Objective:To investigate the clinical efficacy and safety of deep hyperthermia combined with sintilimab and nab-PC (albumin-bound paclitaxel + carboplatin) regimen in the treatment of advanced squamous non-small cell lung cancer (NSCLC) with driver gene negative and programmed death-1 receptor ligand 1 (PD-L1) expression positive.Methods:A prospective case-control study was performed. A total of 84 advanced squamous NSCLC patients with driver gene negative and PD-L1 expression positive in Hebei Seventh People's Hospital from January 2020 to December 2022 were collected, and all patients were divided into the observation group and the control group according to the random number table method, with 42 cases in each group. The control group was given the treatment of sintilimab combined with nab-PC regimen, and the observation group was given deep hyperthermia on the basis of the control group. After 4 consecutive cycles of treatment, the short-term efficacy of the two groups was compared. The levels of serum tumor markers [carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), cytokeratin fragment 19 (CYFR21-1)], and the positive expression rates of immunohistochemistry markers [p40, p63, and cytokeratin 5/6 (CK5/6)] before and after treatment were compared between two groups. Functional Assessment of Cancer Therapy-Lung cancer module (FACT-L) scores, the adverse reactions and the long-term survival of the two groups were compared.Results:There were 26 males and 16 females in the observation group, and the age was (59±11) years; there were 22 males and 15 females in the control group, and the age was (58±11) years. The objective remission rate and the disease control rate were 71.43% (30/42), 90.48% (38/42), respectively in the observation group, and 50.00% (21/42), 80.95% (34/42), respectively in the control group; the objective remission rate in the observation group was higher than that in the control group, and the difference was statistically significant ( χ2 = 4.04, P = 0.044); and there was no statistically significant difference in the disease control rate of both groups ( χ2 = 1.56, P = 0.212). The levels of serum CEA, SCCA and CYFRA21-1, and the positive expression rates of p40, p63, and CK5/6 in the two groups after treatment were lower than those before treatment (all P < 0.05); and the scores of physiological status, functional status, additional concern in FACT-L scores and the total score of the scale after treatment were higher than those before treatment (all P < 0.05). There were no statistically significant differences in the incidence of adverse reactions including thrombocytopenia, neutropenia, leukopenia, anemia, fever of the two groups (all P > 0.05). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.82-12.75), 5.1 months (95% CI: 3.14-12.26),respectively in the observation group and the control group, and the difference in the median PFS time was statistically significantly of both groups ( χ2 = 4.21, P = 0.040). The median overall survival (OS) time was 12.9 months (95% CI: 6.25-15.46), 9.7 months (95% CI: 4.74-13.02), respectively in the observation group and the control group, and the difference in the median OS time was statistically significantly of both groups ( χ2 = 4.43, P = 0.035). Conclusions:Deep hyperthermia combined with sintilimab and nab-PC regimen in the treatment of advanced squamous NSCLC with driver gene negative and PD-L1 expression positive can effectively reduce the serum tumor markers levels and positive expression rate of immunohistochemical markers, improve the quality of life of patients, and increase the short-term and long-term efficacy.

Objective:To study the common pathogenesis of gout and rheumatoid arthritis(RA)by bioinformatics analysis.Methods:Microarray expression profiles of peripheral blood mononuclear cells in gout and RA were obtained from the GEO public da-tabase.R language and other tools were used to re-annotates the chip,and then the differential genes(DEGs)of the two were screened and the intersection was taken.The protein-protein interaction(PPI)network and topology analysis of common differential genes(CO-DEGs)were constructed by STRING database and Cytoscape software(including CytoNCA plug-in).The HubGene was screened and validated by ROC curve.Finally,the DAVID online analysis tool was used to perform GO and KEGG functional enrichment analysis of HubGene.Results:There were 9 HubGene screened,they were TNF,RGS1,CD69,IL7R,DDX3X,SOCS3,IFIT1,IFIT3,CCL3.GO enrichment showed that HubGene was mainly involves the regulation of virus,STAT receptor signaling pathway and positive regu-lation of neuroinflammatory response.KEGG enrichment showed that HubGene was mainly involved in Toll like receptor signaling pathway,TNF signaling pathway,JAK-STAT signaling pathway,adipocytokine signaling pathway,RIG-Ⅰ-like receptor signaling pathway and osteoclast differentiation.Conclusion:Using bioinformatics analysis,nine HubGene and related signaling pathways in-volved in the pathogenesis of gout and RA have been identified,which may serve as novel biomarkers and potential targets.

Objective To search and evaluate the relevant evidence of blood purification and anticoagulant management of perioperative liver transplantation patients,and to summarize the best evidence,so as to provide evidence-based evidence for clinical blood purification and anticoagulant management practice.Methods Evidence-based questions were determined.Systematic search was conducted on relevant domestic and foreign databases and websites for clinical decisions,guidelines,evidence summaries,system evaluations,and expert consensuses related to blood purification anticoagulation management.The retrieval period is from the establishment to May 2,2023.Literature screening,quality evaluation and evidence summary were conducted by 2 researchers.Results A total of 17 articles were included,including 2 clinical decisions,3 guidelines,2 evidence summaries,4 systematic evaluations and 6 expert consensuses.24 pieces of best evidence were summarized from 6 dimensions,including coagulation function evaluation,anticoagulant strategy,mode selection,vascular access,standardized operation implementation points and personnel organization management.Conclusion The best evidence was summarized in the study on perioperative blood purification and anticoagulant management of liver transplantation,which can provide evidence-based basis for clinical medical staff to implement anticoagulant management.However,it is necessary to further carry out evidence-based practice of perioperative blood purification and anticoagulant management of liver transplantation to verify its anticoagulation effect and nursing safety in clinical practice.

Hypertension heightens the risk of cardiovascular and renal complications in individuals with type 2 diabetes mellitus. Optimal blood pressure (BP) management is crucial for preventing these complications. This review consolidates evidence from clinical trials and major BP management guidelines to shed light on key aspects of hypertension management in diabetes. It addresses BP thresholds to initiate antihypertensive treatment, optimal BP control targets, recommended first-line antihypertensive edications, and BP monitoring plan for the prevention of chronic complications in type 2 diabetes.

Objective:To observe the expression changes of nuclear factor erythroid 2 related factor 2 (Nrf2) and glutathione peroxidase (GPX4) in human pulmonary microvascular endothelial cells (HPMEC) under different experimental conditions, and to explore the role of Nrf2 in inhibiting ferroptosis in the process of alleviating hyperoxic lung injury(HLI).Methods:Hyperoxic model was established by hyperoxia exposure.HPMEC were treated with blank control (control group), oxygen exposure at the concentration of 950 mL/L (hyperoxia group), oxygen exposure at the concentration of 950 mL/L+ 10 μmol/L Ferrostatin (ferroptosis inhibitor group) and oxygen exposure at the concentration of 950 mL/L + 10 μmol/L ML385 (Nrf2 inhibitor group). Cell viability at 24 h and 48 h was tested by the Cell Counting Kit-8 assay, and reactive oxygen species (ROS) levels were detected by a commercial ROS kit.The mRNA and protein levels of Nrf2 and GPX4 were detected by real-time quantitative polymerase chain reaction and Western blot, respectively.Differences were analyzed using the Student′s t-test for a two-group comparison or one-way ANOVA test among groups. Results:(1)Compared with the control group, significantly decreased viability and increased ROS levels were detected in hyperoxia group.Meanwhile, the mRNA (24 h: 0.750±0.010 vs.1.010±0.160, 48 h: 0.690±0.050 vs.1.000±0.070) and protein levels of GPX4 (24 h: 0.160±0.010 vs.0.290±0.010, 48 h: 0.190±0.010 vs.0.250±0.010) at 24 h and 48 h were significantly downregulated, while the mRNA (24 h: 1.740±0.050 vs.1.000±0.050, 48 h: 2.130±0.020 vs.1.000±0.030) and protein levels of Nrf2 (24 h: 0.840±0.010 vs.0.480±0.010, 48 h: 0.840±0.010 vs.0.550±0.030) at 24 h and 48 h were significantly upregulated in hyperoxia group than those of control group (all P<0.05). (2)Compared with the hyperoxia group, significantly increased viability and decreased ROS levels were detected in ferroptosis inhibitor group.Meanwhile, the mRNA (24 h: 1.520±0.110, 48 h: 1.880±0.050) and protein levels of GPX4 (24 h: 0.290±0.010, 48 h: 0.250±0.004) at 24 h and 48 h were significantly upregulated, while the mRNA (24 h: 0.780±0.040, 48 h: 0.760±0.030) and protein levels of Nrf2 (24 h: 0.480±0.010, 48 h: 0.540±0.020) at 24 h and 48 h were significantly downregulated in ferroptosis inhibitor group than those of hyperoxia group (all P<0.05). (3)Compared with the hyperoxia group, significantly decreased viability and increased ROS levels were detected in Nrf2 inhibitor group.Meanwhile, the mRNA (24 h: 0.600±0.030, 48 h: 0.590±0.003) and protein levels of GPX4 (24 h: 0.150±0.001, 48 h: 0.180±0.001) at 24 h and 48 h were significantly downregulated, while the mRNA level of Nrf2 was significantly upregulated at 24 h (3.360±0.130), but downregulated at 48 h (1.430±0.130) (all P<0.05). No significant difference was detected in the protein level of Nrf2 at 24 h and 48 h between hyperoxia group and Nrf2 inhibitor group ( P>0.05). Conclusions:Ferroptosis is involved in the development of HLI, and Nrf2 is able to alleviate hyperoxic lung injury by inhibiting ferroptosis.Therefore, inhibition of ferroptosis by Nrf2 may provide a new therapeutic target for HLI.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.
Humans ; Open Reading Frames ; Peptides ; Glucose ; Genome ; Metabolic Diseases

Objective:To develop a novel, flexible, dual-arm, master-slave digestive endoscopic minimally invasive surgical robot system named dual-arm robotic endoscopic assistant for minimally invasive surgery (DREAMS) and to evaluate its feasibility for endoscopic submucosal dissection (ESD) by using ex vivo porcine stomachs.Methods:A novel endoscopic robot (DREAMS) system was developed which was composed of a flexible two-channel endoscope, two flexible robotic manipulators, a master controller, a robotic arm, and a control system. A total of 10 artificial round-like lesions with diameters ranging from 15 to 25 mm were created (5 in gastric antrum and 5 in gastric body) by using fresh peeled stomach of healthy pigs as the model. Submucosal dissection was performed with the assistance of the DREAMS system by two operators. The main outcome was submucosal dissection speed, and the secondary outcomes included muscular injury rate, perforation rate, and grasping efficiency of the robot.Results:All 10 lesions were successfully dissected en bloc by using the DREAMS system. The diameter of the artificial lesions was 22.34±2.39 mm, dissection time was 15.00±8.90 min, submucosal dissection speed was 141.79±79.12 mm 2/min, and the number of tractions required by each ESD was 4.2 times. Muscular injury occurred in 4/10 cases of ESD. No perforation occurred. Conclusion:The initial animal experiment shows the DREAMS system is safe and effective.

BackgroundElderly cataract patients with depressive symptoms have heavier self-perceived burden， and worse vision-related quality of life compared to patients without depressive symptoms， resulting in the increase of family burden. Most previous studies showed that family relationship and vision were the main factors leading to depression in elderly cataract patients， and ignored the effects of self-feeling and complicated diseases on the psychological state of elderly cataract patients. ObjectiveTo explore the relationship between depressive symptoms， self-perceived burden and postoperative vision-related quality of life in elderly cataract patients， and to analyze the risk factors of depressive symptoms. So as to provide references for targeted psychological intervention in this population. MethodsA total of 104 elderly cataract patients admitted to Jiangsu Province Hospital （The First Affiliated Hospital with Nanjing Medical University） from July 1， 2020 to December 31， 2022 were included. General information， self-perceived burden and postoperative vision-related quality of life were investigated by self-designed questionnaire， Patients' Health Questionnaire depressive Scale-9 item （PHQ-9）， Self-Perceived Burden Scale （SPBS） and National Eye Institute Visual Function Questionnaire-25 （NEI-VFQ-25）. Pearson correlation analysis was performed to analyze the correlation among PHQ-9， SPBS and NEI-VFQ-25 scores. Logistic regression analysis was used to analyze the influencing factors of depressive symptoms in eldery cataract patients. ResultsA total of 100 elderly cataract patients completed an effective questionnaire survey. Among the participants， 31 cases （31.00%） were found to have depressive symptoms. The depressive group exhibited significantly higher SPBS score （t=11.062， P<0.01） and significantly lower NEI-VFQ-25 score （t=-5.235， P<0.01） than those of the non-depressive group. Pearson correlation analysis showed a positive correlation between PHQ-9 and SPBS score （r=0.485， P<0.01）， and a negative correlation between PHQ-9 and NEI-VFQ-25 score （r=-0.440， P<0.01）. Complicated with diabetes （OR=1.441， P<0.01）， osteoarthritis （OR=1.324， P<0.05） and high SPBS score （OR=1.340， P<0.05） were risk factors of depressive sympptoms in elderly cataract patients. ConclusionThe detection rate of depressive symptoms in elderly cataract patients is higher， and postoperative vision-related quality of life in elderly cataract patients complicated with depressive symptoms is poor. Risk factors include diabetes， osteoarthritis and high self-perceived burden. ［Funded by 2022 Jiangsu Province Elderly Health Scientific Research Project （number， LKM2022019）］

Sex difference has shown in the arthritis diseases in human population and animal models. We investigate how the sex and symmetry vary among mouse models with different genomic backgrounds. Disease data of sex and limbs accumulated in the past more than two decades from four unique populations of murine arthritis models were analyzed. They are (1) interleukin-1 receptor antagonist (IL-1ra) deficient mice under Balb/c background (Balb/c KO); (2) Mice with collagen II induced arthritis under DBA/1 background; (3) Mice with collagen II induced arthritis under C57BL/6 (B6) background and (4) A F2 generation population created by Balb/c KO X DBA/1 KO.Our data shows that there is a great variation in sexual dimorphism for arthritis incidence and severity of arthritis in mice harboring specific genetic modifications. For a F2 population, the incidence of arthritis was 57.1% in female mice and 75.6% in male mice. There was a difference in severity related to sex in two populations: B6.DR1/ B6.DR4 (P < 0.001) and F2 (P = 0.023) There was no difference Balb/c parental strain or in collagen-induced arthritis (CIA) in DBA/1 mice. Among these populations, the right hindlimbs are significantly higher than the scores for the left hindlimbs in males (P < 0.05). However, when examining disease expression using the collagen induced arthritis model with DBA/1 mice, sex-dimorphism did not reach statistical significance, while left hindlimbs showed a tendency toward greater disease expression over the right. Sexual dimorphism in disease expression in mouse models is strain and genomic background dependent. It sets an alarm that potential variation in sexual dimorphism among different racial and ethnic groups in human populations may exist. It is important to not only include both sexes and but also pay attention to possible variations caused by disease expression and response to treatment in all the studies of arthritis in animal models and human populations.