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*

Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

In order to investigate the mitigating effect of Yin Chen aqueous extract on liver injury induced by LPS combined with D-GalN in mice,a mouse liver injury model was established by in-traperitoneal injection of LPS and D-GalN,and the mice were group-fed by instillation of saline,bi-phenyl dibenzyl ester,and Yin Chen aqueous extract with different concentrations of LPS and D-GalN.The liver index of mice was calculated,pathological tissue sections were observed,and the expression of ALT,AST,inflammatory cytokines,oxidative stress,hepatic enzymes,and IL-17/TNF pathway were detected in serum to investigate the effects and mechanisms of the aqueous ex-tracts of Yin Chen in alleviating the liver injury in mice.The results showed that the liver index of mice in the model group was significantly elevated,the serum levels of ALT and AST were signifi-cantly elevated,the levels of IL-iβ,IL-8 and TNF-α in liver tissue were significantly elevated,the levels of IL-4 were significantly reduced,the levels of GSH-Px,CAT and SOD were significantly reduced,the levels of ROS and MDA were significantly elevated,CYP2E1 and CYP1A2 protein content and mRNA expression were significantly up-regulated,and the expression levels of TNF,TNFR1,IL-17A,ACT1 and IL-6 mRNA were significantly up-regulated.The study showed that the aqueous extract of Yin Chen had a certain alleviating effect on the liver injury caused by LPS combined with D-GalN in mice.The mechanism of action includes decreasing the metabolic level of hepatic drug enzymes,alleviating oxidative stress,inhibiting the expression of IL-17/TNF pathway and down-regulating the level of inflammatory factors in mice.

Objective:To investigate the iodine nutrition status of children aged 8 - 10 and pregnant women in Xining City, Qinghai Province.Methods:From 2019 to 2021, a stratified cluster sampling method was used to divide 7 counties (districts) under the jurisdiction of Xining City, Qinghai Province into 5 sampling areas according to east, west, south, north, and center each year. One township (town, street) was selected from each area. Forty non boarding students aged 8 to 10 from each primary school (half male and half female, age balanced) and 20 pregnant women from each township (town, street) location were selected to collect edible salt samples at home and a random urine sample to measure salt iodine and urinary iodine level. B-ultrasound was used to measure thyroid volume in children and the goiter rate was calculated.Results:A total of 6 534 samples of household edible salt were collected from children and pregnant women, with an average salt iodine concentration of 25.58 mg/kg. The coverage rate of iodized salt was 97.50% (6 371/6 534), and the qualified iodized salt consumption rate was 89.46% (5 845/6 534). A total of 4 362 urine samples were collected from children, with a median urinary iodine level of 183.10 μg/L. The difference between different years was statistically significant ( H = 20.27, P < 0.001). A total of 2 169 urine samples were collected from pregnant women, with a median urinary iodine level of 168.90 μg/L. The difference between different years was statistically significant ( H = 107.09, P < 0.001). A total of 3 336 cases of thyroid gland examination were conducted in children, including 33 cases of thyroid enlargement, with a goiter rate of 0.99%. There was a statistically significant difference between different years (χ 2 = 15.00, P < 0.001). Conclusion:From 2019 to 2021, children aged 8 to 10 and pregnant women in Xining City are at an appropriate level of iodine, and the achievements in prevention and treatment of iodine deficiency disorders still need to be continuously consolidated.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

Acupuncture is considered both safe and effective for treating depression;however,its underlying mechanism remains incompletely understood.This article reviewed the mechanisms of acupuncture in depression from the perspective of brain network dynamics.It has been found abnormal alterations in the structural and functional brain networks,including the default mode network,cognitive control network,salience network and affective network in individuals with depression.Acupuncture has been shown to enhance the diffusion anisotropy value of white matter and repair the microstructure of white matter fiber bundles in key brain regions.It can also modulate the activation the functional brain networks,either globally or in specific network segments,improve functional connectivity within and between functional networks,regulate global transmission efficiency and connectivity patterns of functional networks,restore brain network interaction balance,regulate abnormal integration of functional networks,and improve emotional regulation ability and cognitive function,in order to alleviate the clinical symptoms of depression and serve as an effective antidepressant therapy,which can provide reference for the study of acupuncture intervention in the brain network mechanism of depression.

Objective To investigate the proactive coping of schizophrenia patients with auditory hallucinations and to analyze its influencing factors.Methods A total of 240 schizophrenia patients with auditory hallucinations hospitalized in Shandong Mental Health Center from February to October 2023 were selected as subjects.General information questionnaire,simplified coping style questionnaire,perceived social support scale,insight and treatment attitude questionnaire were used to conduct the survey.Results A total of 236 valid questionnaires were collected,and effective questionnaire response rate was 98.33％.The proactive coping score of schizophrenia patients with auditory hallucinations was(18.55±7.74)points,which was at a moderate level.The results of multiple linear regression analysis showed that education level,perceived of social support,and self-awareness were the influencing factors of proactive coping to schizophrenia patients with auditory hallucinations(P＜0.05).Conclusion The proactive coping of schizophrenia patients with auditory hallucinations needs to be further improved,and nursing staff can focus on patients with low education level,low ability to perceive social support and poor self-awareness,and formulate targeted interventions to improve their proactive coping to auditory hallucinations.

OBJECTIVE: To investigate the effect of manual acupuncture manipulations (MAMs) on subcutaneous muscle tissue, by developing quantitative models of "lifting and thrusting" and "twisting and rotating", based on machine learning techniques. METHODS: A depth camera was used to capture the acupuncture operator's hand movements during "lifting and thrusting" and "twisting and rotating" of needle. Simultaneously, the ultrasound imaging was employed to record the muscle tissue responses of the participants. Amplitude and angular features were extracted from the movement data of operators, and muscle fascicle slope features were derived from the data of ultrasound images. The dynamic time warping barycenter averaging algorithm was adopted to align the dual-source data. Various machine learning techniques were applied to build quantitative models, and the performance of each model was compared. The most optimal model was further analyzed for its interpretability. RESULTS: Among the quantitative models built for the two types of MAMs, the random forest model demonstrated the best performance. For the quantitative model of the "lifting and thrusting" technique, the coefficient of determination (R²) was 0.825. For the "twisting and rotating" technique, R² reached 0.872. CONCLUSION Machine learning can be used to effectively develop the models and quantify the effects of MAMs on subcutaneous muscle tissue. It provides a new perspective to understand the mechanism of acupuncture therapy and lays a foundation for optimizing acupuncture technology and designing personalized treatment regimen in the future.
Humans ; Acupuncture Therapy/methods* ; Machine Learning ; Male ; Adult ; Female ; Subcutaneous Tissue/diagnostic imaging* ; Young Adult

Objective This study aimed to investigate the regulatory effect of electroacupuncture(EA)intervention on the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)signaling pathway in the hippocampal tissue of Alzheimer's disease(AD)model mice and its effect on astrocytic glycolytic function,further exploring how EA ameliorates AD-related cognitive impairment.Methods Eighteen APP/PS1 mice were randomly divided into model,EA,and sham EA groups(n=6)using the random number table method.Six wild-type C57BL/6J mice served as the control group.The EA group received EA stimulation at acupoints"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)(administered every other day,20 min per session,for 4 weeks).The sham EA group received identical needle insertions at the same acupoints without electrical stimulation.The control and model groups were only restrained.Cognitive function was assessed using the Morris water maze and Y-maze spontaneous alternation tests.Hippocampal morphology was observed via hematoxylin and eosin staining.Hippocampal β-amyloid peptide 1-42(Aβ1-42)deposition was detected using immunohistochemistry.HIF-1α protein expression,the p-Akt/Akt,and p-mTOR/mTOR ratios were measured using Western blotting.Pyruvate kinase M2(PKM2)and lactate dehydrogenase A(LDHA)activities were quantified using enzyme-linked immunosorbent assay.Hexokinase(HK)activity and L-lactate content were determined using a colorimetric assay.Co-localization of LDHA with the astrocyte marker glial fibrillary acidic protein was quantitatively analyzed using immunofluorescence double-labeling combined with Pearson's correlation coefficient.Results Compared with the control group,the model group mice exhibited cognitive decline,as shown by prolonged escape latency(P<0.01),reduced number of platform crossings,lower time spent in the target quadrant,and decreased spontaneous alternation accuracy(P<0.01).The hippocampal neurons showed cell body swelling,deeper nuclear staining,enlarged intercellular spaces,and increased average optical density of Aβ1-42(P<0.01).The p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,were elevated(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels were significantly increased(P<0.01),and the co-localization coefficient of LDHA with astrocytes was enhanced.Compared to the model group,the EA group of mice showed improved cognitive function.The hippocampal neurons had more intact structures,with a more uniform cell distribution.The average optical density of Aβ1-42 decreased(P<0.01),and the p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,decreased(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels decreased(P<0.05),and the co-localization coefficient of LDHA with astrocytes significantly decreased(P<0.01).No significant improvement was observed in any of the indicators in the sham EA group compared with the EA group.Conclusion EA at"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)ameliorates cognitive dysfunction in AD model mice.The underlying mechanism may involve suppressing the overactivation of the hippocampal Akt/mTOR/HIF-1α signaling pathway,thereby downregulating key glycolytic enzyme activities and reducing abnormal lactate accumulation.Furthermore,the astrocytic glycolytic metabolic pathway may constitute a key therapeutic target for this intervention.

OBJECTIVE To investigate the therapeutic effect of Qingchang Huazhuo Formula(QCHZF)on mice with ulcerative colitis(UC)and the influences of fecal metabolites based on non-targeted metabolomics to investigate the mechanism of action of QCHZF in the treatment of UC.METHODS UC mice were induced by dextran sulfate sodium salt(DSS)and were administered with QCHZF.During the experiment,the body weight,stool characteristics and blood in stool were recorded daily,and the disease activity index(DAI)was calculated.At the end of the experiment,the length of colon was measured,colonic tissue damage in mice were ob-served by hematoxylin-eosin and alcian blue staining,mRNA expression levels of inflammatory factors,IL-6,IL-18 and IL-1β,and intestinal barrier factors,ZO-1 and Muc2,were detected in colon tissues via qPCR method,and protein expression level of intestinal barrier,Muc2,was detected with immunofluorescence.Fecal metabolite changes in mice were detected employing un-targeted metabo-lomics and analyzed by MetaboAnalyst 5.0 for metabolic pathway enrichment.RESULTS QCHZF significantly alleviated colitis symptoms,increased body weight,decreased DAI score,reversed colonic shortening,inhibited inflammatory factors expression,im-proved colonic tissue structure disorders,increased the number of goblet cells,and restored the intestinal barrier in UC mice,regulated 58 metabolites,mainly involving pathways of methionine and cysteine metabolism,purine metabolism,steroid hormone biosynthesis,vitamin B6 metabolism,tryptophan metabolism and primary bile acid pathways.CONCLUSION QCHZF can improve colitis symp-toms,repaire the intestinal barrier and modulate fecal metabolites and related metabolic pathways in UC mice.