Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

Objective: To elucidate the biological basis of the heart qi deficiency (HQD) pattern, an in-depth understanding of which is essential for improving clinical herbal therapy. Methods: We predicted and characterized HQD pattern genes using the new strategy, TCM-HIN2Vec, which involves heterogeneous network embedding and transcriptomic experiments. First, a heterogeneous network of traditional Chinese medicine (TCM) patterns was constructed using public databases. Next, we predicted HQD pattern genes using a heterogeneous network-embedding algorithm. We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq. Finally, we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis. Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism, signal transduction pathways, and immune processes. Moreover, we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern. Furthermore, herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD. Conclusion Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes, but also deciphering the basis of HQD pattern. Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns, leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.

Objective:To summarize and elucidate the impact of ambient air pollution on biological aging among middle-aged and older adults.Methods:"Air pollution""Biological age""Epigenetic age""Biological aging"and"Epigenetic aging", as well as specific names of air pollutants and biological age were used as search keywords. This study searched the databases of PubMed and Web of Science for eligible English articles and CNKI, CQVIP, Wanfang, CBM, CSTP and other Chinese databases for eligible Chinese articles from inception until June 30, 2023. The language was limited to Chinese and English.Results:Among the 14 included articles, five studies investigated the impact of air pollution on DNA methylation age using different algorithms, while six studies explored the relationship between air pollutants and telomere length. Six studies focused on frailty as an outcome, and an additional study revealed the relationship between fine particulate matter (PM 2.5) and its components with composite indicator age (KDM age). The results indicated that, although different forms of biological ages were susceptible to different ambient air pollutants at different degrees, previous studies had consistently found that the increased levels of PM 2.5 and one of its major components, black carbon (BC), could significantly accelerate the biological aging of middle-aged and older adults. Similar trends were observed with nitrogen oxides (NO x) and ozone (O 3) but with relatively limited evidence. Conclusion:Major air pollutants could accelerate the biological aging of middle-aged and older adults.

Objective To explore the enrichment method of the crude alkaloid of Zanthoxylum nitidum(Roxb.)DC.(Z.nitidum),which can inhibit the proliferative activity of human erythroid leukemia cells(HEL cells)in vitro,and to provide a scientific basis for the antitumor activity of Z.nitidum.Methods Z.nitidum was extracted using different concentrations of ethanol(60%,70%,80%,90%,and 100%)to determine the optimum extraction conditions according to the highest extraction rate.Static and dynamic adsorption determined the adsorption capacity of different macroporous resins(HPD 100,XDA-5,D101,HPD 722,HPD 400)on the ethanol extracts from Z.nitidum.The effects of crude alkaloids on the proliferation activity of HEL cells in each group were studied by the MTT method.Results Z.nitidum was extracted from 60%,70%,80%,90%,and 100%ethanol,and the extract with 60%ethanol concentration had the highest yield(11.937±0.002)%.Static and dynamic adsorption experiments showed that the adsorption capacity of the above five kinds of macroporous resins was 1∶500(extract of Z.nitidum∶macroporous resin).The crude alkaloids enriched by different macroporous resins have different effects on the proliferation activity of HEL cells.The inhibition rates(%)at a concentration of 80 μg·mL-1 of Z.nitidum were(59.62±3.46)%(XDA-5),(55.81±5.16)%(HPD 100),(59.33±1.33)%(D101),(79.63±1.02)%(HPD 722),and(83.97±0.38)%(HPD 400),respectively.HPD 400 macroporous resin-enriched crude alkaloids inhibited the proliferation of HEL cells most significantly(P<0.01).Conclusion The process of enriching the crude alkaloids of Z.nitidum using macroporous resin was simple and feasible,and the crude alkaloids enriched by HPD 400 showed significant inhibitory effects on HEL cells with good anti-leukemic activity.

Objective:To summarize and elucidate the impact of ambient air pollution on biological aging among middle-aged and older adults.Methods:"Air pollution""Biological age""Epigenetic age""Biological aging"and"Epigenetic aging", as well as specific names of air pollutants and biological age were used as search keywords. This study searched the databases of PubMed and Web of Science for eligible English articles and CNKI, CQVIP, Wanfang, CBM, CSTP and other Chinese databases for eligible Chinese articles from inception until June 30, 2023. The language was limited to Chinese and English.Results:Among the 14 included articles, five studies investigated the impact of air pollution on DNA methylation age using different algorithms, while six studies explored the relationship between air pollutants and telomere length. Six studies focused on frailty as an outcome, and an additional study revealed the relationship between fine particulate matter (PM 2.5) and its components with composite indicator age (KDM age). The results indicated that, although different forms of biological ages were susceptible to different ambient air pollutants at different degrees, previous studies had consistently found that the increased levels of PM 2.5 and one of its major components, black carbon (BC), could significantly accelerate the biological aging of middle-aged and older adults. Similar trends were observed with nitrogen oxides (NO x) and ozone (O 3) but with relatively limited evidence. Conclusion:Major air pollutants could accelerate the biological aging of middle-aged and older adults.

ObjectiveTo establish and evaluate a mouse model of heart failure with Qi deficiency syndrome. MethodForty-four KM mice were randomly divided into sham operation group， model group， and modified Si Junzitang group （12.89 g·kg^-1）. The model group and the modified Si Junzitang group underwent thoracic aortic constriction （TAC）， while the sham operation group only underwent suture without constriction. Echocardiography and pathological examination were used to assess the heart failure model and evaluate the pharmacological effects. Macroscopic characterization， microscopic biology， and formula identification were conducted to collect general signs， body weight， open-field behavior， grip strength， mitochondrial ultrastructure， and other macroscopic and microscopic characteristics of mice. Mitochondrial fission and fusion protein expression were measured to determine the syndrome type. ResultEight weeks after TAC， compared with the sham operation group， the model group showed a significant decrease in left ventricular ejection fraction （LVEF） （P<0.01）， and modified Si Junzitang improved LVEF in mice （P<0.05）. Hematoxylin-eosin （HE） staining of the heart showed inflammatory cell infiltration and thickening of blood vessel walls in the model group， which was significantly improved by modified Si Junzitang. After 6-8 weeks， compared with the sham operation group and the modified Si Junzitang group， the model group exhibited significant hair loss， hair yellowing， decreased activity， and depression. Moreover， compared with the sham operation group， the model group had a significantly lower increase in body weight （P<0.05）， while the modified Si Junzitang group showed a significant increase in body weight （P<0.05） compared with the model group. After 6-8 weeks， compared with the sham operation group， the model group showed a significant decrease in open-field distance and speed （P<0.05）， while the modified Si Junzitang group exhibited significantly improved open-field distance and speed in the 8^th week （P<0.05）. After 6-8 weeks， compared with the sham operation group， the model group exhibited a significant decrease in maximum grip strength （P<0.05）， while the modified Si Junzitang group showed a significant increase in maximum grip strength 8 weeks after TAC （P<0.05）. Transmission electron microscopy of the gastrocnemius muscle showed uneven muscle tissue matrix， mitochondrial swelling， increased volume， matrix dissolution， ridge loss， and vacuolization in the model group， while modified Si Junzitang improved mitochondrial swelling， ridge fracture， and matrix vacuolization. Western blot analysis showed that the expression of the kinetic associated protein 1 （DRP1） in the gastrocnemius muscle of the model group significantly increased （P<0.01）， and the expression of mitochondrial fusion hormone 1 （MFN1） significantly decreased （P<0.05） as compared with those in the sham operation group. Furthermore， compared with the model group， the modified Si Junzitang group exhibited a significant decrease in the expression of DRP1 （P<0.05） and a significant increase in MFN1 expression （P<0.01）. ConclusionMice exhibited significant manifestations of qi deficiency syndrome 6-8 weeks after TAC， accompanied by abnormal mitochondrial morphology and function in the gastrocnemius muscle， which were significantly improved by modified Si Junzitang.

Objective:To investigate the clinical characters and prognostic value of PSA flare and bone flare in metastatic castration resistant prostate cancer(mCRPC) patients received Abiterone acetate(AA) therapy.Methods:A retrospective study was conducted for 93 mCRPC patients treated with AA from Jul.2016 to Dec.2020. Mean age was (75.4±8.9)years, median PSA was 58.2 (16.4, 148.6)ng/ml. Patients received at least 6 months of AA treatment. PSA flare was defined as an increase of PSA after AA therapy followed by a decrease. Bone flare was defined as disease progression after 3 months of therapy, typically based on increased lesion intensity or number, and reevaluation 6-9 months later showed improvement in the scan. The clinical characters and prognostic value of the flare phenomenon was evaluated and analyzed respectively.Results:The median follow up time was 16 months(6, 54 months), fourteen patients showed PSA flare at first month after AA treatment, and median time of duration was 2 months(1, 7 months). The serum alkaline phosphatase (ALP) had a similar rising trend along with PSA flare[115.5(98.0, 198.5)U/L vs. 119.0(97.0, 288.8)U/L, P=0.016]. Seven patients showed bone flare and 3 cases co-existed with PSA flare. Multivariate Cox regression analysis indicated bone flare was an independent protective factor for progression free survival(PFS)( HR=0.117, 95% CI 0.015-0.895, P=0.039), PSA flare had no significant influence on PFS ( HR=1.314, 95% CI 0.554-3.121, P=0.536)and overall survival(OS)( HR=1.348, 95% CI 0.393-4.263, P=0.635). Log-rank test showed patients with bone flare had a longer PFS( P=0.016) and OS( P=0.047) compared with patients without bone flare. Conclusions:PSA flare always faded away after 2 months AA therapy and had no influence on PFS and OS. Bone flare maybe an indication for better prognosis.

In response to the Opinions of the CPC Central Committee and the State Council on Promoting the Inheritance， Innovation， and Development of traditional Chinese medicine（TCM） and the spirit of the National Conference on TCM， Chinese Association of Chinese Medicine organized experts in Otorhinolaryngology Head and Neck Surgery of traditional Chinese and western medicine to discuss the clinical advantages of TCM and integrated traditional Chinese and western medicine in the treatment of allergic rhinitis （AR） and they reached a basic consensus. In recent years， the prevalence of AR has been on the rise， threatening the quality of life of patients and giving rise to a heavy burden to both the patients and the society. AR is resulted from immune imbalance rather than reduced immunity or hyperimmunity， and the imbalance is similar to the Yin-yang disharmony in TCM. In the treatment of this disease， western medicine features rapid onset. However， it is cost-intensive and causes severe surgical trauma， and the recurrence is common. TCM boasts diverse methods for AR， which can be used in all stages of this disease. It has advantages in controlling symptoms such as nasal congestion， runny nose， or dysosmia in the attack stage， preventing recurrence in the remission stage， and treating refractory AR or steroid-resistant AR. In particular， acupuncture enjoys a reputation in treatment of AR， which has been supported by evidence-based medicine and recommended by guidelines. While treating local symptoms of AR， TCM regulates the psychosomatic conditions， which facilitates chronic disease management and long-term follow-up. We should integrate the advantages of TCM and western medicine， give full play to the unique nonnegligible and irreplaceable advantages of TCM， formulate a comprehensive diagnosis and treatment scheme for learning and promotion， and summarize the research outcomes to promote the theoretical innovation of TCM on AR from the perspective of integrated traditional Chinese and western medicine.

Objective:To investigate outcomes and safety of doxycycline-moxifloxacin sequential regimen in the treatment of Mycoplasma genitalium urethritis/cervicitis. Methods:From June 2019 to December 2020, patients with Mycoplasma genitalium urethritis/cervicitis confirmed by nucleic acid amplification testing were successively recruited at Department of Sexually Transmitted Diseases, Hospital of Dermatology, Chinese Academy of Medical Sciences, and received sequential therapy with oral doxycycline for 7 days followed by oral moxifloxacin for 7 days. Clinical and/or etiological assessment was conducted 2 to 3 weeks after the end of treatment. Fisher′s exact test was used to analyze factors influencing the treatment outcome. Results:Totally, 36 eligible subjects were enrolled, including 30 males and 6 females. Among them, 18 (50%) patients completed post-treatment etiological assessment, which showed that 12 achieved microbiological cure, and treatment failures occurred in 6; another 18 patients achieved clinical cure. The overall response rate to doxycycline-moxifloacin sequential therapy was 83.3% (30/36, 95% confidence interval[ CI]: 70.5%, 96.1%) . The treatment outcome showed no significant association with the patients′ age, gender, marital status, number of sexual partners in the past 1 month, history of sexually transmitted diseases, history of antibiotic use in the past 1 month, or co-infections (all P > 0.05) . Conclusion:The efficacy of doxycycline-moxifloacin sequential regimen is limited in the treatment of Mycoplasma genitalium infections in Nanjing area, and clinicians should be alerted to the possibility of treatment failure in clinical practice.

ObjectiveTo explore the effect of sweroside on the protection of cardiac systolic/diastolic function during ischemia/reperfusion （I/R） injury. MethodTwenty-four healthy male SD rats were randomly divided into control group， model group， 10 μmol·L^-1 sweroside group and 1 μmol·L^-1 digoxin group. The I/R injury was modeled by Langendorff and ligation of the left anterior descending coronary artery. The infarct size in each group was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining and hemodynamic parameters such as left ventricular diastolic pressure （LVDP）， left ventricular end-diastolic pressure （LVEDP）， left ventricular end-systolic pressure （LVESP）， maximum rate of rising of left ventricular pressure （+dp/dt_max） and maximum rate of decreasing of left ventricular pressure （-dp/dt_max） of rat isolated heart were detected by Powerlab. In addition， neonatal rat cardiomyocytes （NRCMs） were isolated and randomly divided into control group， model group， 1 μmol·L^-1 sweroside group and 10 μmol·L^-1 sweroside group. Hypoxia/reoxygenation （H/R） injury model was established. Cardiac systolic function and calcium transients were examined by multi-functional cell imaging analyzer and laser confocal microscope. Furthermore， real-time polymerase chain reaction（Real-time PCR） was used to verify the mRNA expression of excitation-contraction coupling genes such as L-type calcium channel （Cacnb2）， cytochrome c oxidase subunit 6A2 （Cox6a2）， troponin （Tnnc1， Tnni3， Tnnt2）， actin （Actc1）， and myosin （Myh6， Myl2， Myl4） according to the results of previous transcriptome sequencing and literature investigation. Differentially expressed genes were subjected to cluster analysis. ResultCompared with the conditions in the control group， increased cardiac infarction size （P<0.01） and LVEDP （P<0.01） and decreased LVDP （P<0.01） and LVESP （P<0.05） were observed in the model group， with +dp/dt_max of increasing trend while -dp/dt_max decreasing. Moreover， the cell viability， heart rate and contraction amplitude of NRCMs was reduced （P<0.01）， while the contraction duration， time to peak and relaxation time was elevated （P<0.01） in the model group. Interestingly， sweroside could reverse these indicators （P<0.05）. In addition， the expression of Cacnb2， Cox6a2， Tnnc1， Tnni3， Tnnt2， Actc1， and Myh6， Myl2， and Myl4 was down-regulated in the model group （P<0.05， P<0.01）， but sweroside could up-regulate the expression of the above genes （P<0.05）. ConclusionSweroside effectively regulated Ca²⁺ level in NRCMs， enhanced cardiac systolic function， and protected against H/R injury by regulating excitation-contraction coupling.