BACKGROUND:Lumbar fixed-point rotation operation needs collaborative operation of the doctor's hands,and outputs rotation and thumb thrust.Lumbar disc herniation can be treated through disc displacement and adjusting stress distribution.However,the mechanical effects of thumb thrust and the biomechanical effects of loading direction on manipulative effects remain unclear. OBJECTIVE:To compare the biomechanical difference of lumbar fixed-point rotation manipulation for treating lumbar disc herniation under different thrust directions. METHODS:The L3-5 normal three-dimensional finite element model was constructed and validity was verified.According to the intervertebral disc degeneration Pfirrmann grade,intervertebral disc degeneration was simulated by modifying the L4/5 intervertebral space height,the volume of the nucleus pulposus,as well as the material parameters of the annulus fibrosus,nucleus pulposus,and ligament.Finally,the pathological model of L4/5 moderate disc degeneration with left para-central herniation was constructed,and then the pathological models were used as research objects.Simulation technique:spinning to the right;taking the condition on changing the direction of the thumb thrust to establish three modes of operation(M1:thumb push to the left;M2:thumb push to the right;M3:no thrust push).The protrusion displacement and the disc stress,and the stress and strain of the facet joint cartilage were compared in the three operating modes. RESULTS AND CONCLUSION:(1)Maximum displacement value of L4/5 disc herniation:displacement was 2.672 3 mm for M1,1.156 1 mm for M2,1.826 4 mm for M3,M1＞M3＞M2.(2)The maximum Von Mises stress of L4/5 discs was 1.846 7 MPa for M1,0.419 0 MPa for M2,and 1.257 9 MPa for M3,M1＞M3＞M2.(3)L4/5 bilateral small cartilage produced different degrees of contact stress changes:It was 0.485 5 MPa for M1,0.026 7 MPa for M2,and 0.441 4 MPa for M3,M1＞M3＞M2.Right cartilage contact force was 0.000 5 MPa for M1,0.025 9 MPa for M2,and 0.001 3 MPa for M3,M2＞M3＞M1;the left greater than the right,M1 had the highest value;cartilage strain was consistent with contact stress changes.(4)Different operation modes will have some biomechanical influences on the diseased intervertebral disc and accessory structure.The M1 operation mode can maximize the displacement of protrusion,disc stress and left joint cartilage contact,which can better promote disc displacement,balance stress distribution and reduce facet joint disorder,so the operation is better.

BACKGROUND:It has been shown that in a mouse model of acute traumatic brain injury,the transcriptional and translational levels of silent information regulator 1(SIRT1)activated by drugs significantly elevates the expression of SIRT1 in brain tissue,reduces inflammatory and oxidative stress in brain tissue,and improves neurological function. OBJECTIVE:To investigate the mechanism of intraperitoneal injection of SRT1720,an activator of SIRT1,to alleviate acute traumatic brain injury in rats. METHODS:Ninety Sprague-Dawley rats were randomized into three groups(n=30 per group):a sham group(without modeling),a model group and an activator group.Animal models of acute traumatic brain injury were established in the latter two groups.At 6 hours after modeling,the sham,model and activator groups were injected intraperitoneally with dimethyl sulfoxide solution,methylsulfoxide solution and SRT1720 once a day for 28 days,respectively.The time points for sampling were set,and rats'neurological function,brain tissue water content,brain tissue oxidative stress and inflammatory response,brain tissue morphology,apoptosis and angiogenesis,and the protein expression of SIRT1 in brain tissue were detected and measured. RESULTS AND CONCLUSION:Compared with the sham group,the modified neurological deficit score,brain tissue water content and apoptosis rate of rats were increased in the model group at 7,14 and 28 days of injection(P<0.05);compared with the model group,the modified neurological deficit score,brain tissue water content and apoptosis rate of rats were decreased in the activator group(P<0.05).Compared with the sham group,the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were increased(P<0.05),the levels of malondialdehyde,tumor necrosis factor α and interleukin 6 in the serum were increased(P<0.05),and the levels of superoxide dismutase in the serum were decreased in the model group at 7,14 and 28 days of injection(P<0.05).Compared with the model group,the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were decreased(P<0.05),the levels of malondialdehyde,tumor necrosis factor α and interleukin 6 in the serum were decreased(P<0.05),and the levels of superoxide dismutase in the serum were increased in the activator group at 7,14 and 28 days of injection(P<0.05).Immunohistochemical staining at 7,14 and 28 days of injection showed that the number of new vessels in the brain tissue was higher in the model group than the sham group(P<0.05)as well as higher in the activator group than the model group(P<0.05).Western blot assay indicated that at 7,14 and 28 days of injection,the expression of SIRT1 protein in the brain tissue was lower in the model group than the sham group(P<0.05)and higher in the activator group than the model group(P<0.05).Hematoxylin-eosin staining showed that at 7,14 and 28 days of injection,the degree of brain injury in the activator group was less than that in the model group.To conclude,intraperitoneal injection of the SIRT1 signal activator SRT1720 can significantly reduce oxidative and inflammatory stress in the brain tissue,inhibit neuronal apoptosis,promote angiogenesis,and alleviate brain injury in rats with acute traumatic brain injury.

Objective To evaluate the outcome indicators in clinical research on TCM treatment for polycystic ovary syndrome(PCOS);To provide a theoretical basis for establishing the PCOS clinical core outcome indicator set.Methods Relevant clinical research about TCM treatment for PCOS was retrieved from CNKI,Wanfang Data,VIP,CBM,Embase,PubMed,Web of Science and Cochrane Library from 1st,Jan.2019 to 15th,Nov.2023.Research articles were screened based on predefined inclusion and exclusion criteria,and a comprehensive analysis was conducted on the extracted data.Results A total of 951 clinical studies were included(915 in Chinese and 36 in English),involving 86 369 patients,with 221 outcome indicators identified,and a total frequency of 8 991 occurrences.Analysis revealed that commonly used outcome indicators included hormone levels(such as luteinizing hormone,follicle-stimulating hormone,testosterone),overall efficacy rate,ovulation rate,pregnancy rate,TCM syndrome score,ovarian volume and insulin resistance index.However,there was considerable variation in the choice of indicators across different studies,and some indicators were misaligned with clinical needs,lacking a focus on long-term prognosis and safety.Conclusion Clinical research on TCM treatments for PCOS often demonstrates significant variability in outcome indicators,lack of clarity between primary and secondary indicators,disorganized description of indicators,diversity in the choice of measurement tools,and a lack of indicators for specific populations.These problems lead to difficulties in combining similar studies for meta-analysis and fail to provide high-level evidence-based clinical guidance.There is an urgent need to establish a core set of outcome indicators for clinical research on TCM treatment for PCOS.

Objective: To construct nomogram to predict the risk of bone metastasis in patients with non-small cell lung cancer(NSCLC). Methods: The clinical data of NSCLC patients diagnosed in the hospital were retrospectively analyzed, including the occurrence of bone metastasis, age, gender, pathological type, smoking status, PS score, TN stage, metastasis of other sites before bone metastasis, carcinoembryonic antigen(CEA) level, alpha fetoprotein(AFP) level, serum calcium(Ca2+), serum phosphorus(P), alkaline phosphatase(ALP) level, which were determined by univariate and multivariate logistic regression analysis. Receiver operating characteristic curve(ROC) and decision curve analysis were used, DCA was used to verify the accuracy and clinical benefit of the model, and nomogram was used to visualize the model. Results: Area under the ROC curve(AUC) showed that in the modeling group(n=138) and the validation group(n=92), the AUC value predicted by combined indicators(age, gender, pathological type, CEA, ALP)(modeling group=0.792, validation group=0.629) was higher than that predicted by single indicator. Conclusion The prediction model constructed in this study has good effect and can provide reference for clinical screening of high-risk patients with bone metastasis of NSCLC.

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

Objective:To explore the clinical effect of the fractional carbon dioxide laser in the treatment of contracture scars.Methods:A retrospective before-after self-control study was conducted. From December 2016 to April 2021, 16 patients (7 males and 9 females, aged 3-49 years) with contracture scars causing impaired function of the adjacent joint were admitted to Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Eighteen joint scars of 16 patients were treated with fractional carbon dioxide laser every 2-3 months until the joint retained its normal range of motion or the effect plateaued. The treatment times of each patient were recorded. Before the first treatment and 6 months after the last treatment, the ranges of motion of the affected joint were measured in each patient, and the difference was calculated, meanwhile, the Vancouver Scar Scale (VSS) was used to evaluate the scar of each patient. In the treatment of 1 joint scar in each of 6 patients (totally 6 times of treatments), the ranges of motion of the affected joint before the current treatment, immediately after the treatment, and at the first follow-up after the treatment were documented, and the differences between the ranges before and immediately after the treatment as well as between the ranges before and at the first follow-up after the treatment were calculated. Adverse effects after the treatment in the treatment area were documented. At the last follow-up, a self-made questionnaire was used to collect the implementation status of the physical therapy and other scar management modalities during the treatment interval and follow-up period. Data were statistically analyzed with Wilcoxon rank sum test.Results:Eighteen joint scars in 16 patients received 2 (1, 3) times of fractional carbon dioxide laser treatment. The range of motion of the affected joint of 16 patients 6 months after the last treatment was 56.5 (39.0, 128.8)°, notably higher than 38.4 (22.9, 116.3)° before the first treatment ( Z=-3.724, P<0.01), showing a remarkable improvement by 17.4 (8.0, 24.1)°. The vascular distribution, softness, and thickness scores, and total score in VSS scoring of scars of 16 patients 6 months after the last treatment were significantly lower than those before the first treatment ( Z=-2.989, -3.762, -2.814, -3.739, P<0.01), with the most obvious improvement in softness. In 6 times of treatments, the range of motion of the affected joint immediately after treatment and at the first follow-up of (2.5±0.6) months after treatment were 156.2 (148.0, 164.2)° and 160.2 (156.7, 166.4)°, both notably higher than 151.4 (145.7, 155.3)° before treatment ( Z=-2.201, -2.201, P<0.05), showing a remarkable improvement by 9.1 (4.4, 13.0)° and 13.1 (8.0, 15.7)°, respectively. No adverse effects such as blisters, infection, or hypertrophic scar formation were observed in the treatment area of 16 patients after treatment. Most patients adopted physical therapy, compression, silicone gel or sheets, and braces during the treatment interval and follow-up period. Conclusions:The fractional carbon dioxide laser can soften the scar and increase the range of motion of the affected joint, which is suitable for the clinical treatment of mild contracture scars.

Objective: To study the effects of resistant dextrin (RD) on liver fat deposition in high-fat diet-fed (HFD) mice, and to further explore whether it can regulate the AMPK signaling pathway. Methods: Thirty-six 4-week-old male C57BL/6 mice were randomly divided into three groups: normal control group (chow), high-fat diet group (HFD), and high-fat diet+ resistant dextrin group (HFD+ RD, 10 g·kg^-1·d^-1). After 12 weeks of intervention, the liver tissues and serum samples were collected. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), aspartate aminotransferase (AST), alanine transaminase (ALT) levels and liver TG were measured. Liver tissue HE and oil red O staining were performed to observe hepatocyte steatosis and liver fat deposition. Quantitative real-time PCR was performed to detect the relative expression of fatty acid synthesis related genes SREBP1, ACC, SCD1 in the liver tissue, and Western blot was performed to detect relative protein levels of pAMPK, SREBP1, Fasn, and ACC in the liver. Results: Compared with chow group, the body weight gain, fasting blood glucose (FBG), serum TC, LDL-C, HDL-C, and ALT levels were increased in HFD group (P<0.01), and serum AST level was also increased (P<0.05). Moreover, liver oil red O staining revealed that liver fat deposition was much more obvious in HFD group than that in chow group, and liver TG was also increased in HFD group (P<0.01). The mRNA levels of SREBP1 and ACC were increased in HFD group compared with that in chow group, and the protein level of pAMPK was reduced in HFD group (P<0.05). As compared with HFD group, the body weight gain, serum TG, TC, LDL-C, HDL-C and ALT levels were significantly reduced in RD group (P<0.01), and FBG level was also reduced (P<0.05). Moreover, RD treatment alleviated liver fat deposition and TG accumulation (P<0.01). The mRNA levels of SREBP1, ACC, and SCD1 were all reduced in RD group compared with HFD group. The protein level of pAMPK was increased, and the expression of Fasn was reduced with RD treatment (P<0.01). Conclusion Resistant dextrin improves liver fat deposition and activates the AMPK signaling pathway in HFD-fed mice.

[Abstract] Objective: To explore the key genes and molecular mechanisms of liver metastasis in colorectal cancer (CRC), and to provide potential targets and biomarkers for the treatment of CRC with liver metastasis. Methods: Based on the bioinformatics method, the gene data sets of CRC liver metastasis were downloaded from the GEO database to screen the differentially expressed genes (DEGs); the GO and KEGG enrichment analyses of DEGs were performed by using DAVID online tool, and the protein-protein interaction (PPI) network was constructed to screen out the key genes, and subsequently the prognosis was analyzed. Results: A total of 321 DEGs were selected from 183 CRC specimens and 39 liver metastasis specimens, including 153 up-regulated genes and 168 downregulated genes. The results of enrichment analysis of GO and KEGG showed that the functions of DEGs were mainly related to protein activation cascade, inflammatory response, extracellular matrix, platelet degranulation, complement and coagulation cascade reaction etc. 8 key CRC genes (ALB, APOB, FGA, F2, APOA1, SERPINC1, FGG and AHSG) were screened by PPI network. Survival analysis showed that patients with high expressions of SERPINC1 and FGG had poor prognosis(all P<0.05). Conclusion: The biological functions and signaling pathways of DEGs are related to the occurrence and development of liver metastasis. The 8 key genes may be the potential therapeutic targets of CRC liver metastasis, and SERPINC1 and FGG may be new prognostic markers.

Lung cancer is the leading cause of cancer death and non-small cell lung cancer (NSCLC) accounts for >85% of all cancer deaths. Although chemotherapy and targeted therapy have improved clinical outcomes, prognosis remains poor. With the development of immunotherapy, the treatment strategy for patients with NSCLC has changed. Nivolumab, a human immunoglobulin G4 monoclonal antibody, was the first programmed cell death protein-1 (PD-1) inhibitor drug to be approved for treating advanced NSCLC and has become the primary drug for treating advanced NSCLC. However, there remains a lack of clinical biomarkers to predict the efficacy of nivolumab. In this review, we discuss the progress of therapeutic mechanisms, pharmacokinetics, pharmacology, clinical trials of monotherapy and combined therapy, adverse events, and predictive biomarkers.

Objective:Dipeptidyl peptidase 4 (DPP4) is an incretin lyase, while DPP4 inhibitors have been used clinically as hypoglycemic drugs. Serum DPP4 is related to metabolic diseases such as cardiovascular disease and obesity, and lipid metabolic disorder is an important part of metabolic syndrome. This study was designed to explore the relationship between DPP4 and lipid metabolic disorder.Methods:There were 3644 participants from Chengqiao Town, Chongming District, Shanghai. All of the subjects recruited were residents between 40-70 years old, who have not diagnosed as diabetes mellitus (DM) and who have never used any lipid-lowering drugs. Glucose, insulin, lipid level, DPP4 activity and liver enzymes in serum of all participants were tested. In addition, height, weight and blood pressure were also recorded.Results:Participants were divided into four groups (Q1-Q4) according to the quartile value of serum DPP4 activities. Along with the increase of serum DPP4 activity, triglyceride, total cholesterol, and blood glucose levels increased, and triglyceride increased from (1.23 ± 0.70) mmol/L to (2.31 ± 1.89) mmol/L. Compared with cholesterol levels, the triglyceride was more closely related to DPP4 activity [the correlation coefficients of triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) were 0.424, 0.281, 0.142, and 0.027, respectively]. After adjusting for confounding factors (age, gender, BMI), the result was similar. With the increase of DPP4 enzyme activity, the Q4 group had a higher risk of developing hyperglyceridemia ( OR=5.25) than the Q1 group, and the result was almost unchanged after adjusting for confounding factors and blood glucose levels ( OR=4.90). Conclusion:Serum DPP4 activity is independently related to blood lipid levels, and is particularly closely related to blood TG levels.