继发性甲减、继发性AI、贫血、白细胞减低是导致此类患者出现严重CRF的关键独立风险因素（均P < 0.05）。结论: PD-1抑制剂的不良反应继发性甲减、继发性AI、贫血、白细胞减低是恶性黑色素瘤患者CRF的独立风险因素。

Objective To understand the composition of death causes of residents in Tianzhu Tibetan Autonomous County,Wuwei City,and to analyze the current situation of life expectancy and life loss of residents,so as to provide evidence for disease control and health promotion.Methods According to the international classification of diseases(ICD-10),the population data and death cause monitoring data of Tianzhu Tibetan Autonomous County in 2021 were analyzed,standardized with the data of the seventh national census,and analyzed with SPSS 21.0 software and life expectancy statistics.Results The crude mortality rate of residents in Tianzhu Tibetan Autonomous County was 642.25/100 000,The male crude mortality(727.12/100 000)rate was higher than the female(553.29/100 000).The overall life expectancy was 79.07 years.The life expectancy in males was 76.77 years and the life expectancy in females was 81.47 years.The first five causes of death were circulatory system(mortality 270.14 per 100,000),nervous system(mortality 159.57 per 100,000),malignant tumor(mortality 101.97 per 100,000),respiratory system(mortality 27.81 per 100,000)and gastrointestinal disease disease(mortality 26.48 per 100,000).The first five places of AYLL were injury and poisoning(24.81 years/person),spirit and blood(15.42 Years/person),infectious diseases(13.06 years/person),malignant tumor(11.78 Years/person)and urogenital diseases(9.94 years/person).Conclusion The highest mortality rate in the 2021 Bairi Tibetan Autonomous County was circulatory system disease,and the major causes of premature death were injury and poisoning.

Objective To investigate the role of Taraxasterol(TAR)on ferroptosis in chondrocytes induced by Erastin.Methods The C28/I2 chondrocyte line was treated with Erastin to construct the ferroptosis model of chon-drocytes in vitro and the experiments were divided into Control,Erastin,TAR,and TAR+Erastin groups.Cell via-bility was detected by the CCK-8 assay.Cytotoxicity was detected by the lactate dehydrogenase(LDH)kit and the Calcein/PI cytokinesis kit.Flow cytometry was used to detect lipid reactive oxygen species(ROS).The intracellular glutathione(GSH)content was detected by GSH kit.Mitochondrial membrane potential was detected by JC-1 stai-ning and RH123 staining.ACSL4 and GPX4 protein expression and the key indicators of ferroptosis were detected by Western blot.Results TAR restored the decreased cell viability of C28/I2 chondrocytes induced by Erastin treatment as well as reduced Erastin-induced cytotoxicity(P＜0.01).Compared with the control group,the level of intracellular lipid ROS increased(P＜0.01)and the content of GSH decreased(P＜0.01)after treatment with Erastin,while TAR could reduce the production of lipid ROS(P＜0.01)and increase the content of GSH(P＜0.01).TAR restored mitochondrial membrane potential in C28/I2 chondrocytes ferroptosis,decreased ACSL4 pro-tein expression(P＜0.01)and increased GPX4 protein expression(P＜0.01).In addition,TAR restored the re-duced cell viability caused by IL-1 β treatment.Conclusion TAR can inhibit Erastin induced ferroptosis in C28/I2 chondrocytes,which may be related to the regulation of ACSL4 and GPX4 protein expression.

The current linear economy model relies on fossil energy and increases CO₂ emissions, which contributes to global warming and environmental pollution. Therefore, there is an urgent need to develop and deploy technologies for carbon capture and utilization to establish a circular economy. The use of acetogens for C1-gas (CO and CO₂) conversion is a promising technology due to high metabolic flexibility, product selectivity, and diversity of the products including chemicals and fuels. This review focuses on the physiological and metabolic mechanisms, genetic and metabolic engineering modifications, fermentation process optimization, and carbon atom economy in the process of C1-gas conversion by acetogens, with the aim to facilitate the industrial scale-up and carbon negative production through acetogen gas fermentation.
Fermentation ; Gases/metabolism* ; Carbon Dioxide/metabolism* ; Metabolic Engineering ; Carbon/metabolism*

Abstract: Objective　The study aims to investigate the diagnosis quality and accuracy of syphilis cases reported by medical facilities in Inner Mongolia, understand possible problems and influencing factors in reporting and diagnosis, providing evidence for the better formulation of syphilis control and prevention. Methods　Cross-sectional survey was conducted with 2 counties sampled randomly from 12 municipals of Inner Mongolia, different medical facilities were covered. Syphilis cases reported from July 2019 to June 2020 in medical institutions of different categories were sampled and checked. The quality and accuracy of syphilis case reporting were evaluated according to the identifiers in "Syphilis Diagnosis (WS 273-2018)" and "National STD Case Reporting Quality Management Scheme (2018)". In addition, the basic information of medical institutions and the implementation of syphilis detection in laboratories were investigated, and the physicians who reported the case first were interviewed to understand their mastery of syphilis diagnosis and reporting, thus analyzing the major factors influencing the accuracy of reports. Results　The reporting rate of syphilis in medical institutions in Inner Mongolia was 99.04% (311/314), the missing-report rate was 0.96% (3/314), the timely reporting rate was 98.05% (1 659/1 692), the completeness rate was 99.64% (1 686/1 692), the correct rate was 99.35% (1 681/1 692), the accuracy rate of internet-based input was 84.63% (1 432/1 692). There were statistical differences in the quality (χ2=13.95, P<0.05; χ2=11.40, P<0.05) and accuracy （χ2=30.06, P<0.05; χ2=44.93, P<0.05) of reports among different municipals and different types of medical facilities. The accuracy rate of syphilis reporting by medical institutions was 86.17% (1 458/1 692), the correct rate for classifying diagnosis was 87.06% (1 473/1 692), and the accuracy rate of staging was 90.25% (1 527/1 692). Multivariate logistic regression results showed that whether the first-clinic physician attended training in the past three years [OR=6.26, 95%CI: (2.12-18.46)] and whether they grasped the key points of syphilis classification standard [OR=2.79, 95%CI: (1.21-6.46)] influenced report accuracy. Conclusions　The quality of reports in Inner Mongolia medical institutions is generally high, but the accuracy rate of reporting and correctness of network input have not yet reached the target requirement of 95%. There is still room for improvement in reporting and diagnostic capabilities. It is suggested to further strengthen the training frequency and coverage for physicians on syphilis diagnosis standard.

IL-34 can promote osteoclast differentiation and activation, which may contribute to steroidinduced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.

Objective:To investigate the risk factors for biochemical recurrence after radical prostatectomy.Methods:The clinical data of 558 radical prostatectomy patients admitted to the First Affiliated Hospital of Air Force Military Medical University from January 2010 to December 2020 were retrospectively analyzed. The average age was 67.9 (40-87) years old, and the average body mass index was 24.56 (15.12-35.94) kg/m 2. The average PSA was 41.07 ng/ml, including 48 cases<10 ng/ml, 98 cases 10-20 ng/ml, and 412 cases>20 ng/ml. There were 123, 214, 118, 89, and 14 cases with biopsy Gleason 6-10 score, respectively. The clinical stage : 90 cases in ≤T 2b, 273 cases in T 2c, and 195 cases in ≥T 3 . 558 cases underwent radical prostatectomy, including 528 robotic-assisted laparoscopic surgery, 25 laparoscopic surgery, and 5 open-surgery. The risk factors for postoperative biochemical recurrence were analyzed by Cox regression. Results:A total of 63 patients had postoperative pathological stage pT 2a, 32 patients had pT 2b, 241 patients had pT 2c, and 222 patients had ≥pT 3. A total of 210 cases developed biochemical recurrence after surgery, and the mean time to biochemical recurrence was 33.3 (3-127) months after the radical prostatectomy. The biochemical recurrence rates at 1, 3, and 5 years were 9.7% (54/558), 21.5% (120/558), and 31.7% (177/558), respectively. Among pT 2a and pT 2b patients, 7 (11.1%) and 4 (12.5%) cases developed biochemical recurrence, respectively. Among pT 2c stage patients, 145 (60.17%) cases had positive cut margins, treated with androgen-deprivation therapy (ADT) after surgery. 68 (28.21%) cases of pT 2c stage patients had biochemical recurrence at mean 36.1 (3-106)months after the radical prostatectomy. Among ≥pT 3 patients, 147 patients with positive margins, perineural invasion, seminal vesicle invasion and positive pelvic lymph nodes were treated with postoperative androgen deprivation therapy (ADT) + radiotherapy. 98 of 147 patients (66.67%) had biochemical recurrence, and the average time to biochemical recurrence was 30.6 (24-98) months.75 patients of ≥pT 3 without positive margins, perineural invasion, seminal vesicle invasion or positive pelvic lymph nodes, were treated with postoperative ADT. 33 of them (44%) had biochemical recurrence, and the average time to biochemical recurrence was 32.5 (21-106) months. 5-and 10-year survival rates of 210 patients with biochemical recurrence were 89.05% (187/210) and 78.09% (164/210) respectively, 5- and 10-year tumor-specific survival rates were 92.57% and 87.69%, respectively. 46 of 210 cases died, of which 31 (67.39%) died from prostate cancer, and 15 cases (32.61%) died from cardiovascular and cerebrovascular diseases. Multifactorial Cox regression analysis showed that patient's age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7 were independent risk factors for biochemical recurrence. Conclusions:After radical prostatectomy, patients were treated according to their pathological stage and surgical margins. Patients with positive margins have a higher risk of biochemical recurrence. The independent risk factors for biochemical recurrence included age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7.

Objective:To explore the effects of operation timing on postoperative complications and operative duration in children undergoing non-emergency operation for femoral neck fracture.Methods:Fifty-nine children and adolescents with femoral neck fracture were retrospectively analyzed who had been admitted to Department of Pediatric Orthopedics, Zhengzhou Orthopedic Hospital Affiliated to Henan University from February, 2015 to September, 2019. They were 39 boys and 20 girls with a mean age of 11.7 (7.1, 13.7) years. By Delbet fracture classification, 7 cases were type Ⅰ, 27 cases type Ⅱ, 20 cases type Ⅲ, and 5 cases type Ⅳ. The patients were divided into 4 groups by the time from injury to operation (TFITO): 17 cases were assigned into group A with TFITO from 24 to 48 hours, 14 cases into group B with TFITO from 49 to 72 hours, 12 cases into group C with TFITO from 73 to 96 hours, and 16 cases into group D with TFITO>96 hours. The effects of TFITO on postoperative complications and operative duration were analyzed.Results:There were no significant differences between the 4 groups in their preoperative general data, showing they were comparable ( P>0.05). This cohort was followed up for 12 to 62 months (average, 20 months). The operation time was not included for this study in 6 cases whose associated injury had to be treated simultaneously. The median operation time for the other 53 patients was 80 (70, 105) min. The correlation coefficient between TFITO and operation time was 0.098 ( P=0.484). Postoperative complications occurred in 37.3% of the patients (22/59), including 14 cases of avascular necrosis of femoral head. For groups A, B, C and D, the incidences of complications were 47.1% (8/17), 50.0% (7/14), 25.0% (3/12) and 25.0% (4/16) while the incidences of avascular necrosis of femoral head 23.5% (4/17), 31.3% (5/16), 16.7% (2/12) and 18.8% (3/16), showing insignificant differences between the 4 groups in all the comparisons ( P>0.05). Conclusion:The time from injury to operation may not increase operative duration or postoperative complications such as avascular necrosis of femoral head in children undergoing non-emergency operation for femoral neck fracture.

Objective:A new measurement index, femoral neck-lesser trochanter anteversion (FN-LTA), is proposed. To explore the feasibility and advantage of applying the FN-LTA to evaluate the proximal femoral deformity of unilateral developmental dislocation of the hip in children, so as to solve the current clinical problems.Methods:The imaging data of 90 patients with unilateral DDH admitted to our department from February 2016 to April 2017 were retrospectively analyzed, There were 13 males and 77 females. The age ranged from 0.6 to 11 years, with an average of 2.6±2.3 years. Femoral neck anteversion (FNA) and FN-LTA were measured at the affected and healthy sides. Analyze the correlation between FN-LTA and FNA, analyze the influence of gender, age, side, dislocation degree and other factors on FN-LTA, compare the difference between the affected side and the healthy side of FNA, FN-LTA, and analyze the influence of dislocation degree on this difference, compare the diagnostic efficacy and intra group consistency of FNA and FN-LTA. The possible advantages of FN-LTA in clinical application were preliminarily analyzed.Results:There was a positive correlation between FN-LTA and FNA in both healthy and affected sides (healthy side r=0.217, P=0.040, affected side r=0.298, P=0.004). FNA and FN-LTA in the affected side of DDH children were both larger than the healthy side, FNA affected side 38.86°±11.70°, healthy side 35.44°±11.16°; FN-LTA affected side 72.19°±9.17°, healthy side 61.17°±10.30°. The difference had statistical significance. FN-LTA was not affected by gender, side, degree of dislocation and other factors (gender P=0.060, side P=0.550, degree of dislocation of healthy side P=0.130, affected side P=0.705), but negatively correlated with age (healthy side r=-0.261, P=0.013, affected side r=-0.287, P=0.006). The diagnostic efficiency of FN-LTA is better, AUC FNA=0.561, AUC FN-LTA=0.736 ( P<0.05). FN-LTA and FNA had excellent intra group and inter group consistency. Inter group ICCFNA=0.956, ICCFN-LTA=0.973; intra group ICCFNA1=0.937, ICCFNA2=0.893, ICCFN-LTA1=0.887, ICCFN-LTA2=0.874. With the increase of dislocation degree, the difference between FNA and FN-LTA decreased. This decreasing trend was statistically significant in FNA ( P=0.030) but not in FN-LTA ( P=0.180). Conclusion:FN-LTA is a reliable method with a higher degree of differentiation for the assessment of anteverted deformity in DDH children' proximal end of femur, the measured data are more capable of guiding the rotation of osteotomy.

Objective Breast cancer is one of the deadliest malignancies in the world. ebracteolatain A (EA) is a kind of acetylphloroglucinol extracted from ebracteolatain. To explore the specific mechanism of EA inhibiting the proliferation of breast cancer cell MCF-7, so as to provide a new approach for the clinical treatment of breast cancer. Methods EA with different concentrations were added to breast cancer cell MCF-7 to detect changes in PKD1 protein expression. The plasmid with overexpressed PKD1 was constructed and transfected into cells, and the mRNA and protein expression levels of PKD1 were detected by real-time fluorescence quantitative PCR and Western Blot assay. CCK-8 assay was used to detect changes in cell proliferation capacity. Western Blot assay was used to detect the expression level of PKD1 and its related signaling pathways. Results EA inhibited the expression of PKD1 protein in breast cancer cells with a dose-dependent manner (P< 0.05). When transfected with the overexpressed plasmid, PKD1 was significantly increased in mRNA and protein levels (P<0.001). At the same time, PKD1 overexpression significantly reversed inhibition of EA on MCF-7 proliferation (P<0.001). It was confirmed by signaling pathway analysis that EA might affect the proliferation ability of breast cancer cells by inhibiting PKD1-mediated MEK/ERK and PI3K/AKT signaling activity (P<0.05). Conclusion EA could inhibit the proliferation of breast cancer cells by regulating PKD1-mediated MEK/ERK and PI3K/AKT signaling pathways.