Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective:To systematically evaluate the effect of the Dietary Approaches to Stop Hypertension (DASH) diet on common metabolic diseases.Methods:Following the PICOS framework to construct the search formula, we systematically searched the Web of science, PubMed, Cochrane Library, CNKI, Wanfang, and VIP databases for randomized controlled trials (RCTs) investigating the effect of the DASH diet on multiple metabolic indices including body weight, body mass index (BMI), fasting blood glucose, triglycerides, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in patients with metabolic disorders (e.g., obesity, diabetes mellitus, and hypertension) published both in China and abroad from 1 January 2000 to 31 December 2023. The search terms were combinations of MeSH and free-text terms, and the raw data obtained from the search were screened according to the inclusion and exclusion criteria to determine the articles that were finally included in the analysis. The differences in these metabolic indices were compared between the intervention group group (using DASH diet) and the control group. The quality of the studies was assessed quantitatively using the modified Jadad scale and qualitatively using the Risk of Bias 2 (RoB 2) tool by two reviewers independently. Data analysis was conducted using Stata 18.0 software, with the I 2 test for heterogeneity evaluation and funnel plots for qualitative assessment of publication bias. Results:A total of 13 RCTs were included, involving 1 653 participants. Meta-analysis showed that the intervention group had more favorable effects on SBP ( SMD:-0.91, 95%CI: -1.55–-0.27; Z=-2.79, P<0.005) and DBP ( SMD: -0.98, 95%CI: -1.62–-0.33; Z=-2.96, P<0.05) than the control diet. Fasting blood glucose ( SMD: 0.21, 95% CI: 0.01–0.41; Z=2.06, P=0.04) was statistically significant. There were no significant differences in body weight, BMI, fasting blood glucose, and triglyceride outcomes betweeen these two groups. Conclusions:DASH diet is effective in controlling SBP and DBP in patients with metabolic disorders and may be useful in clinical adjunctive therapy. However, current evidence does not support an independent improvement in glycolipid metabolic markers.

Objective:To systematically evaluate the effect of the Dietary Approaches to Stop Hypertension (DASH) diet on common metabolic diseases.Methods:Following the PICOS framework to construct the search formula, we systematically searched the Web of science, PubMed, Cochrane Library, CNKI, Wanfang, and VIP databases for randomized controlled trials (RCTs) investigating the effect of the DASH diet on multiple metabolic indices including body weight, body mass index (BMI), fasting blood glucose, triglycerides, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in patients with metabolic disorders (e.g., obesity, diabetes mellitus, and hypertension) published both in China and abroad from 1 January 2000 to 31 December 2023. The search terms were combinations of MeSH and free-text terms, and the raw data obtained from the search were screened according to the inclusion and exclusion criteria to determine the articles that were finally included in the analysis. The differences in these metabolic indices were compared between the intervention group group (using DASH diet) and the control group. The quality of the studies was assessed quantitatively using the modified Jadad scale and qualitatively using the Risk of Bias 2 (RoB 2) tool by two reviewers independently. Data analysis was conducted using Stata 18.0 software, with the I 2 test for heterogeneity evaluation and funnel plots for qualitative assessment of publication bias. Results:A total of 13 RCTs were included, involving 1 653 participants. Meta-analysis showed that the intervention group had more favorable effects on SBP ( SMD:-0.91, 95%CI: -1.55–-0.27; Z=-2.79, P<0.005) and DBP ( SMD: -0.98, 95%CI: -1.62–-0.33; Z=-2.96, P<0.05) than the control diet. Fasting blood glucose ( SMD: 0.21, 95% CI: 0.01–0.41; Z=2.06, P=0.04) was statistically significant. There were no significant differences in body weight, BMI, fasting blood glucose, and triglyceride outcomes betweeen these two groups. Conclusions:DASH diet is effective in controlling SBP and DBP in patients with metabolic disorders and may be useful in clinical adjunctive therapy. However, current evidence does not support an independent improvement in glycolipid metabolic markers.

Objective:To investigate the effect of internal fixation of medial support and lateral wall on initial weight-bearing stability of femoral intertrochanteric fracture after reconstruction of intertrochanteric fracture.Methods:Based on the digital model of Sawbones femur, intertrochanteric fracture models with different medial support and lateral wall states were constructed. Combined with various intramedullary and extramedullary fixation methods, the mechanical models after fixation were simplified, and seven mechanical simplified models were obtained. The individual body weight load (70 kg) was simulated by applying concentrated force (700 N) to the end nodes of the femoral head. Through the analysis and calculation of each model in StrucMaster software, the axial force, shear force, bending moment, displacement deformation, and support reaction force of each bar in each mechanical model were obtained, and the results were output through the supporting SMConsole.Results:The median bending moment of model 1 was 11.55(5.57, 18.00) N·m, and the median bending moment was 2.89(2.81, 2.94) rad. The median bending moment of model 2 was 13.72(9.30, 20.05) N·m, and the median bending moment was 2.93(2.77, 3.05) rad. The median bending moment of model 3 was 19.65(10.23, 26.11) N·m, and the median bending moment was 2.93 (2.77, 3.05) rad. The median bending moment of model 4 was 25.95(25.14, 36.70) N·m, and the median bending moment was 4.38(3.16, 5.15) rad. The median bending moment of model 5 was 13.66(7.99, 25.62) N·m, and the median bending moment was 3.50(3.32, 3.56) rad. The median bending moment of model 6 was 24.60(9.33, 29.37) N·m, and the median bending moment was 3.90(3.69, 4.10) rad. The median bending moment of model 7 was 41.14(0.16, 41.30) N·m, and the median bending moment was 5.50(5.50, 7.05) rad. The mechanical properties of model 1 were better than those of the other six models.Conclusion:The simplified mechanical model and its mechanical calculation analysis based on the lever reconstruction balance theory can be used to preliminarily reveal the mechanical characteristics of femoral intertrochanteric fractures after internal fixation. The internal fixation methods of the medial support and lateral wall of femoral intertrochanteric fracture reconstruction can improve the initial stability of the weight bearing after internal fixation of femoral intertrochanteric fractures and have guiding significance for the functional rehabilitation of early postoperative weight bearing.

With the development of modern medical standards,autoimmune diseases and their associ-ated successive osteoporosis have received increasing attention in recent years.Patients with autoimmune diseases,due to the characteristics of the disease and the prolonged use of glucocorticoid hormone thera-py,may affect the bone formation and bone absorption of the patient,followed by severe successive osteo-porosis,thereby increasing the risk of osteoporotic vertebral fractures.Vertebral compression fractures of the spine are common fracture types in patients with osteoporotic fractures.Osteoporosis is a common complication after glucocorticoid therapy in patients with autoimmune diseases.Percutaneous vertebro-plasty(PVP)and percutaneous kyphoplasty(PKP)are minimally invasive operation and are commonly used surgical methods for the treatment of osteoporotic vertebral compression fractures.However,due to the operation of spinal puncture during the operation,there are serious surgical risks such as bone cement leakage,spinal epidural hemorrhage,subdural hemorrhage,and subarachnoid hemorrhage in both PVP and PKP.As a result,it is necessary to evaluate the patient's body before surgery carefully,especially in the case of blood coagulation.This article reports a case of autoimmune disease patient admitted to Peking University People's Hospital due to lumbar 4 vertebral compression fracture combined with Sj?gren's syn-drome.The patient's preoperative examination showed that the activated partial thromboplastin time(APTT)was significantly prolonged.After completing the APTT extended screening experiment and lu-pus anticoagulant factor testing,the multi-disciplinary team(MDT)of Peking University People's Hospi-tal jointly discussed the conclusion that the patient's test results were caused by an abnormal self-immuni-ty anti-copulant lupus(LAC).Based on the results of the laboratory examination,the patient was con-sidered to be diagnosed with combined antiphospholipid syndrome(APS).For such patients,compared with the patient's tendency to bleed,we should pay more attention to the risk of high blood clotting in the lower limbs of the patient,pulmonary clots and so on.With timely anti-coagulation treatment,the patient safely passed the peripheral period and was successfully discharged from the hospital.Therefore,for pa-tients with autoimmune diseases with prolonged APTT in the perioperative period,doctors need to careful-ly identify the actual cause and carry out targeted treatment in order to minimize the risk of surgical and perioperative complications and bring satisfactory treatment results to the patients.

Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.

ObjectiveTo investigate the structural and functional characteristics of gut microbiota in common traditional Chinese medicine （TCM） syndromes of irritable bowel syndrome with diarrhea （IBS-D）. MethodsIBS-D patients who visited the Hospital of Chengdu University of Traditional Chinese Medicine， and healthy participants from the Physical Examination Centre of the same hospital were recruited from 1st January 2020 to 31st March 2021.The IBS-D patients were classified into syndrome of liver constraint and spleen deficiency， and syndrome of spleen deficiency and dampness exuberance； together with the recruited healthy participants， there were liver-constraint group， dampness-exuberance group， and healthy group. General information， including age， gender and body mass index （BMI）， were collected， and Irritable Bowel Syndrome Symptom Severity Scale （IBS-SSS） as well as Irritable Bowel Syndrome Quality of Life Scale （IBS-QOL） scores were additionally collected from IBS-D patients. Fresh fecal samples were also collected and tested by macro-genome sequencing technology for abundance statistical display， PCoA， Anosim， LEfSe bioinformatic analysis of the annotated gut microbiota structure and function. ResultsThere was no statistically significant difference in the general information of the participants in the three groups （P＞0.05）； the difference in the IBS-SSS and IBS-QOL scores between liver-constraint group and dampness-exuberance group were not statistically significant （P＞0.05）. The study included 28 cases each in liver-constraint group， dampness-exuberance group， and healthy group. The number of specific genes to patients in liver-constraint group was 269 135， with 216 156 in dampness-exuberance group and 249 759 in healthy group， accounting of total 1 784 036 in the three groups. There were differences in the relative abundance distribution of the top ten species of gut microbiota among the three groups， with smaller differences at the phylum， class and order levels， and larger differences at the family， genus and species levels. There were differences in the relative abundance of structure and function of the gut microbiota among the three groups. Species PCoA and Anosim analyses at the species level showed significant differences in the composition of the microbiota among the three groups. Further LEfSe analyses showed that patients in liver-constraint group were screened for 14 dominant strains， of which Clostridium sp. CAG 217， Lachnospira pectinoschiza， Anaerotruncus sp. CAG 528， Paeniclostridium sordellii， Eubecterium sp. CAG 76， Bacillus cereus were affected to a greater extent in abundance differences； dampness-exuberance group screened 24 species of dominant bacteria， of which Roseburia inulinivorans， Eubacterium sp. CAG 251， Roseburia hominis， Unclassified Eubacterium rectale， Roseburia intestinalis， and Megamonas funiformis were affected to a greater extent in abundance differences； no dominant functional genes were screened for patients in liver-constraint group， and dampness-exuberance group was screened for flagellum assembly （ko02040）， porphyrin metabolism （ ko00860）， salmonella infection （ko05132）， and benzoic acid degradation （ko00362）. The differentially dominant functional genes in liver-constraint group and dampness-exuberance group may mainly focus on metabolism （including biodegradation and metabolism of exogenous substances， energy metabolism， lipid metabolism， etc.）. ConclusionIBS-D with syndrome of liver constraint and spleen deficiency is characterized by the enrichment of 14 gut microbiota， such as Clostridium sp. CAG 217， while IBS-D with syndrome of spleen deficiency and dampness exuberance is characterized by the enrichment of 24 gut microbiota， such as Roseburia inulinivorans， and 4 functional enrichments， such as flagellum assembly. Clostridium sp. CAG 217 and Roseburia inulinivorans are expected to be biomarkers for IBS-D patients in the two syndromes， respectively.

Objective: To investigate the use of e-cigarette and analyze its influencing factors among high school students in Wuhan City, so as to provide insights into developing control measures for adolescents. Methods: From September to November 2019, high school students in Wuhan City were selected by the multi-stage stratified cluster random sampling method, and basic information, e-cigarette use and second-hand smoke exposure were collected through questionnaire surveys. Proportions of e-cigarette current use and attempt to use were analyzed, and factors affecting the current use of e-cigarettes were identified using a multivariable logistic regression model. Results: Totally 5 700 questionnaires were allocated, and 5 602 valid questionnaires were recovered, with an effective rate of 98.28%. The respondents included 2 925 males (52.21%) and 2 677 females (47.79%); 4 033 high school students (71.99%) and 1 569 vocational high school students (28.01%). The proportion of attempt to use e-cigarettes was 9.23%, and the proportion of current e-cigarette use was 2.03%. Multivariable logistic regression analysis identified male (OR=2.112, 95%CI: 1.285-3.471), vocational high school (OR=1.967, 95%CI: 1.214-3.186), private high school (OR=9.684, 95%CI: 5.648-16.605), family second-hand smoke exposure (OR=3.064, 95%CI: 1.741-5.392), second-hand smoke exposure in public places (OR=4.402, 95%CI: 1.687-11.484) and having close friends who were smokers (OR=6.432, 95%CI: 3.219-12.852) as factors affecting current e-cigarette use among high school students. Conclusions The proportion of current e-cigarette use among high school students in Wuhan City was 2.03%. Male, vocational high school, private high school, second-hand smoke exposure and having close friends who were smokers may be promoting factors for e-cigarette use.