ObjectiveTo observe the effects of Yuejuwan in the treatment of psychological and heart diseases （PHD） and explore its mechanism. MethodThirty 6-week-old healthy male SPF AopE^-/- mice and 10 homologous C57BL/6J mice were selected for the experiment. The 30 AopE^-/- mice were divided into a model group， low-dose （7.58 g·kg^-1·d^-1） and high-dose （30.32 g·kg^-1·d^-1） Yuejuwan groups， with 10 mice in each group， and 10 C57BL/6J mice were assigned to the blank control group. Intragastrical administration lasted 12 weeks. During feeding， the PHD model was induced by chronic unpredictable mild stress （CUMS） combined with high-fat diet in mice. After intragastric administration， the behavioral results ［open field test （OFT） and sucrose preference test （SPT）］ of mice in each group， the content of aspartic transaminase （AST）， alanine aminotransferase （ALT）， 5-hydroxytryptamine （5-HT）， noradrenaline （NE）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， total cholesterol （TC）， and triglyceride （TG） in serum of mice detected by the automatic biochemical analyzer， the oil red O staining and HE staining of aorta and liver and Masson staining of myocardial tissues were used for model evaluation. Finally， liver TMT-labeled quantitative proteomics was used to explore the mechanism of action. ResultThe model mice showed obvious manifestations of depression， anxiety， loss of interest， and despair， manifest lipid deposition in the aorta and liver by pathological observation， and increased myocardial fibrosis in myocardial tissues. After intragastric administration of Yuejuwan， the above symptoms and indexes of the PHD model mice were improved. Compared with the blank control group， the model group showed decreased standing times， cumulative time in the central area， total moving distance， moving speed， and sucrose preference at week 12 （P<0.01）. Compared with the model group， the Yuejuwan groups showed decreased indexes mentioned above （P<0.01）. After sample collection， AST， ALT， and TG levels in the model group were higher （P<0.01） and the levels of 5-HT， NE， and HDL-C were lower than those in the blank control group （P<0.01）. The results of liver TMT labeled quantitative proteomics suggested that the PHD model mainly caused the changes in protein expression levels such as ApoE， UGT1A5， and FASN in mice，involving acetyl CoA metabolism，response to bacteria，cellular amino acid catabolism， and other processes，which were related to the abnormal metabolic function of the liver. The efficacy of Yuejuwan against PHD was achieved mainly through the regulation of high mobility group nucleosomal-binding domain 2 （HMGN2）， CALD1， and Mup7 protein expression levels and correcting the biological processes and abnormal pathways related to the pathogenesis of PHD，including muscle contraction，tight junction pathway，myocardial contraction pathway，and focal adhesion pathway. ConclusionCUMS combined with high-fat diet is reasonable in the induction of the PHD model in AopE^-/- mice. Yuejuwan can correct the depression and anxiety conditions of PHD model mice，reduce the aortic plaque， and recover the abnormal blood lipid and liver function levels. Furthermore， Yuejuwan can correct abnormal biological processes and pathways of PHD model mice. The differential proteins screened throughout the experiment and the involved physiological and pathological changes are the focus of the next experiment.

Abstract: Objective To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Ankang City from 2011 to 2021, so as to provide a scientific basis for the formulation of PTB prevention and control strategy. Methods Descriptive statistics were used to analyze the epidemiological characteristics of PTB in Ankang City from 2011 to 2021, and a time series model was established to quantitatively predict the incidence of pulmonary tuberculosis in 2023. Results The incidence rate in Ankang City showed a significant upward trend from 2011 to 2017, and a more obvious downward trend in 2017-2021 (P<0.05), and the decrease rate in 2021 was 40.36% compared with that in 2017. The proportion of etiological positivity increased from 12.5% in 2014 to over 50.00% after 2019. The incidence season was mainly concentrated in the first quarter, accounting for 28.39% of the annual incidence. High incidence areas were concentrated in the south of Ankang: Langao County, Ziyang County and Zhenping County, with 128.32/100 000, 117.07/100 000 and 110.44/100 000, respectively. Low incidence areas were located in the north of Ankang: Ningshan County, with 60.62/100 000. Farmers and students were the high incidence groups, accounting for 81.80% and 4.97% of the total cases respectively. The incidence of young children was relatively low, but cases were reported every year. The incidence rate of male was 2.39 times that of female. The age of onset increased significantly from 15 years old, and the peak incidence was in the age group of 60-<80 years old, followed by the age group of 45-<60 years old, the average annual incidence was 136.44/100 000 and 104.47/100 000, respectively. The model ARIMA(0,1,1)(0,1,1)12 predicted that the incidence of the disease generally increased from October 2022 to March 2023, then steadily decreased, and increased again in December. Conclusions The incidence of tuberculosis varies in different areas of Ankang City, and males, farmers, students and the elderly are all factors of high incidence of tuberculosis. Therefore, different prevention and control strategies should be adopted according to the characteristics of population in different areas. The number of cases in Ankang City in 2023 showed an overall downward trend, which can provide a reference for the prevention and control of PTB.

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC₅₀) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC₅₀ lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.
Humans ; SARS-CoV-2 ; COVID-19 ; Luteolin ; Quercetin

ObjectiveTo compare the therapeutic effects of oral Chinese medicines （including Chinese patent medicines） on coronary artery disease （CAD） by the Bayesian network Meta-analysis. MethodThe randomized controlled trials of treating CAD with oral Chinese medicines were retrieved from the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， PubMed， Web of Science， Embase， and Cochrane Library from the inception to December 1， 2022. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included articles. The direct meta-analysis was performed to compare the performance of oral Chinese medicines alone and in combination with Western medicine in the treatment of CAD in terms of intima-media thickness （IMT）， vascular endothelial function， plaque score， hypersensitive C-reactive protein （hs-CRP）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and total response rate. Furthermore， the Bayesian network Meta-analysis was performed to compare the therapeutic effects of different Chinese medicines. ResultA total of 41 articles were included. The direct meta-analysis results showed that Chinese medicines combined with Western medicine outperformed Western medicine alone in recovering all the indicators of CAD. The Bayesian network meta-analysis yielded the following results. In terms of the total response rate， modified Huangqi Guizhi Wuwutang and Sanqi Huayu pills had obvious advantages over other Chinese medicines. In terms of IMT and plaque score， Xiaoban Huazhuo decoction， Yiqi Tongluo formula， Ruangan Jiangzhi capsules， and Guanxin Shutong capsules had obvious advantages over other Chinese medicines. In terms of blood lipid indicators， Shenqi Roumai mixture， Ruangan Jiangzhi capsules， Xiaoban Huazhuo decoction， Qiwei Sanxiong decoction， and Sanqi Huayu pills were superior to other Chinese medicines. The Chinese medicines above mainly had the functions of activating blood， resolving stasis， resolving phlegm， and dredging vessels. ConclusionThe combination of oral Chinese medicines and Western medicine is effective in treating CAD. Clinicians can use the drugs targeting abnormal indicators according to the results of this Bayesian network meta-analysis combined with the actual situation of patients to achieve better therapeutic effects.

As a traditional Chinese medicinal material， Glycyrrhizae Radix et Rhizoma has been extensively used in various formulae. According to modern pharmacological research， it has anti-tumor， anti-inflammatory， anti-viral， liver-protecting， anti-heart failure， immunoregulatory， and anti-fibrosis effects. Caused by the interaction of various factors， cancer features complex pathogenesis. It is a global challenge and one of the main causes of death in China. Statistics show that the morbidity and mortality of malignant tumors have been on the rise， particularly for the young， which threaten the health of human beings. At the moment， radiotherapy and chemotherapy are the main countermeasures. Most clinical anti-tumor drugs demonstrate non-selective toxicity. To be specific， they damage normal cells while killing tumor cells， thus injuring vital organs. In addition， long-term medication will reduce the sensitivity of tumor cells. However， traditional Chinese medicine， which is characterized by treatment based on syndrome differentiation， multiple components， and multiple targets， is superior in the treatment of tumor. Studies have shown that the combination of anti-tumor drugs with Chinese medicine can not only enhance the anti-tumor effect but also alleviate toxicity. Therefore， it has been a research hotspot to develop anti-tumor drugs based on traditional Chinese medicine. In recent years， major headway has been made in the research on active ingreddients of Glycyrrhizae Radix et Rhizoma in anti-liver cancer， anti-breast cancer， anti-lung cancer， and anti-colon cancer and the combination with other drugs for anti-tumor. On this basis， we summarized the mechanisms of active ingredients of Glycyrrhizae Radix et Rhizoma in inducing apoptosis， interfering with cell cycle， inducing autophagy， inhibiting glycolysis， regulating immunity， and modulating miRNA and signaling pathways， as well as the combination with other drugs in anti-tumor efficiency， toxicity reduction， and sensitivity enhancement， hoping to lay a theoretical basis for the further development and clinical application of active ingredients of Glycyrrhizae Radix et Rhizoma.

Objective: To investigate the effects of different prescription compositions of traditional Chinese medicine and its different extraction methods of compound formula extracts on hypoxia tolerance in mice, in order to preferably select their prescription compositions and preparation extraction methods. Methods: Male BALB/c mice were randomly divided into 6 groups: blank control group, compound danshen group, compound Rhodiola Rosea alcohol-water extract group (Rhodiola rosea, Astragali Radix, Polygonati Rhizoma, Lycii Fructus), compound Rhodiola Rosea water extract group, compound Astragalus alcohol-water extract group (Astragali Radix, Polygonati Rhizoma, Lycii Fructus) and compound Astragalus water extract group, 30 mice in each group. Each group was administered continuously by gavage for 10 d. The blank group was gavaged with sterilized injection water. The mice in the other groups were treated with 0.15 g/kg of compound danshen, 3 g/kg of compound Rhodiola Rosea alcohol-water extract or water extract, and 1.7 g/kg of compound Astragalus alcohol-water extract or water extract, respectively. Each group was subjected to normobaric hypoxia tolerance test, sodium nitrite toxicity survival test and acute cerebral ischemia-hypoxia test 1 h after the last gavage, and the mice brain tissues were used to determine the activity of antioxidant enzymes and metabolites related to oxidative stress. Results: Compared with the blank control group, in normobaric hypoxia tolerance test, the survival time of mice in the compound danshen group and the compound Astragalus alcohol-water extract group and water extraction group was prolonged significantly (P＜0.01), and the number of open-mouth gasping after cerebral ischemia and hypoxia was increased significantly (P＜0.05). There was no statistical difference in survival time after sodium nitrite injection in each group. Compared with the blank control group, the activities of T-AOC, SOD, GSH and CAT were increased significantly (P＜0.05, P＜0.01) and the content of MDA was decreased significantly (P＜0.01) in the compound Astragalus water extract group. Compared with the compound danshen group, the activities of SOD, CAT and GSH were increased significantly (P＜0.01, P＜0.05) and the content of MDA was decreased significantly (P＜0.05). Conclusion: Compound Astragalus water extraction has the best effect of hypoxia tolerance, compound Rhodiola Rosea can eliminate Rhodiola rosea and consists of Astragali Radix, Polygonati Rhizoma, Lycii Fructus and its extraction method is water extraction.
Animals ; Astragalus Plant ; Ethanol ; Hypoxia ; Male ; Mice ; Plant Extracts/pharmacology* ; Rhodiola ; Sodium Nitrite ; Superoxide Dismutase/metabolism* ; Water

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC₅₀) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC₅₀ lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

Objective: The aging model of guinea pigs induced by D-galactose was set up to investigate the changes of BK_Ca expression and function on cochlear pericytes and their relationship with age-related hearing loss. Methods: Thirty healthy 8-week-old guinea pigs were randomly divided into three groups, with 10 in each group: D-galactose aging model group, subcutaneous injection of D-galactose (500 mg/kg) daily for 6 weeks; saline control group, the same amount of saline was injected into the neck of the aging model group for 6 weeks; the blank control group, no treatment was performed. The threshold of auditory brainstem response (ABR) was detected. The content of BK_Ca in the perivascular cells of the guinea pig cochlear cells was detected by immunofluorescence technique. The changes of peripheral current density and BK_Ca current were detected by patch clamp technique. The data were analyzed by GraphPad Prism software. Results: Compared with the saline group and the control group, the ABR threshold and the amplitude of the wave I were significantly decreased in the aging model group, and the difference was statistically significant (P<0.01). Compared with the control group, the expression of BK_Ca in the vascular pericytes of guinea pigs in the aging model group was significantly reduced (1.00±0.08 vs 0.27±0.03,the difference was statistically significant P<0.01), and the cell current density and BK_Ca net current value were also significantly reduced with statistically significant (P<0.01). Conclusions D-galactose can successfully induce guinea pig aging model, in which BK_Ca expression decreases and net current value decreases in pericytes of cochlear striavascularis, and changes in BK_Ca expression and function may be related to age-related hearing loss.

Objective To explore the efficacy of ganoderma lucidum preparation(Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer's disease(AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/(kg·d)] and middle [750 mg/(kg·d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group(treated with donepezil hydrochloride [2 mg/(kg·d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin(HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared. Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups(hippcampus:F=1.738,P=0.016;dentate nucleus:F=1.924,P=0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups(F=9.46,P=0.007;F=9.46,P=0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD mice and also reduce the amyloid angiopathy.

Objective: To study the chemical constituents of ethyl acetate fraction from Patrinia scabra. Methods: Chemical constituents were isolated and purified by macroporous resin, silica gel, and Sephadex LH-20 column chromatography. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. Results: Twelve compounds were isolated and purified. Their structures were identified as 5-O-feruloylquinic acid (1), 7α-morroniside (2), 7β-morroniside (3), villosol (4), protocatechuic acid (5), β-daucosterol (6), isopatriscabroside I (7), patriscabroside I (8), patrinioside (9), pinoresinol-4,4'-di-O-β-D-glucopyranoside (10), lariciresinol-4'-O-β-D-glucopyranoside (11), and villosolside (12). Conclusion: Compounds 2-6 are isolated from this plant for the first time and the compound 1 is isolated from the plants of Patrinia Juss. (Valerianaceae) for the first time.