ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Objective:To investigate the risk factors of hypoparathyroidism (HPT) and hypocalcemia in patients undergoing total thyroidectomy (TT), and to explore the changes of parathyroid hormone and blood calcium after TT.Methods:The clinical data of 101 patients undergoing TT from November 2018 to September 2022 in the First Hospital of Hebei Medical University were retrospectively analyzed. The basic clinical data were recorded. The blood calcium and parathyroid hormone levels were measured before surgery and 1 d, 1 week after surgery. The occurrence of postoperative hypocalcemia was recorded. According to postoperative parathyroid hormone level, the patients were divided into control group (normal parathyroid function) and HPT group (reduced parathyroid hormone level). The patients with postoperative hypocalcemia symptoms were classified as the hypocalcemia symptoms group, and the patients without postoperative hypocalcemia symptoms were classified as the non-hypocalcemia symptoms group. Multivariate Logistic regression was used to analyze the independent risk factors of HPT and hypocalcemia in TT patients.Results:The postoperative parathyroid hormone level decreased in 41 cases (HPT group) and normal in 60 cases (control group). There were 24 patients with postoperative hypocalcemia symptoms (hypocalcemia symptoms group) and 77 patients without postoperative hypocalcemia symptoms (non-hypocalcemia symptoms group). The rate of using bipolar electric coagulation forceps in HPT group was significantly lower than that in control group: 31.71% (13/41) vs. 76.67% (46/60), while the rate of central lymph node dissection was significantly higher than that in control group: 82.93% (34/41) vs. 60.00% (36/60), and there were statistical differences ( P<0.01 and <0.05). Multivariate Logistic regression analysis result showed that TT combined with unilateral or bilateral central lymph node dissection was an independent risk factor for HPT in TT patients ( OR = 1.706 and 1.501, 95% CI 1.019 to 2.856 and 1.052 to 2.140, P<0.05). The preoperative serum calcium, postoperative serum calcium and postoperative parathyroid hormone in hypocalcemia symptoms group were significantly lower than those in hypocalcemia symptoms group: (2.32 ± 0.11) mmol/L vs. (2.37 ± 0.11) mmol/L, (2.16 ± 0.21) mmol/L vs. (2.25 ± 0.18) mmol/L and 3.00 (1.00, 5.45) ng/L vs. 19.90 (8.50, 33.80) ng/L, and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that postoperative parathyroid hormone was an independent risk factor of hypocalcemia symptoms in TT patients ( OR = 0.927, 95% CI 0.883 to 0.974, P<0.01). In patients with HPT, the blood calcium at 1 week after surgery was significantly lower than that at 1 d after surgery: (2.07 ± 0.19) mmol/L vs. (2.17 ± 0.25) mmol/L, and there was statistical difference ( t = 2.05, P<0.05); the parathyroid hormone at 1 week after surgery was significantly higher than that at 1 d after surgery: 8.30 (3.55, 19.55) ng/L vs. 3.60 (1.00, 6.85) ng/L, and there was statistical difference ( Z = - 3.78, P<0.01). Conclusions:When performing TT, standardizing the surgical techniques, reducing unnecessary central lymph node dissection, and using bipolar electric coagulation forceps as much as possible can help to reduce the occurrence of postoperative HPT. The levels of postoperative parathyroid hormone and blood calcium should be promptly detected, the change of both should be given attention, and do a good job in preventing and treating hypocalcemia.

Objective Chronic atrophic gastritis(CAG)is often accompanied by intestinal flora disorder and intestinal symptoms,forming the phenomenon of"stomach disease involving intestine".This study explored the dynamic correlation between intestinal symptoms and qi-stagnation degree in patients with CAG qi-stagnation syndrome and analyzed the characteristics of gut microbiota from the perspective of"spleen-stomach system serving as the pivotal hub of qi movement"in TCM.Methods According to the syndrome element differentiation method,410 patients with CAG were divided into four groups:non-qi-stagnation group,mild qi-stagnation group,moderate qi-stagnation group and severe qi-stagnation group.Correlation analysis and 16S intestinal flora sequencing technology were used to analyze the correlation and differential flora between the degree of CAG qi-stagnation and intestinal symptoms.Results Patients with CAG qi-stagnation syndrome were often accompanied by intestinal symptoms such as frequent flatulence,poor defecation and alternating loose-constipated stools.The frequency of cases was significantly positively correlated with the degree of qi-stagnation"non-mild-moderate-severe"(P<0.05).There was a difference in the abundance of gut microbiota between the four groups of CAG qi-stagnation none,mild,moderate and severe.The relative abundance of Streptococcus,Subdoligranulum,Eubacterium_coprostanoligenes_group and Haemophilus was positively correlated with the degree of qi-stagnation.The relative abundance of Ruminococcus_torques_group and Butyricicoccus showed a negative correlation,and Haemophilus was statistically significant among the four groups(P<0.05).Conclusion This study can provide clinical evidence and micro-mechanism for the connotation of"gastrointestinal co-morbidities"and"different diseases with the same syndrome",which may open up new ideas for clinical diagnosis and treatment.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective:To investigate the risk factors of hypoparathyroidism (HPT) and hypocalcemia in patients undergoing total thyroidectomy (TT), and to explore the changes of parathyroid hormone and blood calcium after TT.Methods:The clinical data of 101 patients undergoing TT from November 2018 to September 2022 in the First Hospital of Hebei Medical University were retrospectively analyzed. The basic clinical data were recorded. The blood calcium and parathyroid hormone levels were measured before surgery and 1 d, 1 week after surgery. The occurrence of postoperative hypocalcemia was recorded. According to postoperative parathyroid hormone level, the patients were divided into control group (normal parathyroid function) and HPT group (reduced parathyroid hormone level). The patients with postoperative hypocalcemia symptoms were classified as the hypocalcemia symptoms group, and the patients without postoperative hypocalcemia symptoms were classified as the non-hypocalcemia symptoms group. Multivariate Logistic regression was used to analyze the independent risk factors of HPT and hypocalcemia in TT patients.Results:The postoperative parathyroid hormone level decreased in 41 cases (HPT group) and normal in 60 cases (control group). There were 24 patients with postoperative hypocalcemia symptoms (hypocalcemia symptoms group) and 77 patients without postoperative hypocalcemia symptoms (non-hypocalcemia symptoms group). The rate of using bipolar electric coagulation forceps in HPT group was significantly lower than that in control group: 31.71% (13/41) vs. 76.67% (46/60), while the rate of central lymph node dissection was significantly higher than that in control group: 82.93% (34/41) vs. 60.00% (36/60), and there were statistical differences ( P<0.01 and <0.05). Multivariate Logistic regression analysis result showed that TT combined with unilateral or bilateral central lymph node dissection was an independent risk factor for HPT in TT patients ( OR = 1.706 and 1.501, 95% CI 1.019 to 2.856 and 1.052 to 2.140, P<0.05). The preoperative serum calcium, postoperative serum calcium and postoperative parathyroid hormone in hypocalcemia symptoms group were significantly lower than those in hypocalcemia symptoms group: (2.32 ± 0.11) mmol/L vs. (2.37 ± 0.11) mmol/L, (2.16 ± 0.21) mmol/L vs. (2.25 ± 0.18) mmol/L and 3.00 (1.00, 5.45) ng/L vs. 19.90 (8.50, 33.80) ng/L, and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that postoperative parathyroid hormone was an independent risk factor of hypocalcemia symptoms in TT patients ( OR = 0.927, 95% CI 0.883 to 0.974, P<0.01). In patients with HPT, the blood calcium at 1 week after surgery was significantly lower than that at 1 d after surgery: (2.07 ± 0.19) mmol/L vs. (2.17 ± 0.25) mmol/L, and there was statistical difference ( t = 2.05, P<0.05); the parathyroid hormone at 1 week after surgery was significantly higher than that at 1 d after surgery: 8.30 (3.55, 19.55) ng/L vs. 3.60 (1.00, 6.85) ng/L, and there was statistical difference ( Z = - 3.78, P<0.01). Conclusions:When performing TT, standardizing the surgical techniques, reducing unnecessary central lymph node dissection, and using bipolar electric coagulation forceps as much as possible can help to reduce the occurrence of postoperative HPT. The levels of postoperative parathyroid hormone and blood calcium should be promptly detected, the change of both should be given attention, and do a good job in preventing and treating hypocalcemia.

Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

Objective:To evaluate the preventive effects of transcutaneous electrical acupoint stimulation (TEAS) on chronic pain after lumbar spine surgery.Methods:This was a secondary analysis conducted on the studies assessing the effect of TEAS on gastrointestinal function in patients undergoing lumbar spinal surgery. Fifty lumbar spinal stenosis patients of either sex, aged 50-75 yr, with a body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status cassification Ⅰ or Ⅱ, with expected operation time≥3 h, undergoing lumbar spinal surgery under general anesthesia, were enrolled and assigned into 2 groups ( n=25 each) using a random number table method: control group (C group) and TEAS group. In group C, stimulating electrodes were placed at the non-acupoint parts of the limbs, but no electrical stimulation was applied. In group TEAS, the bilateral Neiguan (PC6), Hegu (L14), Zusanli (ST36), Shangjuxu (ST37) and Xiajuxu (ST39) were stimulated with disperse-dense waves at a frequency of 2/100 Hz. The intensity of stimulation was the maximum current that patients could tolerate. The intervention was performed once a day for 30 min per session at 30 min prior to anesthesia induction and on postoperative days 1-7. Telephone follow-ups were conducted at 3, 6 and 12 months after surgery to record the occurrence of postoperative moderate-to-severe lower back pain and leg pain (Numerical Rating Scale score ≥4), and the Oswestry Disability Index (ODI) value and four-item neuropathic pain questionnaire scores. The pain-related medical visits and usage of nonsteroidal anti-inflammatory drugs were also recorded after surgery. Results:Three patients in each group were lost to follow-up. Compared with group C, the incidence of chronic low back pain was significantly decreased at 6-12 months after surgery, the ODI value and four-item neuropathic pain questionnaire scores were decreased at 12 months after surgery ( P<0.05), ODI value difference reached the minimal clinically important difference, the proportion of patients requiring medical visits due to postoperative pain and usage rate of nonsteroidal anti-inflammatory drugs were decreased at 6-12 months after surgery ( P<0.05), and no significant change in the incidence of chronic moderate-to-severe leg pain was found at each time period after surgery in group TEAS( P>0.05). Conclusions:TEAS can prevent the occurrence of chronic lower back pain and improve functional impairment in patients undergoing lumbar spine surgery.

Objective To construct a nomogram prediction model for predicting hemoglobin A1c(HbA1c)failure in type 2 diabetes mellitus(T2DM)patients.Methods A total of 936 inpatients with T2DM admitted to the Department of Endocrinology of the Affiliated Hospital of Shandong Second Medical University from January 2021 to January 2022 were selected as the research objects and divided into the non-standard group(HbA1c≥7%,n=801)and the standard group(HbA1c<7%,n=135).Univariate analysis was used to screen the related factors of HbA1c failure.Logistic regression multivariate model was used to analyze the influencing factors of HbA1c failure in T2DM patients.The R language was used to construct a nomogram,and the area under the receiver operating characteristic(ROC)curve(AUC)was used to evaluate the predictive ability of the model.The C-index and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model.Results There were statistically significant differences in triglyceride(TG),low-density lipoprotein cholesterol,direct bilirubin,urinary albumin/creatinine ratio(UACR),self-monitoring of blood glucose(SMBG),meat and vegetable pairing,hot pot,whole grain and animal viscera consumption between the two groups(P<0.05).Logistic regression analysis showed that TG(OR 1.699,95%CI 1.298～2.222),UACR(OR 1.003,95%CI 1.001～1.005),SMGB(OR 0.480,95%CI 0.313～0.735),more meat and less vegetables(OR 1.432,95%CI 1.062～1.931)were the influencing factors of HbA1c failure.The AUC of the nomogram prediction model based on the influencing factors was 0.711,with C-index 0.710(95%CI 0.663～0.758)and good calibration(χ2=11.185,P=0.191).Conclusions The nomogram prediction model for HbA1c failure in T2DM patients established based on TG,UACR,SMGB,meat and vegetarian mix has good discrimination and calibration,which can provide certain reference value for warning of poor blood glucose control.

Polygonatum sibiricum， as a traditional Chinese medicine with both medicinal and edible properties， has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs， tonifying the spleen and benefiting Qi， and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system， effectively enhancing and improving the morphology and function of immune organs， stimulating the proliferation and activation of immune cells， and regulating the secretion and release of immune factors， thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum， there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore， this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years， and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects： including increasing the organ index of the spleen and thymus， increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells， improving intestinal flora imbalance， regulating the quantity and proportion of T lymphocyte subsets， increasing the level of immunoglobulin， promoting the proliferation of macrophages， enhancing the activity of natural killer cells， increasing the number of white blood cells， and promoting the maturation of dendritic cells， providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum， and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.