ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Objective:To analyze the clinical and ultrasonographic characteristics of papillary thyroid carcinoma(PTC)and explore their correlation with cervical lymph node metastasis(CLNM),thereby constructing a nomogram pre-diction model for assessing the risk of CLNM in PTC.Methods:A total of 553 patients(corresponding to 553 nod-ules)with papillary thyroid carcinoma(PTC),confirmed by postoperative pathology,who underwent ultrasonography and had complete clinical data at the Second Hospital of Shandong University between December 2019 and December 2022,were included.228 patients(228 nodules)hadcervical lymph node metastasis,and 325 patients(325 nodules)were without cervical lymph node metastasis.All patients were categorized into metastasis and non-metastasis groups based on the presence or absence of cervical lymph node metastasis.These groups were then randomly di-vided into training and validation sets in a 7:3 ratio.Differences in clinical and ultrasonographic characteristics between the two groups were compared,and a nomogram was constructed.Results:Univariate analysis revealed statistically significant differences between the metastasis group and the non-metastasis group in terms of age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,capsular contact,and blood flow(P<0.05).Logistic regression analysis in the training set indicated that age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,and blood flow were associated with lymph node metastasis in papillary thyroid carcinoma(PTC)(P<0.05).These indicators were incorporated into a nomogram model,which demonstrated high predictive performance,good calibration,and significant clinical utility in both the training and validation sets.Conclu-sion:The nomogram prediction model,constructed based on clinical and ultrasonographic features,effectively predicts the risk of cervical lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC).Patients who were older,had concomitant Hashimoto's thyroiditis,or exhibited a nodule aspect ratio≥1 were less likely to have concurrent CLNM.Conversely,patients presenting with multiple nodules,nodules with microcalcifications,or nodules demonstrating central or rich/peripheral vascularity were more likely to have concurrent CLNM.

This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.
Salvia miltiorrhiza/chemistry* ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Kinetics ; Quality Control ; Abietanes

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Objective:To analyze the clinical and ultrasonographic characteristics of papillary thyroid carcinoma(PTC)and explore their correlation with cervical lymph node metastasis(CLNM),thereby constructing a nomogram pre-diction model for assessing the risk of CLNM in PTC.Methods:A total of 553 patients(corresponding to 553 nod-ules)with papillary thyroid carcinoma(PTC),confirmed by postoperative pathology,who underwent ultrasonography and had complete clinical data at the Second Hospital of Shandong University between December 2019 and December 2022,were included.228 patients(228 nodules)hadcervical lymph node metastasis,and 325 patients(325 nodules)were without cervical lymph node metastasis.All patients were categorized into metastasis and non-metastasis groups based on the presence or absence of cervical lymph node metastasis.These groups were then randomly di-vided into training and validation sets in a 7:3 ratio.Differences in clinical and ultrasonographic characteristics between the two groups were compared,and a nomogram was constructed.Results:Univariate analysis revealed statistically significant differences between the metastasis group and the non-metastasis group in terms of age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,capsular contact,and blood flow(P<0.05).Logistic regression analysis in the training set indicated that age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,and blood flow were associated with lymph node metastasis in papillary thyroid carcinoma(PTC)(P<0.05).These indicators were incorporated into a nomogram model,which demonstrated high predictive performance,good calibration,and significant clinical utility in both the training and validation sets.Conclu-sion:The nomogram prediction model,constructed based on clinical and ultrasonographic features,effectively predicts the risk of cervical lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC).Patients who were older,had concomitant Hashimoto's thyroiditis,or exhibited a nodule aspect ratio≥1 were less likely to have concurrent CLNM.Conversely,patients presenting with multiple nodules,nodules with microcalcifications,or nodules demonstrating central or rich/peripheral vascularity were more likely to have concurrent CLNM.

OBJECTIVE: To investigate the clinical characteristics and prognosis of primary pulmonary lymphoma (PPL). METHODS: The clinical data of 17 patients with PPL admitted to Gansu Provincial Hospital from January 2013 to June 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: The median age of the 17 patients was 56 (29-73) years old. There were 8 males and 9 females. According to Ann Arbor staging system, there were 9 patients with stage I-II and 8 patients with stage III-IV. There were 14 patients with IPI score of 0-2 and 3 patients with IPI score of 3-4. All 17 patients had symptoms at the initial diagnosis, most of the first symptoms were cough, and 6 patients had B symptoms.Among the 17 patients, there were 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, 1 case of gray zone lymphoma (GZL), and 3 cases of Hodgkin's lymphoma (HL). 15 patients received chemotherapy, of which 3 cases received autologous hematopoietic stem cell transplantation(ASCT) and 3 cases received radiotherapy; 2 patients did not receive treatment. The median number of chemotherapy courses was 6(2-8). The short-term efficacy was evaluated, 12 patients achieved complete remission (CR) and 3 patients achieved partial remission (PR). The age, pathological subtype, sex, Ann Arbor stage, β₂-microglobulin(β₂-MG) level, lactate dehydrogenase(LDH) level were not correlated with CR rate (P >0.05), while IPI score was correlated with recent CR rate (P < 0.05 ). The median follow-up time was 31(2-102) months. One of the 12 CR patients died of COVID-19, and the rest survived. Among the 3 patients who did not reach CR, 1 died after disease progression, while the other 2 survived. One of the 2 untreated patients died one year after diagnosis. Both the median progression-free survival (PFS) time and overall survival (OS) time of the 17 patients were both 31 (2-102) months. CONCLUSION The incidence of PPL is low, and the disease has no specific clinical manifestations, which is easily missed and misdiagnosed. The pathological subtypes are mainly MALT lymphoma and DLBCL, and the treatment is mainly combined chemotherapy. The IPI score is related to the treatment efficacy.
Humans ; Middle Aged ; Male ; Female ; Adult ; Prognosis ; Aged ; Lung Neoplasms/therapy* ; Retrospective Studies ; Neoplasm Staging ; Lymphoma/therapy* ; Lymphoma, Large B-Cell, Diffuse

Objective:To analyze the clinical and ultrasonic features of breast invasive ductal carcinoma in young women patients,and improve the accuracy of ultrasonic diagnosis of breast invasive ductal carcinoma in young patients.Methods:A retrospective study was conducted on patients with invasive ductal carcinoma who underwent surgery in the Second Hospital of Shandong University from December 2015 to June 2023,with complete clinical data,preopera-tive ultrasonography and postoperative pathology.All patients were divided into two groups:young group(≤35 year-old)and control group(>35 year-old).Univariate t-test and multivariate Logistic regression analyses were used to assess the factors.Results:There was a statistical difference between the young group and the control group in the accuracy of ultrasound diagnosis(young group 81%vs control group 94%,χ2=13.082,P=0.001).Compared with the control group,the young group had a shorter disease history,a higher proportion of multiple masses,posterior echo changes and hypo-vascular lesions(P<0.05).However,there was no statistical difference in family history of breast cancer,other cancer family history,clinical symptoms,size,lesion classification,palpation,location,aspect ratio,focus echo,shape,edge per-formance,bright ring sign,calcification characteristics,ER,PR,HER-2 and Ki67(P>0.05).Conclusion:The incidence rate of young breast IDC is low,while the misdiagnosis rate of ultrasound is relatively high.More attention should be paid when the patient has a short history,multiple masses,changes in the posterior echo and less lesion blood supply.

Objective:To analyze the clinical and ultrasonic features of breast invasive ductal carcinoma in young women patients,and improve the accuracy of ultrasonic diagnosis of breast invasive ductal carcinoma in young patients.Methods:A retrospective study was conducted on patients with invasive ductal carcinoma who underwent surgery in the Second Hospital of Shandong University from December 2015 to June 2023,with complete clinical data,preopera-tive ultrasonography and postoperative pathology.All patients were divided into two groups:young group(≤35 year-old)and control group(>35 year-old).Univariate t-test and multivariate Logistic regression analyses were used to assess the factors.Results:There was a statistical difference between the young group and the control group in the accuracy of ultrasound diagnosis(young group 81%vs control group 94%,χ2=13.082,P=0.001).Compared with the control group,the young group had a shorter disease history,a higher proportion of multiple masses,posterior echo changes and hypo-vascular lesions(P<0.05).However,there was no statistical difference in family history of breast cancer,other cancer family history,clinical symptoms,size,lesion classification,palpation,location,aspect ratio,focus echo,shape,edge per-formance,bright ring sign,calcification characteristics,ER,PR,HER-2 and Ki67(P>0.05).Conclusion:The incidence rate of young breast IDC is low,while the misdiagnosis rate of ultrasound is relatively high.More attention should be paid when the patient has a short history,multiple masses,changes in the posterior echo and less lesion blood supply.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.