ObjectiveTo study the characteristics of the five tones of Parkinson's disease （PD） patients based on the theory of "five-viscera phonology"， and provide references for the syndrome differentiation and treatment of PD. MethodsA total of 272 cases of PD patients were collected as the PD group， and 240 individuals， including patient family members and hospital staff， were recruited as the control group. The 25-tone analyzer was used to collect the five-tone characteristics of both PD patients and control group participants. The participants were then stratified into three age groups， 41~55， 56~70， and 71~85 years old， and categorized by gender （male and female） for analysis. The frequency and composition ratio of the five tones were analyzed for both groups across the different age ranges and genders. Additionally， the average voice frequency of each participant was calculated to compare differences between groups， stratified by age range and gender. ResultsIn the 41~55 and 56~70 age groups， male participants in the PD group and the control group exhibited the highest frequency of Yu （羽） tone， with the PD group showing a significantly higher composition ratio of Yu tone compared to the control group （P＜0.05）； for males in the 56~70 age group， the composition ratios of Shang （商） and Zhi （徵） tone in the PD group were lower than those in the control group （P＜0.05）. For males in the 71~85 age group， both the PD group and the control group had the highest frequency of Yu tone， but there was no statistically significant difference in the composition ratios of the five tones between groups （P＞0.05）. For female participants in the PD group across all age groups， Yu tone was the most frequent， whereas for the control group， Jue （角） tone was the most frequent in all age groups， and the composition ratio of Yu tone in the PD group was significantly higher than that in the control group across all age groups （P＜0.05）； in the 56~70 age group， the composition ratio of Jue tone was lower in the PD group compared to that in the control group （P＜0.05）. Regarding voice frequency， males in the PD group aged 41~55 and 56~70 had higher voice frequency than those in the control group of the same age range， and similarly， females in the PD group aged 56~70 and 71~85 had higher voice frequency than their counterparts in the control group （P＜0.05）. ConclusionPD patients have a voice with a higher frequency and an increased proportion of Yu tone in their five-tone distribution. According to the theory of five-viscera phonology， PD patients may have disease mechanism of kidney essence deficiency.

Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

ObjectiveTo explore the possible mechanism of action of Bushen Huoxue Granules （补肾活血颗粒， BHG） in the treatment of Parkinson's disease （PD） through the Nrf2/NLRP3 inflammasome axis. MethodsA total of 84 male C57/BL 6 mice were randomly divided into blank group， model group， Madopar group， dimethyl fumarate group， and low-， medium， and high-dose BHG group， with 12 mice in each group. Except for the blank group， all groups were induced into PD models by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 30 mg/ml for 7 consecutive days. The blank group received an equal volume of saline. After model establishment， the low-， medium， and high-dose BHG groups were treated with 1.5， 3， and 6 g/（kg·d） of the BHG by gavage， respectively. The Madopar group was given 0.113 g/（kg·d） of Madopar tablets by gavage， and the dimethyl fumarate group was given 50 mg/（kg·d） of dimethyl fumarate solution. The blank group and the model group were given 10 ml/（kg·d） of distilled water by gavage. Gavage was administered once daily for 14 days. Behavioral changes were evaluated using the open field test （total distance， central area distance， and average speed）， rotarod test （time on the rod）， and climbing pole test （climbing time）. Serum levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and myeloperoxidase （MPO） were measured by ELISA. Immunohistochemistry was used to detect tyrosine hydroxylase （TH） expression in the brain substantia nigra. Immunofluorescence was used to detect α-synuclein （α-syn） expression. Western Blot was used to detect Nrf2， NLRP3， Caspase-1， and α-syn protein levels in the brain substantia nigra. RT-PCR was used to detect mRNA expression levels of Nrf2， NLRP3， and Caspase-1 in the brain substantia nigra. ResultsCompared with the blank group， the model group showed decreased total distance， central area distance， and average speed， reduced time on the rotarod， prolonged climbing time， reduced TH expression， increased α-syn expression， decreased Nrf2 protein and mRNA expression， increased NLRP3 and Caspase-1 protein and mRNA expression， and elevated serum IL-1β， IL-18， and MPO levels （P＜0.05）. Compared with the model group， all drug interventions significantly improved the above indicators （P＜0.05）. There was no significant differences in all indicators between the high-dose BHG group and the Madopar group （P＞0.05）. Compared with the dimethyl fumarate group， the medium and high-dose BHG groups showed increased Nrf2 mRNA expression in the brain substantia nigra （P＜0.05）. Compared with the high-dose BHG group， the low-dose group showed decreased total distance， central area distance， and average speed， reduced serum IL-18 levels， decreased α-syn， Nrf2， NLRP3， and Caspase-1 protein levels， and lower Nrf2 mRNA expression （P＜0.05）. ConclusionThe mechanism by which BHG treat PD may involve activating the Nrf2/NLRP3 inflammasome axis in the brain substantia nigra， thereby reducing neuroinflammation and α-syn aggregation. The high-dose group showed the best effects.

Objective To analyze the effect of residual cholesterol (RC) on hearing loss in noise-exposed workers. Methods A total of 3 412 workers engaged in noise operation work in an underground railway enterprise were selected as the research subjects using the judgment sampling method. Their occupational health examination data were collected to analyze the relationship between RC and hearing loss. Results The noise intensity of workplace in the underground rail enterprise was 80.0-85.0 (81.4±3.2) dB(A). The detection rate of hearing loss was 20.2% (691/3 412). The rates of abnormal total cholesterol, triacylglycerol, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol were 35.6%, 25.7%, 9.5% and 42.4%, respectively. The median and the 25th and 75th percentiles [M(P₂₅,P₇₅)] of RC level were 0.24 (0.15, 0.37) mmol/L. The levels of total cholesterol, triacylglycerol and RC of workers in hearing loss group were higher than those in normal hearing group [M(P₂₅,P₇₅): 4.91(4.37, 5.58) vs 4.84(4.30, 5.46) mmol/L, 1.29(0.91, 1.93) vs 1.16(0.82, 1.67) mmol/L, 0.26(0.16, 0.41) vs 0.24(0.14, 0.37) mmol/L, all P<0.05]. The detection rate of hearing loss in abnormal triglyceride group was higher than that in normal triglyceride group (24.8% vs 18.7%, P<0.01), and the detection rate of hearing loss in abnormal HDL-C group was higher than that in normal HDL-C group (25.0% vs 19.8%, P<0.05). The higher the serum RC level, the higher the detection rate of hearing loss (P<0.01). Multivariate logistic regression result showed that individual with older age, longer work time and higher serum RC level had higher risk of hearing abnormality (all P<0.05), and the risk of hearing abnormality was higher in patients with abnormal fasting blood glucose than patients with normal faseing blood glucose (P<0.05) after controlling for confounding factors such as gender, alcohol consumption, body mass index, and elevated blood pressure. However, abnormal triacylglycerol and HDL-C levels were not significantly related to the risk of hearing abnormality (both P>0.05). Conclusion Serum RC levels are an independent risk factor for hearing loss among noise-exposed workers exposed to noise level of 80.0-85.0 dB(A) in the workplace.

Background Hypertension is one of the chronic diseases with the highest prevalence in China, and a history of hypertension may potentially exacerbate hearing loss. Investigating the association between long-term blood pressure trends and hearing thresholds could contribute to hearing protection efforts for occupationally noise-exposed populations. Objective By investigating hearing thresholds and blood pressure levels among occupationally noise-exposed workers in an urban rail transit enterprise, and conducting a comprehensive analysis of the association between long-term blood pressure changes and hearing thresholds, to provide data references for health management strategies targeting occupationally noise-exposed workers. Methods Workers exposed to occupational noise at a rail transit enterprise were enrolled as study subjects and underwent pure-tone audiometry. Group-based trajectory modeling was employed to identify blood pressure trajectories. Categorical data were compared using chi-square tests, while normally distributed continuous variables were analyzed via t-tests and analysis of variance (ANOVA). Generalized linear mixed models (GLMMs) were subsequently applied toexamine associations between these trajectory groups and high-frequency hearing thresholds. Results Among 2 002 occupationally noise-exposed workers, the median (P₂₅, P₇₅) age was 32 (28, 35) years, with a median (P₂₅, P₇₅) working tenure of 7 (3, 10) years. In 2019, the positive hypertension rate was 9.04%, with a mean systolic blood pressure (SBP) of (122.97±11.60) mmHg and a mean diastolic blood pressure (DBP) of (76.37±9.02) mmHg. The hearing loss prevalence was 10.1%, showing bilateral high-frequency average hearing thresholds of (17.18±8.71) dB and speech-frequency average thresholds of (13.79±3.46) dB. Three distinct trajectory groups were identified for both SBP and DBP. Compared with other trajectory groups, the high-stable DBP group exhibited significantly higher hearing loss prevalence (χ²=6.34, P=0.042) and elevated high-frequency hearing thresholds (all Ps<0.05). Specifically, within the 30-39 age subgroup, the moderate-stable DBP group demonstrated 1.96 dB lower high-frequency thresholds than the high-stable group [β(95%CI): −1.96 (−3.61, −0.32), P=0.020]. Conclusion Among occupationally noise-exposed workers in a municipal rail transit enterprise, DBP trajectories demonstrated a positive association with high-frequency hearing thresholds. Notably, in young and middle-aged occupationally noise-exposed populations, DBP may exert a more critical influence than SBP on the progression of hearing loss.

Background The Inner Mongolia Autonomous Region is a vast area with a wide array of ecological environments, resulting in considerable regional variations in air pollution characteristics. Current research is limited by a scarcity of systematic, region-wide studies and risk assessments. Objective To assess the health risks associated with inhalation exposure to nine heavy metal and metalloid elements in atmospheric fine particulate matter (PM_2.5) for the population of the Inner Mongolia Autonomous Region. Methods From the 10th to the 16th of each month throughout 2023, atmospheric PM_2.5 samples were collected at designated monitoring sites in 12 leagues (cities) across the Inner Mongolia Autonomous Region to analyze the characteristics and trends in concentration. The health risk assessment model developed by the United States Environmental Protection Agency was employed to evaluate both the non-carcinogenic and carcinogenic risks associated with the heavy metal elements beryllium (Be), cadmium (Cd), chromium (Cr), hydrargyrum (Hg), plumbum (Pb), manganese (Mn), and nickel (Ni) and the metalloid elements stibium (Sb) and arsenic (As). Results In 2023, a total of 1206 valid PM_2.5 samples were analyzed from the Inner Mongolia Autonomous Region. The annual average PM_2.5 concentrations in Inner Mongolia, as well as in the cities of Ordos, Wuhai, and the Alxa League, all exceeded the national limit of 35 μg·m⁻³. The PM_2.5 concentrations across the leagues (cities) exhibited a clear seasonal variation, peaking in winter, followed by spring, and reaching a minimum in summer and autumn. The median PM_2.5 concentration in Ordos throughout the year was higher than that in the other leagues (cities) of the region. Concerning health risks, the non-carcinogenic risks associated with the 9 elements detected in each league (city) were all below 1, indicating acceptable levels. However, the non-carcinogenic risk values for Mn, Cr, and As were relatively high; specifically, Ordos City displayed the highest non-carcinogenic risk values for Mn (7.74×10⁻¹) and Cr (2.97×10⁻²), while Chifeng City recorded the highest value for As (2.34×10⁻³). The carcinogenic risk values for As, Cd, Cr, and Ni fell within the range of 1×10⁻⁹ to 1×10⁻⁵, representing an acceptable level. The health risks varied with age, and the elderly residents faced the highest non-carcinogenic and carcinogenic health risks. Conclusion While the carcinogenic and non-carcinogenic risks from heavy metals and metalloids within atmospheric PM_2.5 in the Inner Mongolia Autonomous Region are generally within acceptable limits, the potential risks that Mn, As, and Cr pose to the health of elderly people warrants particular attention, and Ordos and Chifeng cities exhibit notably higher health risks among other areas. It is recommended that regular, long-term monitoring be conducted, taking into account the specific conditions at monitoring sites across each league (city), and that targeted air quality management strategies be implemented to protect public health.

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

Objective To analyze the problems found in the on-site quality assessment of occupational medical examination (OME) institutions in Guangdong Province. Methods A total of 150 OME institutions were selected as the research subjects from Guangdong Province in 2023 using a random number table method. The on-site quality assessment was conducted by listening to reports, meeting discussion, on-site inspection, data review and human-machine assessment. The relevant assessment results were analyzed. Results Occupational disease prevention and treatment institutes (institutes, centers) and disease control and prevention centers (hereinafter referred to as "occupational prevention institutions"), public hospitals, and private institutions accounted for 8.7%, 51.3%, and 40.0% respectively. The top three categories of registered inspections were physical factors, chemical factors and dust, accounted for 98.0%, 96.7% and 96.0%, respectively, among the 150 OME institutions. A total of 1 063 rectification items were identified, and the average number of rectification items identified per occupational prevention institutions, public hospitals and private institutions was four, six and nine, respectively. The rectification rates of the four modules of quality assessment from high to low were OME work quality control, quality management system, organizational structure, and OME information reporting, accounted for 53.2%, 23.3%, 13.7% and 9.7%, respectively. The coincidence rate from high to low of occupational reporting of noise-exposure, dust-exposure, and other hazard-exposure was 92.5%, 91.1%, and 93.4%, respectively. The on-site failure rate of quality control director, technical director, chief physician, pneumoconiosis film reader, audiometry reader and pulmonary function examination operator accounted for 15.3%, 12.7%, 8.0%, 6.7%, 6.0% and 2.7%, respectively. Institutions capable of conducting registered and partially registered OME accounted for 90.7% and 6.0%, respectively. The five institutions that were unable to conduct registered OME were private institutions. A total of five private institutions were found to be suspected of illegal and irregular activities. Conclusion The problems of OME in the on-site quality assessment of OME institutions in Guangdong Province were mainly quality control. Private institutions had more prominent problems in various aspects. It is necessary to strengthen the training of key personnel such as technical directors, quality control directors, and chief physicians.

Objective To investigate the correlation between preoperative N-terminal pro-B-type natriuretic peptidogen(NT-proBNP)levels and early postoperative outcomes in elderly and critically ill pa-tients with hip fractures.Methods A total of 593 elderly and critically ill patients with hip fractures from January 2018 to April 2021 were selected,including 189 males and 404 females,aged≥65 years,BMI 12.0-35.5 kg/m2,ASA physical status Ⅱ-Ⅳ.General preoperative information,intraoperative and post-operative discharge outcomes of patients were retrospectively obtained by the electrical clinical medical record system or telephone follow-up.The receiver operator characteristic(ROC)curve of preoperative plas-ma NT-proBNP and postoperative 30-day death was plotted,and the corresponding optimal cut-off value was 1 765.0 pg/ml.According to NT-proBNP values,the patients were divided into two groups:low-ratio group(NT-proBNP≤1 765.0 pg/ml,group L,n = 463)and high-ratio group(NT-proBNP＞1 765.0 pg/ml,group H,n = 130).The correlation between different plasma concentrations of NT-proBNP before surgery and ICU length of stay,total length of stay,postoperative complications,and 30-day mortality rate were an-alyzed using univariate and multivariate logistic regression analysis.Results Compared with group L,age,preoperative comorbidities with coronary heart disease,arrhythmia,chronic heart failure,lung disease,and chronic kidney disease,as well as mortality within 30 days after surgery were significantly increased in group H(P＜0.05).The multivariate logistic regression analysis showed that high preoperative plasma NT-proBNP concentration was positive correlation with postoperative ICU length of stay(OR = 1.215,95%CI 1.073-1.375,P = 0.020)and 30-day mortality rate(OR = 32.696,95%CI 7.158-149.338,P＜0.001).Conclusion High preoperative plasma NT-proBNP concentration is positive correlation with postoperative ICU hospitalization timeand 30-day mortality.

ObjectiveTo explore the possible mechanism of Bushen Huoxue Formula （补肾活血方， BHF） in the treatment of Parkinson's disease （PD） from the the perspective of intestinal flora. MethodsSeventy-two male C57/BL6J mice were randomly divided into blank group， model group， Madopar group and low-， medium- and high-dose BHF groups， with 12 mice in each group. The mice in the blank group were intraperitoneally injected with 10 ml/kg of normal saline， and those in the other groups were intraperitoneally injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 3 mg/ml to induce PD mice model， both once a day for 7 consecutive days. After successful modeling， the low-， medium-， and high-dose BHF groups were given 7.5， 15， and 30 g/（kg·d） of BHF by gavage， respectively， while the Madopar group was given 112.5 mg/（kg ·d） of Domedopar tablets by gavage， and the blank group and the model group were given 15 ml/（kg·d） of distilled water， all once a day for 14 consecutive days. The rod climbing test， rotating rod test， grip strength test and weight-bearing swimming test were used to evaluate the behavioral indicators of mice. Western blotting was used to measure the protein expression levels of Toll-like receptor （TLR）/nuclear factor kappa B （NF-κB） pathway inflammatory factors in the mouse ileum， including Toll-like receptor 2 （TLR2）， Toll-like receptor 4 （TLR4）， NF-κB， tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6）， and interleukin 17 （IL- 17）. 16S rRNA high-throughput sequencing was used to analyze changes in mouse intestinal flora. ResultsCompared to those in the blank group， the mice in the model group had longer bottoming time when climbing the pole， reduced grip strength， shortened rotary pole duration and swimming duration， and increased protein expression levels of TLR2， TLR4， NF-κB， TNF-α， and IL-6 in the ileal tissue （P＜0.01）. Compared to the model group， the Madopar group and the low-， medium- and high-dose BHF groups had shortened bottoming time of the climbing pole and increased grip strength； the Madopar group and the high-dose BHF group had prolonged rotary pole duration， and reduced protein expressions of TLR2， TLR4， NF-κB， TNF-α， IL-6， and IL-17 levels； and only the high-dose BHF group had prolonged swimming duration （P＜0.05 or P＜0.01）. Compared to those in the low-dose BHF group， the bottoming time of the climbing pole were shorter in the moderate- and high-dose groups （P＜0.05 or P＜0.01）， and the grip strength increased while the protein expression levels of TLR2， TLR4 and IL-17 decreased in the high-dose group （P＜0.05 or P＜0.01）. The intestinal flora results showed significant differences between the blank group and the model group in the Dominance index， Pielou_e index， Shannon index， and Simpson index （P＜0.05 or P＜0.01）. Compared to those of the model group， the Shannon index， Chao1 index， and Observed_otus index of the Madopar group， as well as the Chao1 index， Observed_otus index， Dominance index， Pielou_e index， Shannon index， and Simpson index of the high-dose BHF group all showed significantly statistical differences （P＜0.05 or P＜0.01）. At the phylum level， the relative abundance categories of bacterial phyla with statistically significant differences in each group included Proteobacteria， Bacteroidetes， and Firmicutes （P＜0.05 or P＜0.01）. At the genus level， the relative abundance categories of bacterial genera with statistically significant diffe-rences among each group included Muribaculaceae， Akkermansia， and Helicobacter pylori （P＜0.05 or P＜0.01）. ConclusionThe possible mechanism of BHF in treating PD may be to reconstruct the disordered intestinal flora structure and improve the inflammatory response.