OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.

Cardiac cephalalgia is a rare disease caused by underlying coronary artery disease that presents as headache with or without chest symptoms.Headache symptoms are often caused by referred pain,increased intracranial pressure and release of large amounts of pain-causing neurochemicals due to myocardial ischemia,and cortical hypoperfusion.Due to the low overall prevalence of the disease,the lack of chest pain typical of coronary heart disease,and the fact that it may be difficult to distinguish from headaches caused by neurological diseases,accurate diagnosis and treatment of the disease are often delayed.We report a case of acute coronary syndrome with headache only.Revascularization was achieved through percutaneous coronary intervention therapy,followed by standard secondary prevention pharmacotherapy.Follow-up six months postoperatively showed a significant improvement in exercise tolerance,with no further headache episodes.The purpose is to improve the understanding of patients with cardiac cephalalgia,with a view to early identification and timely intervention,and ultimately improve the symptoms and prognosis.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective To observe the therapeutic efficacy and mechanism of Gushi Zaizao Pills for steroid-induced osteonecrosis of the femoral head(SONFH).Methods Male SD rats were randomly divided into normal group,model group,Xianling Gubao Capsules group and Gushi Zaizao Pills group.Except for the normal group,the rats in all other groups were replicated the SONFH model.After successful modeling,the continuous drug administration was carried out for six weeks.The thymus and spleen of the rats were taken to calculate the immune organ indices,the contents of interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)in rat synovial fluid were detected by enzyme-linked immunosorbent assay(ELISA),the percentage of empty lacunae and area ratio of trabecular bone was detected by hematoxylin-eosin(HE)staining,and the femoral head parameters[reduction of bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th)and trabecular separation(Tb.Sp)]were analyzed by Micro-CT,and bone strength of femoral head was detected by small animal bone strength tester.Results Compared with the normal group,the spleen and thymus indicators were significantly decreased in the model group,the levels of IL-1β and TNF-α in rat synovial fluid were significantly increased,the percentage of empty lacunae was increased,the area ratio of trabecular bone was decreased,the BV/TV,Tb.N and Tb.Th were decreased,the Tb.Sp was increased,the bone strength of femoral head was significantly decreased,the differences being all statistically significant(P＜0.05 or P＜0.01).Compared with the model group,the spleen and thymus indicators were significantly increased in Xianling Gubao Capsules group and Gushi Zaizao Pills group,the levels of IL-1β and TNF-α in rat synovial fluid were decreased,the percentage of empty lacunae was significantly decreased,the area ratio of trabecular bone was significantly increased,the BV/TV,Tb.N and Tb.Th were increased,the Tb.Sp was decreased,and the bone strength of femoral head was significantly increased,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Gushi Zaizao Pills can effectively prevent the further development of SONFH by regulating cellular immunity and reducing the secretion of inflammatory factors,thereby reducing the pathological damage of the femoral head and enhancing the bone strength.

Aim To investigate the effect of XNST and its monomeric components on the barrier structure and tight junction protein expression of brain microvascular endothelial cells damaged by oxygen glucose deprivation/reoxygenation (OGD/R) and the possible mechanism. Methods The mouse brain microvascular endothelial cell line bEnd. 3 was inoculated in the upper layer of the Transwell chamber to establish an OGD/R damage model, and the effect of the drug on the integrity of the endothelial cell barrier was investigated by the transmembrane resistance value and fluorescein-so-dium transmittance. Claudin-5 immunofluorescence staining was used to observe the changes of tight junction structure between endothelial cells. RT-PCR and Western blot were employed to detect mRNA and protein expression levels of tightly linked proteins Claudin-5 , Occludin, ZO-1. Western blot was applied to detect the expression levels of MAPKs (JNK, p38, ERK) , I kappa B a, I kappa B kinase phosphorylated protein expression, and Western blot and immunofluorescence were utilized to detect NF-K.B/p65 nucleation expression. Results XNST and its three monomers could significantly increase endothelial cell resistance and de- crease fluorescein-sodium transmittance. Claudin-5 fluorescence staining showed that the tight junction between cells in the model group was significantly damaged , while XNST and its monomer components could significantly improve its tight structure. RT-PCR and Western blot results showed that it could significantly upregulate the expression of mRNA and protein of Claudin-5, Occludin and ZO-1, and further study on the mechanism showed that XNST and its monomer components could significantly inhibit the phosphoryla-tion of JNK, p38 and ERK, inhibit the phosphorylation of I kappa B a and I kappa B kinases, and significantly inhibit the nuclear translocation of NF-KB/p65. Conclusion Both XNST and its monomeric components can exert cerebroprotective effects by increasing the tight junction structure between cells to promote barrier integrity, and the mechanism may be related to inhibition of NF-kB and MAPKs signaling pathway activation.

The fenrou zhijian is defined as potential gap between different layers in the three-dimensional network structure formed by the twelve meridian tendons. Various pathological changes of the meridian tendons lead to the adhesion and closure of fenrou zhijian, causing abnormal mechanical conduction of the meridian tendon system, which in turn leads to painful bi syndrome of meridian tendons. As such, restarting the fenrou zhijian is the key to acupuncture treatment for painful bi syndrome of meridian tendons. Under the guidance of musculoskeletal ultrasound, the level and the angle of needle insertion of acupuncture at fenrou zhijian could be accurately controlled, the efficacy of acupuncture is improved.
Humans ; Meridians ; Acupuncture Therapy ; Needles ; Pain ; Tendons/diagnostic imaging*

OBJECTIVE: The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population. METHODS: From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria. RESULTS: During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01). CONCLUSION NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.
Adult ; Aged ; Ankle Brachial Index ; Body Mass Index ; China/epidemiology* ; Cohort Studies ; Female ; Humans ; Incidence ; Lymphocytes/cytology* ; Male ; Middle Aged ; Neutrophils/cytology* ; Poisson Distribution ; Prospective Studies ; Vascular Diseases/etiology*