[摘 要] 目的：通过多组学整合分析，解析肠道菌群在胆管癌（CCA）发生发展中的潜在作用机制并识别相关关键基因。方法：基于SRA数据库的16S rRNA测序数据，比较CCA患者与健康对照者的肠道菌群组成；采用孟德尔随机化（MR）分析评估菌群与CCA风险的遗传关联。通过gutMGene和GeneCards数据库获取相关代谢物与基因，进行代谢和功能富集分析。整合GEO单细胞转录组数据（GSE213452），解析肿瘤微环境的细胞组成，重点关注T细胞亚群及其功能状态，并结合TCGA-CHOL数据集验证关键候选基因的表达差异。结果：与健康对照组相比，CCA患者肠道菌群组成发生显著改变，变形菌门下菌群异常富集（LDA > 4）。MR分析进一步证实，肠杆菌目与肠杆菌科的遗传易感性均与CCA风险呈正向关联。代谢通路富集分析提示，菌群相关代谢物主要参与嘌呤代谢及糖酵解/糖异生等通路；功能富集分析显示，相关基因显著富集于NOD样受体、IL-17、Toll样受体及NF-κB信号通路等炎症免疫通路。单细胞转录组分析结果显示，CCA组织中肿瘤细胞比例显著升高（P < 0.05），T细胞比例由20.7%增至39.2%；拟时序分析结果表明，MKI67⁺ T细胞处于分化末期并呈高增殖特征，其差异基因与菌群相关基因存在交集，其中SERPINA1和IFNG表达在肿瘤免疫微环境中显著变化（P < 0.001），可能发挥核心调控作用。TCGA-CHOL数据集验证显示，SERPINA1在CCA肿瘤组织中显著下调（P < 0.001），而IFNG在肿瘤与正常组织间无显著差异（P > 0.05）。结论：肠道菌群失衡（尤其是肠杆菌科异常增殖）可能通过代谢-免疫调控网络促进CCA进展，T细胞功能变化与关键基因（SERPINA1和IFNG）在MKI67+ T细胞中的差异化表达模式密切相关。

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

The aim of this study was to investigate the improvement effect of Wenpi Pills(WPP) on non-alcoholic fatty liver disease(NAFLD). The experiment was divided into two parts, using C57BL/6 mouse models induced by a high-fat diet(HFD) and a methionine and choline deficiency diet(MCD). The HFD-induced experiment lasted for 16 weeks, while the MCD-induced experiment lasted for 6 weeks. Mice in both parts were divided into four groups: control group, model group, low-dose WPP group(3.875 g·kg~(-1), WPP＿L), and high-dose WPP group(15.5 g·kg~(-1), WPP＿H). After sample collection from the HFD-induced mice, lipid content in the serum and liver, liver function indexes in the serum, and hepatic pathology were examined. Real-time fluorescent quantitative reverse transcription PCR(qRT-PCR) was used to detect the expression of lipid-related genes. After sample collection from the MCD-induced mice, serum liver function indexes and inflammatory factors were measured, and hepatic pathology and lipid changes were analyzed by hematoxylin-eosin(HE) staining and widely targeted lipidomic profiling, respectively. The results from the HFD-induced experiment showed that, compared with the HFD group, WPP administration significantly reduced the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol(TC) in the serum, with the WPP＿H group showing the most significant improvement. HE staining results indicated that, compared with the HFD group, WPP treatment improved the morphology of white adipocytes, reducing their size, and alleviated hepatic steatosis and lipid droplet accumulation. The qRT-PCR results suggested that WPP might increase the mRNA expression of liver cholesterol-converting genes, such as liver X receptor α(LXRα) and cytochrome P450 family 27 subfamily A member 1(CYP27A1), as well as lipid consumption genes like peroxisome proliferator-activated receptor α(PPARα) and adenosine mono-phosphate-activated protein kinase(AMPK). Meanwhile, WPP decreased the mRNA expression of lipid synthesis genes, including fatty acid synthetase(FAS), stearoyl-CoA desaturase 1(SCD1), and sterol regulatory element-binding protein 1c(SREBP-1c), thereby reducing liver lipid accumulation. The results from the MCD-induced experiment showed that, compared with the MCD group, WPP administration reduced the levels of ALT, AST, and inflammatory factors in the serum, thereby alleviating liver injury and the inflammatory response. HE staining of liver tissue indicated that WPP effectively improved hepatic steatosis. Non-targeted lipidomics analysis showed that WPP improved lipid metabolism disorders in the liver, mainly by affecting the metabolism of TG and cholesterol esters. In conclusion, WPP can improve hepatic lipid accumulation in NAFLD mice induced by both HFD and MCD. This beneficial effect is primarily achieved by alleviating liver injury and inflammation, as well as regulating lipid metabolism.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Lipid Metabolism/drug effects* ; Mice ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Diet, High-Fat/adverse effects* ; Liver/drug effects* ; Humans ; Disease Models, Animal ; Methionine

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

PURPOSE: Bone cement-reinforced fenestrated pedicle screws (FPSs) have been widely used in the internal fixation and repair of the spine with osteoporosis in recent years and show significant improvement in fixation strength and stability. However, compared with conventional reinforcement methods, the advantages of bone cement-reinforced FPSs remain undetermined. This article compares the effects of fenestrated and conventional pedicle screws (CPSs) combined with bone cement in the treatment of osteoporosis. METHODS: A clinical control study of FPSs and CPSs combined with bone cement reinforcement in osteoporotic vertebral internal fixation was performed using the database PubMed, Embase, Cochrane Library, CNKI, the Wanfang, and the China Biomedical Literature Service System. Two evaluators screened the relevant literature in strict accordance with the inclusion criteria (diagnosis of participants, type of clinical study, treatment with FPS and CPS, and outcome indicators) and exclusion criteria (duplicate literature and missing or incorrect data) and independently conducted data extraction and quality evaluation. Clinical control studies of direct comparison between FPS and CPS combined with bone cement reinforcement in patients who were definitively diagnosed with thoracolumbar fractures or spinal degenerative diseases were included. Quality evaluation was conducted using the Cochrane risk bias evaluation tool for randomized controlled studies and using the Newcastle-Ottawa scale for retrospective case-control studies. RevMan software (version 5.3) was used for the meta-analysis to compare the clinical efficacy, radiological results, and related complications of the 2 methods. RESULTS: A total of 13 articles were included, including 7 randomized controlled studies and 6 retrospective case-control studies. There were 909 patients in these studies, 451 in the FPS and polymethyl methacrylate (FPS & PMMA) group and 458 in the CPS and polymethyl methacrylate (CPS & PMMA) group. The results of the meta-analysis showed that there was no significant difference between the 2 groups in operation time, hospital stay, visual analogue score, Japanese orthopaedic association score, Oswestry disability index score, Cobb angle, vertebral body deformation index and fusion rate (p > 0.05). The mean difference of intraoperative bleeding volume was -10.45, (95% confidence intervals (CI) (-16.92, -3.98), p = 0.002), the mean difference of loss height of the anterior edge of the vertebral body after surgery was -0.69 (95% CI (-0.93, -0.44), p < 0.001), and the relative risk (RR) of overall complication rate was 0.43 (95% CI (0.27, 0.68), p < 0.001), including the RR of bone cement leakage rate was 0.57 (95% CI (0.39, 0.85), p = 0.005). The screw loosening rate (RR = 0.26, 95% CI (0.13, 0.54), p < 0.001) of the FPS group was significantly lower than that of the CPS group. CONCLUSION The existing clinical evidence shows that compared with the CPS combined with bone cement, the use of FPS repair in the internal fixation of an osteoporotic vertebral body can reduce the amount of intraoperative bleeding, be more conducive to maintaining the height of the vertebral body, and significantly reduce the incidence of postoperative complications such as bone cement leakage and screw loosening.
Humans ; Pedicle Screws ; Bone Cements ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Fracture Fixation, Internal/instrumentation*

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with IgD multiple myeloma (MM). METHODS: The clinical data of 8 patients with IgD MM admitted to Gansu Provincial Hospital from September 2013 to February 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: Among the 8 enrolled patients, there were 4 males and 4 females, with a median age of 60 (44-74) years. All patients had symptoms of renal insufficiency and anemia. There were 3 cases of bone invasion, 3 cases of splenomegaly, 7 cases of IgD-λ type, and 1 case of IgD-κ type. FISH examination was performed in 7 cases, and 6 of them were positive for 1q21 . There were 6 cases in DS stage III and 2 cases in DS stage II; According to ISS staging, there were 6 cases in stage III, 1 case in stage II, and 1 case in stage I; According to R-ISS staging, there were 5 cases in stage III and 3 cases in stage II. All patients received bortezomib-based combination chemotherapy, with 1 case undergoing autologous stem cell transplantation (ASCT) and 2 cases receiving daratumumab in combination. The median treatment period was 6 (1-15) cycles. The short-term efficacy was evaluated after 4-6 courses of treatment. Among the 6 patients with assessable efficacy, 1 case experienced disease progression (PD), and 5 cases achieved complete remission (CR). The median follow-up time was 26 (11-33) months, and the median progression-free survival (PFS) and median overall survival (OS) of the patients were 11.25 (3-26) months and 18.5 (4-33) months, respectively. Among the 8 patients, 4 cases died. Among the deceased patients, 3 cases were in R-ISS stage III and 3 cases were 1q21 positive. 2 of the 5 patients with early CR died due to disease progression. CONCLUSION The incidence of IgD MM is low, the symptoms of early renal damage, blood system damage and bone erosion in IgD MM patients are obvious, and the median survival time is short. ASCT and / or daratumumab may bring lasting relief for IgD MM patients, but large-scale clinical studies are still needed.
Humans ; Multiple Myeloma/therapy* ; Middle Aged ; Male ; Female ; Aged ; Prognosis ; Immunoglobulin D ; Adult ; Retrospective Studies

OBJECTIVE: To explore the significance of the plasma cell percentage and immature plasma cells in the prognosis of patients with multiple myeloma (MM). METHODS: The clinical data of 126 newly diagnosed MM patients in Gansu Provincial Hospital from June 2017 to November 2022 were retrospectively analyzed. The enrolled patients were divided into a higher plasma cell percentage group (group A) and a lower plasma cell percentage group (group B) according to the median plasma cell percentage (33.5%). The clinicopathological data of the two groups were compared, and the effect of plasma cell percentage on the prognosis of MM patients was analyzed using survival curves. On this basis, group A and group B were divided into subgroups with immature plasma cells (A1 group, B1 group) and subgroups without immature plasma cells (A2 group, B2 group), respectively, then the survival curves were used to analyze the effect of immature plasma cells on the prognosis of MM patients. RESULTS: Among the 126 patients with MM, the proportions of patients with ISS stage III, elevated β₂-microglobulin(β₂-MG) level, and immature plasma cells in Group A were significantly higher compared those in Group B ( P =0.015, P =0.028, P =0.010). The median overall survival(OS) and progression-free survival(PFS) of group A were 32 months and 10 months, respectively. The median OS of group B was not reached, and the median PFS was 32 months. The 3-year OS rates of patients in group A and group B were 46.7% and 62.2%, respectively ( P =0.021), and the 3-year PFS were 29.2% and 42.5%, respectively ( P =0.033). There were no significant differences in OS and PFS between group A1 and group A2, or between group B1 and group B2 ( P >0.05). Multivariate COX survival analysis showed that the plasma cell percentage ≥33.5%（HR=1.253, 95%CI : 0.580-2.889, P =0.018）, age ≥65 years (HR=2.206, 95%CI : 1.170-3.510, P =0.012), lactate dehydrogenase(LDH) ≥250 U/L (HR=1.180, 95%CI : 0.621-2.398, P =0.048) and β₂-MG ≥3.5 mg/L (HR=1.507, 95%CI : 0.823-3.657, P =0.036) were independent risk factors affecting OS in MM patients. CONCLUSION MM patients with a higher plasma cell percentage (≥33.5%) at the initial diagnosis have a later disease stage, poorer OS and PFS, compared to the patients with a lower percentage(<33.5%) of plasma cells. The presence or absence of immature plasma cells has no significant impact on the survival of MM patients.
Humans ; Multiple Myeloma/pathology* ; Prognosis ; Plasma Cells/cytology* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Bone Marrow

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with T-cell large granular lymphocytic leukemia (T-LGLL). METHODS: The clinical data of 7 patients with T-LGLL in Gansu Provincial Hospital from March 2016 to June 2023 were analyzed retrospectively. RESULTS: Among the 7 patients, 5 were male and 2 were female, with a median age of 51(28-83) years old. At the onset of illness, 6 cases showed symptoms of fatigue and anemia, 4 cases had enlarged lymph nodes, and 5 cases had splenomegaly. Examination showed that 4 cases were antinuclear antibody(ANA) positive, 5 cases were anemia. The median hemoglobin (Hb) level was 83(61-151) g/L, the median white blood cell count (WBC) was 5.6(2.0-8.7)×10⁹ /L, and the median percentage of lymphocytes in peripheral blood was 66.2(13.9-89.1)%. There were 3 cases with extremely active bone marrow hyperplasia, 2 cases with active hyperplasia, and 2 cases with decreased hyperplasia. There were 5 cases with mild myelofibrosis (MF-1), and 1 case with moderate myelofibrosis (MF-2). The median percentage of T cells was 64.3 (31.5-80.6)%. 5 cases showed the classic immunophenotype (CD3 ⁺ CD4^- CD8 ⁺), 6 cases were CD57 ⁺, 3 cases were TCRα/β ⁺, and 3 cases were TCRγ/δ ⁺. TCRG rearrangement was detected in 5 cases.The median follow-up time was 55(4-87) months, one patient died of heart disease, and the other 6 patients are surviving. CONCLUSION The incidence of T-LGLL is low. The initial symptoms of T-LGLL include anemia, fatigue, lymph node enlargement, splenomegaly, and higher percentage of lymphocytes in peripheral blood, the percentage of abnormal T cells in bone marrow was significantly increased. Analysis of flow cytometric immunophenotyping, TCR gene rearrangement, and hot spot genes such as STAT3 and STAT5b, can improve the diagnostic accuracy.
Humans ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Male ; Middle Aged ; Female ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; Retrospective Studies