OBJECTIVE: To explore the application value of joint detection of serum neutrophil-to-lymphocyte ratio (NLR), prostate-specific antigen (PSA) and MMP26 in differentiating prostate cancer (PCa) from benign prostatic hyperplasia (BPH). METHODS: A total of 61 PCa patients (PCa group) and 63 BPH patients (BPH group) who were treated in The Affiliated Huaian Hospital of Xuzhou Medical University from May 2022 to May 2024 were retrospectively included. The relevant clinical data of all subjects were collected with the serum NLR, PSA and MMP26 levels being detected. Multivariate logistic regression analysis was used to analyze the influencing factors in differentiating PCa from BPH. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum NLR, PSA and MMP26 in differentiating PCa from BPH. RESULTS: The levels of TC and LDL-C in the PCa group were higher than those in the BPH group. And the level of HDL-C in the PCa group was lower than that in the BPH group (P<0.05). The serum levels of NLR, PSA and MMP26 in the PCa group were higher than those in the BPH group (P<0.05). The results of multivariate logistic regression analysis showed that NLR, PSA and MMP26 were risk factors for the diagnosis of PCa in patients (P<0.05). The ROC results showed that the area under the curve (AUC) of NLR, PSA MMP26 and joint diagnosis in the identification of PCa was 0.804, 0.800, 0.809 and 0.905, respectively. The comparison results of AUC showed that the joint diagnosis was superior to the single diagnosis (Z=2.262, 2.177, 2.002, P<0.05). CONCLUSION The joint detection of serum NLR, PSA and MMP26 has significant application value in the differentiation of PCa and BPH, which is expected to become an effective tool for early screening and diagnosis of PCa.
Humans ; Male ; Prostatic Hyperplasia/blood* ; Prostate-Specific Antigen/blood* ; Diagnosis, Differential ; Prostatic Neoplasms/blood* ; Retrospective Studies ; Neutrophils ; Lymphocytes ; ROC Curve ; Aged ; Middle Aged

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Intestinal organoids are constructed by crypts or stem cells from the intestine under the 3D support of the culture matrix. They contain all mature cells of the intestine, and have become a new and efficient platform for studying the mechanism of intestinal diseases. Compared with 2D cell culture, organoids can not only more effectively simulate the physiological structure and function of the intestine, but also better restore the true ecology of the intestine in different external environments. Therefore, it is more widely used in the study of pathogenesis of different intestinal diseases. This article reviewed the new progress of intestinal organoids culture, and the application and progress of intestinal organoids in the pathogenesis of inflammatory bowel diseases, colorectal cancer and celiac disease in recent years, and also discussed the application of intestinal organoids in drug research and development and screening.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

OBJECTIVE: To explore the effectiveness of manipulation treatment for lumbar disc herniation (LDH) based on the model of muscle and bone assessment. METHODS: From May 2022 to August 2023, using the methods single-center randomized controlled in Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 72 patients were treated with LDH and divided into muscle and bone assessment model manipulation group and the two step seven gimmick group according to the random number table method, the muscle and bone assessment model manipulation group fall off in 1 case, the two step seven gimmick group falls off in 2 cases. There were 35 cases in the muscle and bone assessment model manipulation group, including 12 males and 23 females;The age was 27 to 48 years old with an average of (37.77±7.63) years old. The course of disease was 35 to 180 days with an average of (83.68±69.01) days. The patients were treated with manual therapy under the guidance of muscle and bone assessment model, twice a week for 4 weeks. There were 34 cases in the two step seven gimmick group including 12 males and 22 females;The age was 26 to 49 years old with an average of (37.59±7.43) years old;The course of disease was 40 to 175 days with an average of (82.15±68.87) days. The patients were treated with two step seven gimmick method, 2 times a week, for 4 weeks. The visual analogue scale (VAS) and Oswestry disability index (Oswestry disability index, ODI) questionnaire, muscle tension and lumbar spine angle and the straight leg-raising activities were compared between two groups before and 4 weeks after treatment. RESULTS: The VAS of the muscle and bone assessment model manipulation group and the two step seven gimmick group(6.51±0.61) and (6.62±0.56) before treatment decreased to 2.40±0.81 and 3.18±0.78 after 4 weeks of treatment, respectively, and the muscle and bone assessment model manipulation group was significantly lower than the two step seven gimmick group (P<0.01). The ODI of the muscle and bone assessment model manipulation group and the two step seven gimmick group were (64.57±5.11) and (65.02±5.18) before treatment, decreased to (18.60±2.27) and (24.70±2.14) after 4 weeks of treatment, and the ODI of the muscle and bone assessment model manipulation group was significantly lower than that of the two step seven gimmick group (P<0.01). Before the treatment, side erector spinae, gluteus medius, and gastrocnemius muscle tension were (59.95±2.60), (62.59±2.51), (49.97±2.01) in the muscle and bone assessment model manipulation group and (60.39±3.84), (62.47±3.27), (49.55±1.27) in the two step seven gimmick group;After 4 weeks of treatment, the muscle tension of erector spinae, gluteus medius and gastrocnemius on the affected side were (56.58±2.71), (60.44±2.31) and (49.19±1.57) in the muscle and bone assessment model manipulation group, (58.28±3.79), (60.11±2.87), (48.55±0.90) in the two step seven gimmick group, the differences had statistical significance before and after treatment of two groups(P<0.01). The muscle and bone assessment model manipulation group was better than the two step seven gimmick group in improving the erector spinae muscle tension on the affected side (P<0.05), and there was no significant difference in the rest (P>0.05). Before the treatment, lumbar proneness, stretch, subject to lateral flexion and lateral angle of the straight leg-raising on the affected side were (46.00±8.89)°, (13.57±3.75)°, (12.29±3.50) °, (43.71±7.98) ° in the muscle and bone assessment model manipulation group, (45.14±6.24) °, (12.23±3.75) °, (12.66±2.98) ° and (44.18±3.50) ° in the two step seven gimmick group. After 4 weeks of treatment, the angles of lumbar flexion, extension, flexion on the affected side and straight leg raising on the affected side were (76.29±4.43) °, (20.00±1.71) °, (22.43±2.81) °, (70.41±7.59) ° in the muscle and bone assessment model manipulation group, and (75.75±6.38) °, (16.43±3.36) °, (20.19±3.52) °, (65.42±6.15) ° in the two step seven gimmick group. The difference had statistical significance before and after treatment in two groups(P<0.01), a comparison between groups, after 4 weeks of treatment, the angles of lumbar flexion and extension, affected side flexion, and lower limb straight leg elevation in the muscle and bone assessment model manipulation group were better than those in the two step seven gimmick group (P<0.05). Before the treatment, pelvic tilt, lumbar lordosis angle were (2.71±1.01) mm, (37.63±3.35) ° in the muscle and bone assessment model manipulation group, and (2.69±0.97) mm, (36.98±3.73) ° in the two step seven gimmick group;After 4 weeks of treatment, the pelvic tilt and lumbar lordosis angle were (0.84±0.36) mm and (41.64±2.96) ° in the muscle and bone assessment model manipulation group, and those in the method of two step seven gimmick group were (1.18±0.75) mm and (41.70±3.14) °. There were significant differences before and after treatment in both groups (P<0.01), and the improvement of pelvic tilt in the muscle and bone assessment model manipulation group was better than that in the method of two step seven gimmick group after 4 weeks of treatment (P<0.05). CONCLUSION The manipulation under the guidance of the muscle and bone assessment model can effectively improve the pain and dysfunction of LDH patients, and has a better effect than the two-step seven-method manipulation group in improving the muscle tension, lumbar motion function and posture.
Humans ; Male ; Female ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae

Humans ; Mutation, Missense ; KCNQ1 Potassium Channel/genetics* ; Long QT Syndrome/genetics* ; Phenotype ; Mutation ; Pedigree