[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Objective Methyltransferase 3(METTL3)mediated N6-methyladenosine(m6A)methylation modifica-tion of transient receptor potential cation channel subfamily M member 7(TRPM7)regulates ferroptosis and malig-nant progression in cervical cancer(CESC).Methods Totally 40 patients with cervical cancer were collected.Cer-vical cancer tissues and adjacent normal tissues(≥3 cm from the edge of the tumor tissue)were sampled at opera-tion and then divided into experimental group and control group,respectively.RT-qPCR and Western blot were used to detect the differences in TRPM7 mRNA and protein expression between the two groups.TRPM7-interfering cell lines were constructed to investigate the effects of TRPM7 on CESC cells.Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine(EdU)assay and flow cytometry,respectively.Transwell chamber assays were employed to evaluate cell invasion and migration capabilities.The levels of ferroptosis in CESC cells were measured using kits for reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),and Fe2+.Bioinformatics tools were utilized to predict methyltransferases associated with TRPM7.The interaction between METTL3 and TRPM7 was examined through RNA immunoprecipitation(RIP)and methylated RNA immunoprecip-itation quantitative PCR(Me-RIP qPCR).The effect of METTL3 on the stability of TRPM7 expression was assessed using actinomycin D assay.Results TRPM7 was highly expressed in CESC tissue and cells.Knockdown of TRPM7 significantly inhibited cell proliferation,promoted cell apoptosis,suppressed cell migration and invasion capabilities,and enhanced ferroptosis levels(P＜0.05).Bioinformatics predictions suggested that METTL3 might act as a methyltransferase for TRPM7.Interference with METTL3 gene expression significantly reduced TRPM7 pro-tein levels,decreased TRPM7 m6A modification levels,and impaired TRPM7 gene stability(P＜0.05).Conclusions METTL3 regulates CESC proliferation,apoptosis,migration,invasion,and ferroptosis by m6A meth-ylation modification of the TRPM7 gene.

BACKGROUND:The regulatory mechanisms of acupotomy intervention for knee osteoarthritis at a transcriptome level are not well understood despite its proven clinical efficacy.OBJECTIVE:Using acupotomy therapy in a rat model of knee osteoarthritis,to conduct transcriptome sequencing and bioinformatics analysis on cartilage samples,along with validation,and to reveal the molecular regulatory mechanisms involved in this therapy for knee osteoarthritis in rats.METHODS:Forty-eight Sprague-Dawley rats were selected and divided into three groups by random number table method,acupotomy group,model group,and sham operation group,with 16 rats in each group.Osteoarthritis models were induced by medial meniscus instability in the acupotomy group and model group.After successful modeling,acupotomy group rats were treated with acupotomy once a week,for 4 weeks in total.After the intervention,cartilage samples from the rat's knee joint were stained with hematoxylin-eosin staining and safranin O-fast green staining,evaluated by Mankin scores,and underwent MicroCT scanning.Serum inflammatory factor levels were detected by Elisa.Transcriptome sequencing was performed on the remaining cartilage samples,and the data were analyzed using R software to identify differential gene expression levels among the groups.Core targets were screened through protein-protein interaction network and Cytoscape and validated using RT-qPCR.RESULTS AND CONCLUSION:Compared with the sham operation group,rats in the model group had rough and uneven articular cartilage surfaces,narrowed joint spaces,destroyed articular surface structures,elevated Mankin scores,and significant increases in serum levels of interleukin-6,tumor necrosis factor-α,and matrix metalloproteinase 13(P<0.05).Compared with the model group,rats in the acupotomy group had smoother articular cartilage surfaces,wider joint spaces,slightly irregular articular surfaces,lower Mankin scores,and significantly lower serum levels of interleukin-6,tumor necrosis factor-α,and matrix metalloproteinase-13(P<0.05).Gene ontology and Kyoto genome and genome encyclopedia analyses involved proteolytic metabolism,autophagy,mitogen-activated protein kinase,nuclear factor kB,and Wnt signaling pathways.Protein-protein interaction network and Cytoscape screened for four key genes,including ataxia-telangiectasia mutations,Myb SWIRM and MPN domain protein 1,heat shock protein 90α1,and NIPBL cohesion-loading factor.The mRNA expression of ataxia-telangiectasia mutations,Myb SWIRM and MPN domain protein 1,heat shock protein 90α1,and NIPBL cohesion-loading factor in the articular cartilage of rats in the model group was lower than that of the sham operation group(P<0.05),while the mRNA expression of ataxia-telangiectasia mutations,Myb SWIRM and MPN domain protein 1,heat shock protein 90α1,and NIPBL cohesion-loading factor in the articular cartilage of rats in the acupotomy group was higher than that in the model group(P<0.05).To conclude,acupotomy treatment of knee osteoarthritis in rats may act on signaling pathways such as MAPK,nuclear factor kB,and Wnt to promote cartilage repair,and is closely related to the expression of genes associated with ataxia-telangiectasia mutations,Myb SWIRM and MPN domain protein 1,heat shock protein 90α1,and NIPBL cohesion-loading factor.

Objective:To investigate the clinical efficacy of artificial humeral head replacement versus locking plate internal fixation in the treatment of comminuted proximal humeral fractures in older adult patients. Methods:A total of 30 older adult patients with proximal humeral comminuted fractures, admitted to Beifang Hospital, Huainan Xinhua Medical Group from January 2022 to December 2024, were included in this study. A prospective randomized controlled study design was used. The patients were divided into an observation group and a control group using a random number table method, with 15 patients in each group. The observation group underwent artificial humeral head replacement surgery, while the control group received internal fixation with a proximal humeral locking plate. Clinical treatment outcomes, shoulder joint function recovery, and complications were observed and compared between the two groups.Results:The intraoperative blood loss in the observation group was less than that in the control group [(182.24 ± 24.36) mL vs. (245.17 ± 46.08) mL]. The surgery duration [(71.84 ± 7.52) minutes vs. (93.67 ± 12.50) minutes] and hospital stay [(11.37 ± 1.89) days vs. (13.52 ± 2.67) days] were also significantly shorter in the observation group compared with the control group ( t = 4.68, 5.80, 2.55, all P < 0.05). The range of motion in the shoulder joint was greater in the observation group compared with the control group [forward elevation: (94.47 ± 7.66) ° vs. (86.14 ± 5.15) °, external rotation: (61.35 ± 6.57) ° vs. (52.40 ± 4.82) °, and internal rotation: (74.35 ± 4.80) ° vs. (62.76 ± 3.59) °]. The total Constant-Murley score was higher in the observation group [(92.91 ± 10.58) vs. (76.29 ± 7.48)], and the rate of excellent recovery of shoulder function was also higher in the observation group [73.33% (11/15) vs. 53.33% (8/15)] compared with the control group. The incidence of complications was lower in the observation group [6.66% (1/15) vs. 33.33% (5/15)] compared with the control group. All differences were statistically significant ( t = 3.50, 4.25, 7.49, 4.97, χ2 = 4.12, 5.12, all P < 0.05). Conclusions:For older adult patients with severe osteoporosis or irreparable proximal humeral comminuted fractures, artificial humeral head replacement yields more favorable outcomes compared with locking plate internal fixation, resulting in a better recovery of shoulder joint function.

BACKGROUND:The regulatory mechanisms of acupotomy intervention for knee osteoarthritis at a transcriptome level are not well understood despite its proven clinical efficacy.OBJECTIVE:Using acupotomy therapy in a rat model of knee osteoarthritis,to conduct transcriptome sequencing and bioinformatics analysis on cartilage samples,along with validation,and to reveal the molecular regulatory mechanisms involved in this therapy for knee osteoarthritis in rats.METHODS:Forty-eight Sprague-Dawley rats were selected and divided into three groups by random number table method,acupotomy group,model group,and sham operation group,with 16 rats in each group.Osteoarthritis models were induced by medial meniscus instability in the acupotomy group and model group.After successful modeling,acupotomy group rats were treated with acupotomy once a week,for 4 weeks in total.After the intervention,cartilage samples from the rat's knee joint were stained with hematoxylin-eosin staining and safranin O-fast green staining,evaluated by Mankin scores,and underwent MicroCT scanning.Serum inflammatory factor levels were detected by Elisa.Transcriptome sequencing was performed on the remaining cartilage samples,and the data were analyzed using R software to identify differential gene expression levels among the groups.Core targets were screened through protein-protein interaction network and Cytoscape and validated using RT-qPCR.RESULTS AND CONCLUSION:Compared with the sham operation group,rats in the model group had rough and uneven articular cartilage surfaces,narrowed joint spaces,destroyed articular surface structures,elevated Mankin scores,and significant increases in serum levels of interleukin-6,tumor necrosis factor-α,and matrix metalloproteinase 13(P<0.05).Compared with the model group,rats in the acupotomy group had smoother articular cartilage surfaces,wider joint spaces,slightly irregular articular surfaces,lower Mankin scores,and significantly lower serum levels of interleukin-6,tumor necrosis factor-α,and matrix metalloproteinase-13(P<0.05).Gene ontology and Kyoto genome and genome encyclopedia analyses involved proteolytic metabolism,autophagy,mitogen-activated protein kinase,nuclear factor kB,and Wnt signaling pathways.Protein-protein interaction network and Cytoscape screened for four key genes,including ataxia-telangiectasia mutations,Myb SWIRM and MPN domain protein 1,heat shock protein 90α1,and NIPBL cohesion-loading factor.The mRNA expression of ataxia-telangiectasia mutations,Myb SWIRM and MPN domain protein 1,heat shock protein 90α1,and NIPBL cohesion-loading factor in the articular cartilage of rats in the model group was lower than that of the sham operation group(P<0.05),while the mRNA expression of ataxia-telangiectasia mutations,Myb SWIRM and MPN domain protein 1,heat shock protein 90α1,and NIPBL cohesion-loading factor in the articular cartilage of rats in the acupotomy group was higher than that in the model group(P<0.05).To conclude,acupotomy treatment of knee osteoarthritis in rats may act on signaling pathways such as MAPK,nuclear factor kB,and Wnt to promote cartilage repair,and is closely related to the expression of genes associated with ataxia-telangiectasia mutations,Myb SWIRM and MPN domain protein 1,heat shock protein 90α1,and NIPBL cohesion-loading factor.

Objective:To investigate the clinical efficacy of artificial humeral head replacement versus locking plate internal fixation in the treatment of comminuted proximal humeral fractures in older adult patients. Methods:A total of 30 older adult patients with proximal humeral comminuted fractures, admitted to Beifang Hospital, Huainan Xinhua Medical Group from January 2022 to December 2024, were included in this study. A prospective randomized controlled study design was used. The patients were divided into an observation group and a control group using a random number table method, with 15 patients in each group. The observation group underwent artificial humeral head replacement surgery, while the control group received internal fixation with a proximal humeral locking plate. Clinical treatment outcomes, shoulder joint function recovery, and complications were observed and compared between the two groups.Results:The intraoperative blood loss in the observation group was less than that in the control group [(182.24 ± 24.36) mL vs. (245.17 ± 46.08) mL]. The surgery duration [(71.84 ± 7.52) minutes vs. (93.67 ± 12.50) minutes] and hospital stay [(11.37 ± 1.89) days vs. (13.52 ± 2.67) days] were also significantly shorter in the observation group compared with the control group ( t = 4.68, 5.80, 2.55, all P < 0.05). The range of motion in the shoulder joint was greater in the observation group compared with the control group [forward elevation: (94.47 ± 7.66) ° vs. (86.14 ± 5.15) °, external rotation: (61.35 ± 6.57) ° vs. (52.40 ± 4.82) °, and internal rotation: (74.35 ± 4.80) ° vs. (62.76 ± 3.59) °]. The total Constant-Murley score was higher in the observation group [(92.91 ± 10.58) vs. (76.29 ± 7.48)], and the rate of excellent recovery of shoulder function was also higher in the observation group [73.33% (11/15) vs. 53.33% (8/15)] compared with the control group. The incidence of complications was lower in the observation group [6.66% (1/15) vs. 33.33% (5/15)] compared with the control group. All differences were statistically significant ( t = 3.50, 4.25, 7.49, 4.97, χ2 = 4.12, 5.12, all P < 0.05). Conclusions:For older adult patients with severe osteoporosis or irreparable proximal humeral comminuted fractures, artificial humeral head replacement yields more favorable outcomes compared with locking plate internal fixation, resulting in a better recovery of shoulder joint function.

Objective To understand the reliability of caloric test results through the analysis of the pod shape dia-gram types of caloric test and to provide a more accurate and reliable basis for vestibular system function evaluation.Meth-ods The results of caloric test in 528 patients from July 2021 to May 2022 in vertigo diagnosis and treatment center were analyzed.According to pod pattern and unilateral weakness(UW),the patients were divided into five groups:cold and warm test symmetrical group,left and right side asymmetry group,single value significant abnormal group,bilateral hypo-plasia group and pod morphology unable to be classified group.Unreliable data can be identified by comparing,explaining,and summarizing the results of UW of different groups,so as to reduce the interference of unreliable data to clinical diagno-sis and treatment.Results Cold and warm test symmetric group(n=439)included patients with symmetry of bilateral vestibular function(n=273)and decreased vestibular function of one side(n=166).Left and right symmetrical groups in-eluded pationts with bilateral symmetric vestibular function(n=11)and unilateral reduction(n=13).Single value signifi-cant abnormal group showed cases with unilateral vestibular function reduction(n=25)and bilateral symmetric vestibular function(n=11).Bilateral hypolasion group showed cases with bilateral symmetric vestibular function(n=25)and unilat-eral reduction(n=9).Pod morphology unclassified group(n=5)suggested varions interference factors.Conduson When the function of the peripheral vestibular is symmetrical and normal,we should be alert to the existence of temperature effect,and should consider the inspection of the perfusion apparatus and the calibration of the irrigation temperature.When the function of the peripheral vestibular shows unilateral weakness,repeating the irrigation is recommended when the single value of the caloric test significantly increases or decreases.If there is no change,repeating the irrigation at the same tem-perature in the other ear or even repeating the whole caloric test are recommended.The UW value could not truly reflect the state of peripheral vestibular function when the caoric test produces bilateral weakness.Therefore,water irrigation could be used to make a correct judgment based on the medical history and other auxiliary examinations.It is of great significance to judge the effectiveness of caloric test comprehensively by combining the morphology of pod diagram with UW value.

Background Chronic intermittent hypobaric hypoxia (CIHH) can effectively alleviate type 2 diabetes mellitus (T2DM). In this process, the underlying mechanism in its association with the epigenetic regulation of DNA methylation in the promoter regions of glucose metabolism key enzyme genes remains unclear yet. Objective To investigate the effects of CIHH on expression and promoter region methylation of key enzyme genes related to glucose metabolism in diabetes mice, and to explore the underlying mechanism by which CIHH regulates glucose metabolism. Methods Forty C57BL/6J male mice were divided randomly into a normobaric normoxic control (NN/CON) group, a chronic intermittent hypobaric hypoxia intervention control (CIHH/CON) group, a normobaric normoxic diabetic model (NN/DM) group, and a chronic intermittent hypobaric hypoxia intervention diabetic model (CIHH/DM) group. The mice in the NN/DM and the CIHH/DM groups were fed for 7 weeks with high-fat and high-sugar diet. Subsequently, these mice were intraperitoneally injected consecutively with 50 mmol·L⁻¹ streptozotocin (STZ) for 5 d at a dose of 40 mg·kg⁻¹ (body weight) per day to create T2DM model mice. The mice in the CIHH/DM and the CIHH/CON groups were intervened by simulating hypobaric hypoxia at 5000 m altitude for 6 h per day, while the mice in the NN/DM and the NN/CON groups were always placed in a normobaric normoxic environment. All mice were continuously treated for 4 weeks, and blood glucose were monitored during this period. After the CIHH intervention experiment, the glucose tolerance and insulin sensitivity of mice were evaluated. A set of indicators involved in key glycolytic enzymes glucokinase (GK) and pyruvate kinase (PK), as well as key gluconeogenic enzymes phosphoenolpyruvate carboxyl kinase (PEPCK) and glucose-6-phosphatase (G6P) were measured in the liver of mice, including enzyme activity, relative mRNA expression level, and DNA methylation level in the gene promoter regions. Results Compared with the mice in the NN/DM group, the blood glucose levels of the mice in the CIHH/DM group decreased after the 25^th day of the CIHH intervention (P<0.05). Regarding the diabetic glucose tolerance curves, the area under the curve (AUC) of the mice in the CIHH/DM group was lower than that of the NN/DM group (P<0.05). Compared with the mice in the NN/DM group, the mice in the CIHH/DM group showed that the serum insulin content and HOMA of insulin resistance index (HOMA-IRI) decreased (P<0.05), the enzyme activities of GK and PK increased and the relative mRNA expression levels of their genes were up-regulated (P<0.05), while the enzyme activities of PEPCK and G6P decreased and the relative mRNA expression levels of their genes were down-regulated (P<0.05) in liver. The average DNA methylation levels in the promoter regions of GK, PK, PEPCK, and G6P genes in liver of mice in each group were not significantly different (P>0.05), and their correlations with mRNA expression levels were also not statistically significant (P>0.05). Conclusion CIHH intervention may reduce blood glucose level, improve glucose tolerance, alleviate insulin resistance, and regulate the key enzyme activities of glucose metabolism and the relative mRNA expression of their corresponding genes in T2DM mice, but the above phenomena are not related to the DNA methylation levels in the promoter regions of these key enzymes.

Background::Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women.Methods::Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.Results::Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women ( Pfor trend <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25-1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20-1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives’ hypertension, with adjusted ORs of 1.28 (95% CI: 1.25-1.31), 1.19 (95% CI: 1.17-1.21), and 1.28 (95% CI: 1.26-1.31), respectively. Conclusion::Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.

Objectives: . Considerable research has been focused on independent predictors of difficult laryngeal exposure (DLE) during suspension laryngoscopy. However, previous studies have yielded inconsistent results and conclusions. Consequently, we performed a meta-analysis of the existing literature with the aim of identifying significant parameters for a standardized preoperative DLE prediction system. Methods: . We systematically retrieved articles from the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases up to October 2022. Data from eligible studies were extracted and analyzed using the R programming language. The effect measures included odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous variables and mean differences (MDs) with 95% CIs for continuous variables. Results: . The search yielded 1,574 studies, of which 18 (involving a total of 2,263 patients) were included. Pooled analysis demonstrated that patients with DLE during microsurgery tended to be male (OR, 1.73; 95% CI, 1.16–2.57); were older (MD, 5.47 years, 95% CI, 2.44–8.51 years); had a higher body mass index (BMI; MD, 1.19 kg/m2; 95% CI, 0.33–2.05 kg/m2); had a greater neck circumference (MD, 2.50 cm; 95% CI, 1.56–3.44 cm); exhibited limited mouth opening (MD, −0.52 cm; 95% CI, −0.88 to −0.15 cm); had limited neck flexibility (MD, −10.05 cm; 95% CI, −14.10 to −6.00 cm); displayed various other anatomical characteristics; and had a high modified Mallampati index (MMI) or test score (OR, 3.37; 95% CI, 2.07–5.48). Conclusion . We conducted a comprehensive and systematic analysis of the factors relevant to DLE. Ultimately, we identified sex, age, BMI, neck circumference, MMI, inter-incisor gap, hyomental distance, thyromental distance, sternomental distance, and flexion-extension angle as factors highly correlated with DLE.