Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.
Rats ; Animals ; Myocytes, Cardiac ; Atrial Remodeling ; Rats, Sprague-Dawley ; Heart Failure/metabolism* ; RNA, Messenger/metabolism* ; Potassium

Aim To explore the potential targets and mechanisms of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease. Methods Firstly, TCMSP database, disease database and compound target prediction platform were used to collect active components, disease targets and predict potential targets. Secondly, Cytoscape 3.7.2 and String platform were used to screen key chemical components and core targets, and PPI network diagram was constructed. Finally, The active components with degree greater than 30 were used for molecular docking with key targets, and some docking results were selected for cell experiment. Results The key active components of Houpuwenzhongtang in the treatment of spleen and stomach deficiency cold stomach disease were hesperidin, magnolol, 6-gingerol, and so on. The key targets were JUN, AKT1, IL-8, etc.. The related pathways mainly involved immune response, signaling transduction, cell proliferation and apoptosis. Molecular docking results showed that the key active components had good binding activity with disease targets. The results of cell experiments showed that magnolol, hesperidin and 6-gingerol had different degrees of anti-inflammatory activity against IL-8 in a dose-dependent manner. Conclusions It is speculated that Houpuwenzhongtang may act on IL-8, JUN, AKT1 and other targets through magnolol, hesperidin,6-gingerol and other active ingredients, and participate in the regulation of PI3K-AKT signaling pathway, N F-K B signaling pathway for the treatment of spleen and stomach deficiency cold stomach disease. And it is found for the first time that 6-gingerol could stably bind to multiple disease targets related spleen and stomach deficiency cold stomach disease,such as AKT1,IL-8 and so on. The result suggests that 6-gingerol is worth further research. Through the results of IL-8 cell experiment, it is speculated that the components such as magnolol and hesperidin may play a role in gastric diseases caused by Helicobacter pylori infection by reducing the content of IL-8 in gastric mucosa.

Objective To investigate the changes in plasma amyloid-β (Aβ) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aβ42 and Aβ40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aβ42,Aβ40,and Aβ42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aβ42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aβ42 level showed no significant difference among the three groups (P=0.227).The plasma Aβ40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aβ42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aβ42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aβ42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aβ42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aβ levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aβ levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.
Humans ; Diffusion Tensor Imaging ; White Matter/diagnostic imaging* ; Cognitive Dysfunction ; Outpatients ; Cognition ; Amyloid beta-Peptides

Vaccination is an effective way to reduce the morbidity and mortality of infectious diseases. As a needle-free transcutaneous immunization (NF-TCI) vaccination technology, microneedles (MNs), composed of multiple micro-needles orderly attached to a substrate, can overcome the problems of low immune efficiency, poor compliance and waste of resources that exists in the conventional vaccination by injection, thus becoming a research hotspot in biomedicine. The microneedle vaccine can directly break through the stratum corneum barrier of the skin without touching nerves and blood vessels in the dermis, and effectively delivers the vaccine to the immune cells in the skin tissue to initiate the immune response of the body, thus triggering strong humoral and cellular immune processes. Vaccine delivery via the MNs system possesses the advantages of high safety, satisfying immune effect and practical economy, and shows great prospect in the prevention and treatment of infectious diseases and antineoplastic therapy. This article reviews the development background of MNs in transcutaneous immunization, the types of vaccine delivery, the factors affecting the immune effect, the problems to be solved and development direction in the future.

Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC). Methods: In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A. Results: RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells. Conclusion Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.
Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Hexokinase/metabolism* ; Humans ; Liver Neoplasms/pathology* ; Protein Phosphatase 2/metabolism* ; RNA, Small Interfering/metabolism*

OBJECTIVE: To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. METHODS: Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. RESULT: Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01). CONCLUSIONS The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

To explore the optimal therapy time for the treatment of severe coronavirus disease 2019(COVID-19)by traditional Chinese medicine(TCM)and its influence on the therapeutic effect and prognosis. The clinical data,laboratory findings,and outcomes of 64 patients with severe COVID-19 treated with TCM and western medicine in Chongqing from January 20,2020, to March 11,2020 were retrospectively analyzed.Patients were divided into early intervention group[TCM was initiated within 3 days (including day 3) after the first diagnosis of severe type/critical type COVID-19]and late intervention group[TCM was initiated after 7 days (including day 7) after the first diagnosis of severe type /critical type COVID-19].The changes in clinical parameters during the course of disease were compared between the two groups. On day 14,the oxygenation index was 292.5(252.0,351.0)mmHg in the early intervention group,which was significantly higher than that in the late intervention group [246.0(170.0,292.5)mmHg](=0.005).The length of hospital stay [(18.56±1.11)d (24.87±1.64)d,=0.001],duration of ICU stay [(14.12±0.91)d (20.00±1.53)d,=0.000] and time to negativity [(16.77±1.04)d (22.48±1.66)d,=0.001] in the early intervention group were significantly shorter than those in the late intervention group.The intubation rate(7.3%)in the early intervention group was significantly lower than that in the late intervention group(30.4%)(=0.028). Early TCM therapy within three days after a diagnosis of severe COVID-19 can shorten the length of hospital stay,duration of ICU stay,and time to negativity and decrease intubation rate.
Betacoronavirus ; Coronavirus Infections ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prognosis ; Retrospective Studies

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To explore the ultrastructure characteristics of patients with dampness-heat of Pi (Spleen)-Wei (Stomach) syndrome (DHPW) and Pi-qi deficiency syndrome (PQD), both of which are Helicobacter pylori (Hp)-correlated gastric diseases (HPCG), and implicate a helpful hint for the clinical microcosmic syndrome differentiation. METHODS: Fourteen gastric mucosa samples from 6 chronic gastritis (CG) and 6 active peptic ulcer (including 8 DHPW, 4 PQD) as well as 2 healthy volunteers were collected and tested for Hp infection. The ultrastructure of gastric mucosa was observed under the transmission electron microscope (TEM). RESULTS: Among 14 gastric mucosa samples, 8 of them were Hp positive (6 DHPW and 2 PQD), which were all accordance with the results screened by supermicro-pathological method. Under TEM, the normal gastric mucosa, with tidy microvilli and abundant in mucus granules, mitochondria and rough endoplasmic reticulum distributed evenly, and with smooth nucleus membrane. But in those specimens of DHPW with Hp infection, microvilli were presented with burr shape. Especially, those samples from dampness-heat syndrome with predominant heat type (DHSH) patients were more obvious, with microvilli damaged, mitochondria concentrated and distributed in disorder, secretory tubule extended. In dampness-heat syndrome with predominant dampness type (DHSD) patients, mucus granules aggregated obviously, mitochondria swelled and blurred, and rough endoplasmic reticulum crowded. For 2 samples of DHPW without Hp infection, their microvilli were intact, with mitochondria increased and gathered but well-distributed, and secretory tubule extended mildly. In 2 PQD patients with Hp positive, the specimens of microvilli were sparse, and their mucus granules and mitochondria were decreased, with fractured crests and vacuole, secretory tubules extension to nucleus membrane, and rough endoplasmic reticulum extension in a pool-like way, and nucleus condensed. The 2 samples from PQD patients without Hp infection were characterized with intact microvilli, decreased mitochondria, fractured crest and extended rough endoplasmic reticulum in a pool-like way. CONCLUSION It's obviously different in ultrastructure of DHPW and PQD patients under TEM, which may give a helpful hint for the microcosmic syndrome differentiation of HPCG.