[摘 要] 目的：探讨绿茶单体表没食子儿茶素没食子酸酯（EGCG）对大鼠肝癌发生过程中肠道菌群结构变化的影响。方法：建立二乙基亚硝胺（DEN）诱导的肝癌大鼠模型。将26只SD大鼠随机分成3组，分别为正常对照组、肝癌组和EGCG干预组。从实验开始第1天起，EGCG干预组每日给予EGCG（40 mg/kg）灌胃，正常对照组和肝癌组给予等量生理盐水灌胃，1次/日，持续至第20周。灌胃结束后，采集大鼠粪便样本，提取DNA，进行高通量16S rRNA V3-V4区测序；处死大鼠，取肝，观察肿瘤形成情况，并计算肝癌发生率。对测序数据进行生物信息学分析：经质控、聚类获得操作分类单元（OTU）表，据此计算α多样性指数（包括Observed species、Chao1、Shannon和Simpson指数），并进行β多样性分析。同时，对物种进行分类学注释，比较各组间菌群组成与丰度差异。结果： EGCG干预组大鼠（8只）肝脏肿瘤形成率明显低于肝癌组（10只）（50% vs 100%， P = 0.023），正常对照组（8只）大鼠无肿瘤发生。在肠道菌群方面，肝癌组操作分类单元（OTU）数量远低于正常对照组（P <0.001），而EGCG干预组OTU数量总体上高于肝癌组（P = 0.021）。α多样性分析显示，肝癌组Shannon指数低于正常对照组（P < 0.05）；此外，与肝癌组相比，EGCG干预组的Observed species指数、Chao1指数、Shannon指数和Simpson指数均显著提高（P < 0.05）。β多样性分析及主坐标分析（PCoA）表明，三组肠道菌群结构存在显著分离（PERMANOVA， R² = 0.3918， P = 0.001），其中EGCG干预组群落结构介于肝癌组与正常对照组之间，并更接近于正常对照组。肝癌组大鼠较正常大鼠肠道菌群中链球菌等潜在致病菌富集，丁酸产生相关菌（如丁酸球菌属、瘤胃球菌属等）丰度显著降低（P < 0.05）。相比之下，在EGCG干预肝癌发生过程中，大鼠肠道菌群结构相对稳定。厚壁菌门/拟杆菌门比值较肝癌组显著提高（P < 0.05），益生菌（如双歧杆菌属、乳杆菌属等）和丁酸产生相关菌（如丁酸球菌属）富集。结论：EGCG干预可降低DEN诱导的大鼠肝癌发生率，并有助于稳定肠道菌群结构，其作用可能与增加菌群多样性、促进益生菌及丁酸产生菌富集、恢复菌群平衡有关。

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

Objective:To explore the correlation between smoking behavior of employees in heavy industry enterprises and risk factors for cardiovascular and cerebrovascular diseases.Methods:A cross-sectional study design was adopted. A questionnaire survey and physical examination data collection were conducted on employees of a heavy industry enterprise in Shaanxi Province using a cluster sampling method from March to April 2024. A total of 2 209 cases met the inclusion criteria. According to the smoking index (SI), participants were divided into a non-smoking group (SI=0, 1 316 cases), a low smoking group (SI400, 656 cases), and a high smoking group (SI≥400, 237 cases). According to the fagerstrom test for nicotine dependence (FTND) score, participants were divided into a non-dependence group (FTND=0, 1 316 cases), a mild dependence group (FTND=1-3, 623 cases), a moderate dependence group (FTND=4-6, 204 cases), and a severe dependence group (FTND≥7, 66 cases). Spearman rank correlation, univariate, and multivariate logistic regression analyses were used to compare differences in blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, homocysteine, and body mass index among the groups.Results:As the SI and FTND scores increased, blood pressure, low-density lipoprotein cholesterol, triglycerides, uric acid, and homocysteine all showed an increasing trend, while high-density lipoprotein cholesterol showed a decreasing trend (all P0.05). The systolic blood pressure, diastolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol (LDL-C), triglycerides, serum uric acid, and homocysteine in the high smoking group were higher than those in the non-smoking group [(124.93±16.55) vs (122.32±16.62) mmHg (1 mmHg=0.133 kPa), (80.86±11.10) vs (76.18±11.63) mmHg, 5.58 vs 5.29 mmol/L, (3.13±0.65) vs (2.95±0.56) mmol/L, 1.70 vs 1.09 mmol/L, (336.80±69.94) vs (299.00±86.43) μmol/L, 14.20 vs 11.76 μmol/L, all P0.001], the high-smoking group had lower HDL cholesterol than the non-smoking group [(1.34±0.30) vs (1.39±0.27) mmol/L, P0.001], the systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, triglycerides, serum uric acid, and homocysteine in the severely dependent group were higher than those in the non-dependent group [(132.09±16.69 )vs (122.32±16.62) mmHg, (81.32±12.97) vs (76.18±11.63) mmHg, 5.61 vs 5.29 mmol/L, (4.98±0.91 )vs (4.70±0.88) mmol/L, (3.19±0.62) vs (2.95±0.56) mmol/L, 1.87 vs 1.09 mmol/L, (328.95±75.21) vs (299.03±86.43) μmol/L, 14.38 vs 11.76 μmol/L, all P0.05], and the high density lipoprotein cholesterol (HDL-C) in the severely dependent group was lower than that in the non-dependent group [(1.32±0.30) vs (1.39±0.27) mmol/L, P0.001]. Multivariate analysis showed that SI and degree of tobacco dependence (DTD), were significantly correlated with fasting blood glucose, triglycerides, and LDL cholesterol, but the effect size of SI was too small ( OR=1.001, 95% CI: 1.000-1.001, P=0.002, OR=1.001, 95% CI: 1.001-1.002, P0.001, OR=1.001, 95% CI: 1.000-1.001, P=0.032). Conclusions:Smoking behavior among employees in heavy industry enterprises is significantly correlated with risk factors for cardiovascular and cerebrovascular diseases. The degree of tobacco dependence is closely related to the risk of abnormal fasting blood glucose, low-density lipoprotein cholesterol, and triglycerides.

Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.

Objective To observe the effects of Huoxue Tongjiang Decoction on the expressions of gelsolin(GSN),prosaposin(PSAP)and nuclear factor(NF)-κB in reflux esophagitis(RE)model rats;To explore its mechanism of protecting esophageal mucosa.Methods Totally 75 Wistar rats were randomly divided into control group,model group,Western medicine group,TCM low-and high-dosage groups,with 15 rats in each group.The control group was given celiac switch operation,the other groups were given modified partial cardiac myotomy and external pyloric partial ligation to prepare RE rat model.Seven days after operation,each group was given normal saline,Western medicine or corresponding dosage of Huoxue Tongjiang Decoction for gavage,twice a day for 14 days.HE staining was used to observe the morphology of esophageal mucosa and pathological score was evaluated,immunohistochemical staining was used to detect the positive expressions of GSN and PSAP in esophageal mucosa,and Western blot was used to detect the protein expressions of NF-κBp65 and p-NF-κBp65 in esophageal tissue,ELISA was used to detect the contents of serum tumor necrosis factor(TNF)-α and interleukin(IL)-6.Results Compared with the control group,the esophageal mucosa of the model group was obviously damaged,the pathological score increased,the expression of GSN in esophageal mucosa decreased,the expressions of PSAP,NF-κBp65 and p-NF-κBp65 protein increased,and the contents of TNF-α and IL-6 in serum increased,with statistical significance(P<0.01).Compared with the model group,the esophageal mucosal injury improved obviously in the Western medicine group and TCM low-and high-dosage groups,the pathological score decreased,the expression of GSN in esophageal mucosa increased,the expressions of PSAP,NF-κBp65 and p-NF-κBp65 protein decreased,and the contents of TNF-α and IL-6 in serum decreased,with statistical significance(P<0.05,P<0.01).Conclusion Huoxue Tongjiang Decoction can effectively improve the immune inflammation of esophageal mucosa in RE model rats,its mechanism may be related to regulating GSN,PSAP and NF-κB pathway and reducing the release of inflammatory factors TNF-α and IL-6.

Objective To observe the effects of Huoxue Tongjiang Decoction on the expressions of gelsolin(GSN),prosaposin(PSAP)and nuclear factor(NF)-κB in reflux esophagitis(RE)model rats;To explore its mechanism of protecting esophageal mucosa.Methods Totally 75 Wistar rats were randomly divided into control group,model group,Western medicine group,TCM low-and high-dosage groups,with 15 rats in each group.The control group was given celiac switch operation,the other groups were given modified partial cardiac myotomy and external pyloric partial ligation to prepare RE rat model.Seven days after operation,each group was given normal saline,Western medicine or corresponding dosage of Huoxue Tongjiang Decoction for gavage,twice a day for 14 days.HE staining was used to observe the morphology of esophageal mucosa and pathological score was evaluated,immunohistochemical staining was used to detect the positive expressions of GSN and PSAP in esophageal mucosa,and Western blot was used to detect the protein expressions of NF-κBp65 and p-NF-κBp65 in esophageal tissue,ELISA was used to detect the contents of serum tumor necrosis factor(TNF)-α and interleukin(IL)-6.Results Compared with the control group,the esophageal mucosa of the model group was obviously damaged,the pathological score increased,the expression of GSN in esophageal mucosa decreased,the expressions of PSAP,NF-κBp65 and p-NF-κBp65 protein increased,and the contents of TNF-α and IL-6 in serum increased,with statistical significance(P<0.01).Compared with the model group,the esophageal mucosal injury improved obviously in the Western medicine group and TCM low-and high-dosage groups,the pathological score decreased,the expression of GSN in esophageal mucosa increased,the expressions of PSAP,NF-κBp65 and p-NF-κBp65 protein decreased,and the contents of TNF-α and IL-6 in serum decreased,with statistical significance(P<0.05,P<0.01).Conclusion Huoxue Tongjiang Decoction can effectively improve the immune inflammation of esophageal mucosa in RE model rats,its mechanism may be related to regulating GSN,PSAP and NF-κB pathway and reducing the release of inflammatory factors TNF-α and IL-6.

Objective:To explore the correlation between smoking behavior of employees in heavy industry enterprises and risk factors for cardiovascular and cerebrovascular diseases.Methods:A cross-sectional study design was adopted. A questionnaire survey and physical examination data collection were conducted on employees of a heavy industry enterprise in Shaanxi Province using a cluster sampling method from March to April 2024. A total of 2 209 cases met the inclusion criteria. According to the smoking index (SI), participants were divided into a non-smoking group (SI=0, 1 316 cases), a low smoking group (SI400, 656 cases), and a high smoking group (SI≥400, 237 cases). According to the fagerstrom test for nicotine dependence (FTND) score, participants were divided into a non-dependence group (FTND=0, 1 316 cases), a mild dependence group (FTND=1-3, 623 cases), a moderate dependence group (FTND=4-6, 204 cases), and a severe dependence group (FTND≥7, 66 cases). Spearman rank correlation, univariate, and multivariate logistic regression analyses were used to compare differences in blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, homocysteine, and body mass index among the groups.Results:As the SI and FTND scores increased, blood pressure, low-density lipoprotein cholesterol, triglycerides, uric acid, and homocysteine all showed an increasing trend, while high-density lipoprotein cholesterol showed a decreasing trend (all P0.05). The systolic blood pressure, diastolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol (LDL-C), triglycerides, serum uric acid, and homocysteine in the high smoking group were higher than those in the non-smoking group [(124.93±16.55) vs (122.32±16.62) mmHg (1 mmHg=0.133 kPa), (80.86±11.10) vs (76.18±11.63) mmHg, 5.58 vs 5.29 mmol/L, (3.13±0.65) vs (2.95±0.56) mmol/L, 1.70 vs 1.09 mmol/L, (336.80±69.94) vs (299.00±86.43) μmol/L, 14.20 vs 11.76 μmol/L, all P0.001], the high-smoking group had lower HDL cholesterol than the non-smoking group [(1.34±0.30) vs (1.39±0.27) mmol/L, P0.001], the systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, triglycerides, serum uric acid, and homocysteine in the severely dependent group were higher than those in the non-dependent group [(132.09±16.69 )vs (122.32±16.62) mmHg, (81.32±12.97) vs (76.18±11.63) mmHg, 5.61 vs 5.29 mmol/L, (4.98±0.91 )vs (4.70±0.88) mmol/L, (3.19±0.62) vs (2.95±0.56) mmol/L, 1.87 vs 1.09 mmol/L, (328.95±75.21) vs (299.03±86.43) μmol/L, 14.38 vs 11.76 μmol/L, all P0.05], and the high density lipoprotein cholesterol (HDL-C) in the severely dependent group was lower than that in the non-dependent group [(1.32±0.30) vs (1.39±0.27) mmol/L, P0.001]. Multivariate analysis showed that SI and degree of tobacco dependence (DTD), were significantly correlated with fasting blood glucose, triglycerides, and LDL cholesterol, but the effect size of SI was too small ( OR=1.001, 95% CI: 1.000-1.001, P=0.002, OR=1.001, 95% CI: 1.001-1.002, P0.001, OR=1.001, 95% CI: 1.000-1.001, P=0.032). Conclusions:Smoking behavior among employees in heavy industry enterprises is significantly correlated with risk factors for cardiovascular and cerebrovascular diseases. The degree of tobacco dependence is closely related to the risk of abnormal fasting blood glucose, low-density lipoprotein cholesterol, and triglycerides.

Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.

Objective:To explore the funding status and research hotspots of the National Natural Science Foundation of China (NSFC) for projects in the field of TCM for the prevention and treatment of heart failure.Methods:The research projects of TCM in the prevention and treatment of heart failure funded were retrieved from NSFC Big Data Knowledge Management Service Platform from January 1, 2010 to December 31, 2023. Excel 2022 software was used to analyze the data of the number of funded projects, the amount of funding, the supporting units and the regions. VOSviewer 1.6.20 software was used to analyze the co-occurrence of keywords with frequency≥3.Results:A total of 202 research projects were funded with a total funding amount of 89.8 million RMB, and the number and amount of projects showed a fluctuating upward trend. The funding categories were mainly general programs and youth science foundation projects. There were 42 supporting units involved, and TCM universities and colleges were the main recipients of funding. Regional distribution was uneven, mainly in Beijing, Shanghai, Guangdong and other regions. There were 17 secondary discipline codes involved, and the discipline categories were concentrated in Internal Medicine of TCM (H3108), Clinical Basis of Integrative Medicine (H3302) and Cardiovascular Pharmacology of Chinese Medicine (H3209). Therapeutic modalities covered compounding, monomers, proprietary Chinese medicines, and drug pairs, and research hotspots included aspects of myocardial energy metabolism remodeling, mitochondrial autophagy, macrophage polarization, endoplasmic reticulum stress, calcium homeostasis, ferroptosis, exosomes, micro-RNAs, and so on.Conclusion:NSFC has provided strong support to the research in the field of TCM for heart failure. In the future, the supporting units should pay attention to the interdisciplinary integration and development to promote the vigorous development of TCM.