ObjectiveTo explore the mechanism of action of Wendantang on ApoE^-/- hyperlipidemic mice using non-targeted metabolomics technology. MethodsMale C57BL/6J mice served as the normal control group （n=6）， and they were fed with regular chow， while male ApoE^-/- mice constituted the high-fat group （n=30）， and they were fed with a 60% high-fat diet. After 11 weeks of model establishment， the mice in the high-fat group were randomly divided into the model group， simvastatin group （3.3 mg·kg^-1）， and high-dose， medium-dose， and low-dose groups of Wendantang （26， 13， 6.5 g·kg^-1， respectively， in terms of crude drug amount）， with six mice in each group. The normal control group and the model group were gavaged with an equivalent volume of normal saline， and all groups continued to be fed their respective diets， receiving daily medication for 10 weeks with weekly body weight measurements. Serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， free fatty acids （NEFA）， blood glucose （GLU）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were detected in the mice. Pathological changes in liver tissue were observed using hematoxylin-eosin （HE） staining， and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS） was employed for metabolomic analysis of mouse liver tissue. ResultsCompared to the normal control group， the model group exhibited significantly increased body weight， blood lipid levels， and liver function （P<0.05， P<0.01）， with disordered liver tissue structure， swollen hepatocytes， and accompanying vacuolar fatty degeneration and inflammatory cell infiltration. Compared to the model group， the simvastatin group and Wendantang groups showed significantly reduced body weight， TG， NEFA， GLU， ALT， and AST levels （P<0.05， P<0.01）， with a significant increase in HDL-C levels （P<0.05， P<0.01）， demonstrating a dose-dependent effect. The lesion of the liver tissue section was obviously improved after administration， tending towards a normal liver tissue morphology. Analysis of liver metabolites revealed 86 differential metabolites between the normal control group and the model group， with the high-dose group of Wendantang able to regulate 56 of these metabolites. Twenty-two differential metabolites associated with hyperlipidemia were identified， mainly including chenodeoxycholic acid， hyocholic acid， taurine， glycocholic acid， dihydroceramide， hydroxy sphingomyelin C14∶1， arachidonic acid， and linoleic acid， enriching 22 metabolic pathways， with 4 being the most significant （P<0.05）， namely primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways. ConclusionWendantang can improve blood lipid levels and liver function in ApoE^-/- hyperlipidemic mice， which may be related to the regulation of primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

OBJECTIVE To analyze and evaluate serious adverse drug reaction(SADR) and drug-drug interactions(DDIs) in the real-world, so as to obtain the clinical evidence of DDIs-related SADR, and to provide a reference for rational clinical use. METHODS The SADR reports reported to the National Adverse Drug Reaction Monitoring Center from January 2011 to December 2020 were collected, and Lexi-Interaction® software in UpToDate was used to analyze ≥2 drugs in SADR to evaluate whether there were potential DDIs. And the possible adverse drug reactions caused by DDIs were statistically analyzed. RESULTS Among the 360 cases of SADR, males were slightly more than females(50.83% vs 49.17%), the mean age was (65.27±14.71) years old, and 56.39% were ≥65 years old. Cardiovascular agents were the most common implicated pharmacological group, and the gastrointestinal system was the most frequently affected system, and aspirin was the most frequently reported drug. Among 150 cases of SADR with at least two suspected drugs, 64 cases had potential DDIs, while 42 cases had clinically significant DDIs, of which only 16 and 2 cases of SADR were caused by actual DDIs in category D and X, respectively. The majority of reports(71.43%) were caused by additive pharmacodynamic interactions. Aspirin was the most common drug in both potential DDIs and actual DDIs, while aspirin and clopidogrel was the most commonly involved drug pair in actual DDIs, with gastrointestinal bleeding being the most common SADR. CONCLUSION Attention should be paid to the influence of drug interactions on SADR, and prescription should be optimized, especially in the elderly population. According to the results of potential DDIs, therapeutic drugs should be rationally selected. Meanwhile, monitoring of cardiovascular drugs and key populations should be strengthened to ensure drug safety.

Objective:To explore the genetic etiology for a patient with Alstr?m syndrome (ALMS) presenting as dilated cardiomyopathy.Methods:A 41-year-old male patient who had presented at the Sixth Medical Center of PLA General Hospital on October 20, 2021 was selected as the study subject. Clinical and laboratory examinations were carried out. Whole exome sequencing (WES) was employed for genetic testing, and candidate variants were validated by Sanger sequencing and pathogenicity analysis.Results:The patient had a 14-year medical history characterized by dilated cardiomyopathy, complete atrioventricular block, visual impairment, sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes, hypertension, renal dysfunction, and paranoid delusions. Genetic testing revealed that he has harbored compound heterozygous variants of the ALMS1 gene, namely c. 6823C>T (p.Arg2275Ter) and c. 9442_9445dup (p.Ser3149LysfsTer2). Sanger sequencing confirmed that they were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1_VeryStrong+ PM2_Supporting+ PM3+ PP3, PVS1_VeryStrong+ PM2_Supporting+ PM3). Literature review indicated that the complete atrioventricular block in the patient was a phenotype unreported previously. Conclusion:The c. 6823C>T (p.Arg2275Ter) and c. 9442_9445dup (p.Ser3149LysfsTer2) compound heterozygous variants of the ALMS1 gene probably underlay the pathogenesis in this patient. Above findings have expanded the phenotypic spectrum of ALMS and provided insights for clinicians dealing with similar cases.

To explore the prevalence and related risk factors of osteoporosis (OP) in the elderly ≥60 years old in Jiuting Town, Songjiang District, Shanghai City. A total of 2 175 local residents aged ≥60 years old who participated in the questionnaire survey at the physical examination center of Jiuting Community Health Service Center, Songjiang District, Shanghai City from July 2021 to December 2022 were selected by a cross-sectional study with multi-stage sampling method. Questionnaire survey, blood test and bone mineral density (BMD) test were conducted.The differences in all the parameters among the elderly with different bone mass level were analyzed using t-test, chi-square test, binary logistic regression was used to screen the potential risk factors of OP.The results showed that the prevalence of OP in the elderly aged≥60 years old in Jiuting Town was 45.89%.The prevalence of OP increased gradually with the advanced age. The prevalence rate of male was significantly lower than that of female( χ2=211.94, P<0.01).Single factor analysis showed that Dairy products( χ2=9.01, P<0.05), taking calcium( χ2=42.88, P<0.05), physical exercise( χ2=24.73, P<0.05), exercise time( χ2=76.40, P<0.05) and sun exposure( χ2=55.71, P<0.05) were the protective factors for osteoporosis. Multifactor analysis showed that female( wald χ 2=71.46, P<0.001) were the risk factors for osteoporosis. The age of the osteoporosis group was older than that of the non-osteoporosis group [osteoporosis group (72.47±6.89) years old, non-osteoporosis group (68.73±6.34) years old, and the difference was statistically significant, t=-11.67, P<0.05]. The waist circumference, alanine aminotransferase (ALT), creatinine (CR), blood urea nitrogen (BUN) and uric acid (UA) in the non-osteoporosis group were higher than those in the osteoporosis group, and the difference was statistically significant (all P<0.05). The levels of high-density lipoprotein (HDL)[osteoporosis group (1.34±0.35) mol/L, non-osteoporosis group (1.41±0.35) mol/L, t=-4.51, P<0.05] and alkaline phosphatase (ALP)[osteoporosis group (88.46±25.65) mol/L, osteoporosis group (94.56±32.32) mol/L, t=-4.79, P<0.05] in the osteoporosis group were lower than those in the non-osteoporosis group.Low awareness of the knowledge of osteoporosis risk factors(smoking, drinking coffee, high salt and drinking alcohol are 47.28%, 24.15%, 47.79% and 44.90%, respectively), diagnosis and treatment(The symptoms, prognosis, screening methods, medication time and follow-up screening time of osteoporosis were 26.87%, 17.88%, 21.77%, 6.65% and 15.99%, respectivel) and prevention(exercise mode, high calcium food, optimal age of calcium supplementation, the effect of vitamin D on OP, and the appropriate amount of milk to prevent osteoporosis were 33.16%, 42.01%, 13.27%, 12.07%, 9.01%, respectively) were in Jiuting Town. In conclusion, the prevalent rate of OP in the elderly ≥60 years old in Jiuting Town is 45.89%.The main risk factors are female and advanced age. Drinking tea, dairy products, combination of meat and vegetable, taking calcium, physical exercise and sun exposure were the protective factors for osteoporosis. The awareness rate of osteoporosis related knowledge is low, and health education should be strengthened in order to control and prevent the occurrence and development of osteoporosis.

To explore the prevalence and related risk factors of osteoporosis (OP) in the elderly ≥60 years old in Jiuting Town, Songjiang District, Shanghai City. A total of 2 175 local residents aged ≥60 years old who participated in the questionnaire survey at the physical examination center of Jiuting Community Health Service Center, Songjiang District, Shanghai City from July 2021 to December 2022 were selected by a cross-sectional study with multi-stage sampling method. Questionnaire survey, blood test and bone mineral density (BMD) test were conducted.The differences in all the parameters among the elderly with different bone mass level were analyzed using t-test, chi-square test, binary logistic regression was used to screen the potential risk factors of OP.The results showed that the prevalence of OP in the elderly aged≥60 years old in Jiuting Town was 45.89%.The prevalence of OP increased gradually with the advanced age. The prevalence rate of male was significantly lower than that of female( χ2=211.94, P<0.01).Single factor analysis showed that Dairy products( χ2=9.01, P<0.05), taking calcium( χ2=42.88, P<0.05), physical exercise( χ2=24.73, P<0.05), exercise time( χ2=76.40, P<0.05) and sun exposure( χ2=55.71, P<0.05) were the protective factors for osteoporosis. Multifactor analysis showed that female( wald χ 2=71.46, P<0.001) were the risk factors for osteoporosis. The age of the osteoporosis group was older than that of the non-osteoporosis group [osteoporosis group (72.47±6.89) years old, non-osteoporosis group (68.73±6.34) years old, and the difference was statistically significant, t=-11.67, P<0.05]. The waist circumference, alanine aminotransferase (ALT), creatinine (CR), blood urea nitrogen (BUN) and uric acid (UA) in the non-osteoporosis group were higher than those in the osteoporosis group, and the difference was statistically significant (all P<0.05). The levels of high-density lipoprotein (HDL)[osteoporosis group (1.34±0.35) mol/L, non-osteoporosis group (1.41±0.35) mol/L, t=-4.51, P<0.05] and alkaline phosphatase (ALP)[osteoporosis group (88.46±25.65) mol/L, osteoporosis group (94.56±32.32) mol/L, t=-4.79, P<0.05] in the osteoporosis group were lower than those in the non-osteoporosis group.Low awareness of the knowledge of osteoporosis risk factors(smoking, drinking coffee, high salt and drinking alcohol are 47.28%, 24.15%, 47.79% and 44.90%, respectively), diagnosis and treatment(The symptoms, prognosis, screening methods, medication time and follow-up screening time of osteoporosis were 26.87%, 17.88%, 21.77%, 6.65% and 15.99%, respectivel) and prevention(exercise mode, high calcium food, optimal age of calcium supplementation, the effect of vitamin D on OP, and the appropriate amount of milk to prevent osteoporosis were 33.16%, 42.01%, 13.27%, 12.07%, 9.01%, respectively) were in Jiuting Town. In conclusion, the prevalent rate of OP in the elderly ≥60 years old in Jiuting Town is 45.89%.The main risk factors are female and advanced age. Drinking tea, dairy products, combination of meat and vegetable, taking calcium, physical exercise and sun exposure were the protective factors for osteoporosis. The awareness rate of osteoporosis related knowledge is low, and health education should be strengthened in order to control and prevent the occurrence and development of osteoporosis.

Purpose To construct the model of differentiating primary central nervous system lymphoma(PCNSL)and atypical glioblastoma(GBM)by combining multi-parameter MRI radiomics and six machine learning algorithms,thus to compare the diagnostic efficacy of different machine learning algorithms.Materials and Methods The clinical and imaging data of 77(125 lesions)PCNSL and 90 atypical GBM(108 lesions)from PLA General Hospital and public databases were retrospectively analyzed from January 2013 to December 2023,and all patients were randomly divided into a training set(163 cases)and a validation set(70 cases)according to 7∶3.T1WI,T2WI and T1-weighted contrast-enhanced sequences were selected for tumor segmentation,and 1 132 radiomics features were extracted from each region of interest.The intraclass correlation coefficient(ICC)was used for the consistency test,and image features with ICC≥0.85 were selected.ICC and recursive feature elimination were used to select the best radiomics features.Six classifiers were used to train and verify three single sequence feature sets,three double-sequence sets and one multi-sequence set.The receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the model.Results The combination model of the support vector machine of radial basis function classifier and multi-sequence feature set were the best model for differentiating PCNSL and atypical GBM.The area under the curve of the training set and the validation set were 0.969 and 0.913,respectively;and the accuracy were both 0.886.Conclusion Noninvasive extraction of multiparametric MRI features combined with machine learning algorithms can effectively differentiate PCNSL and atypical GBM,which provides support for the development of individualized treatment plans for patients.

Objective:To develop a limb function exercise program for patients on extracorporeal membrane oxygenation (ECMO) and provide theoretical guidance for clinical nursing staff.Methods:A research team was formed to systematically review domestic and international literature on functional exercise for ECMO patients, extracting relevant evidence to form the initial version of the limb function exercise program. From June to July 2023, the Delphi method was used to conduct two rounds of expert consultations with 18 experts from three provinces and municipalities directly under the central government, including Shanghai, Jiangsu, and Shanxi. Based on the experts' feedback, the program items were revised to form the final version of the exercise program.Results:In the first round, 18 experts were consulted, with a valid response rate of 94.44% (17/18); in the second round, 17 experts participated, with a 100.00% (17/17) response rate. The expert authority coefficient was 0.859 in both rounds. The coefficient of variation for each level of indicator in the second round ranged from 0 to 0.160, and Kendall's coefficient of concordance was 0.092 to 0.130 ( P<0.01). The final ECMO patient limb function exercise program consisted of four primary indicators (preparation, assessment, exercise methods, and safety monitoring), 13 secondary indicators, and 44 tertiary indicators. Conclusions:The ECMO patient limb function exercise program developed in this study is scientifically sound and reliable, offering a reference and guidance for the implementation of limb function exercises for ECMO patients.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.