Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To explore the difference in the effectiveness between proximal femoral nail anti-rotation(PFNA)and proximal femoral locking compression plate(PFLCP)of intertrochanteric fracture in the elderly patients combined with knee osteoarthritis.Methods The clinical data of 65 intertrochanteric femoral fractures combined with knee osteoarthritis be-tween June 2015 and February 2021 were retrospectively analyze.They were divided into two groups according to the different surgical methods.PFNA group was composed of 36 patients,12 males and 24 females,aged from 61to 88 years old with an av-erage of(77.0±6.4)years old.There were 17 cases of left injury and 19 cases of right injury.According to modified Evans clas-sification,there were 3 cases of type Ⅱ,19 cases of type Ⅲ,10 cases of type Ⅳ,and 4 cases of type Ⅴ.PFLCP group was com-posed of 29 patients,11 males and 18 females,aged from 60 to 92 years old with an average of(78.8±6.5)years old.There were 14 cases of left injury and 15 cases of right injury.According to modified Evans classification,there were 2 cases of typeⅡ,18 cases of type Ⅲ,7 cases of type Ⅳ,and 2 cases of type Ⅴ.Comparison of operation time,intraoperation blood loss,postoperative bed time,incidence of postoperative complications,Harris score at 6 months and 1 year postoperation.Results All 65 patients were followed up ranging from 12 to 24 months with an average of(16.9±3.6)months.In the PFNA and PFLCP groups,the operation time was respectively(57.6±6.8)min and(77.4±6.5)min,the intraoperative blood loss was(128.3±50.3)ml and(156.3±23.9)ml,postoperative bed time was(4.0±2.5)days and(8.1±2.0)days,Harris score at 6 months post-operative was(45.3±8.6)points and(36.3±7.0)points.There were significant differences between two groups(P＜0.05).Inci-dence of postoperative complications was 19.4％(7/36)and 34.5％(10/29),Harris score at 1 year postoperative was(60.8±6.7)points and(59.0±8.1)points.There was no significant difference between the two groups(P＞0.05).Conclusion Compared with PFLCP,PFNA treatment of elderly patients with knee osteoarthritis between the femoral intertrochanteric fractures shorter surgical time,less intraoperative blood loss,bed rest after surgery,short-term hip function recovery better,when the affected knee joint can tolerate traction,can be used as a priority.

This study aims to investigate the effect of Linggui Zhugan Decoction(LGZGD) on autophagy in the mouse model of chronic heart failure(CHF) induced by myocardial infarction(MI), as well as the regulatory effect of LGZGD on the hypoxia-inducible factor-1α(HIF-1α)/heme oxygenase-1(HO-1) signaling pathway, based on bioinformatics and animal experiments. The active ingredients and corresponding targets of LGZGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database, and GEO, GeneCards, and DisGeNET were searched for the disease targets. Cytoscape was used to establish a "drug-component-target" network. The protein-protein interaction(PPI) network analysis was performed on STRING. R language was used for Gene Ontology(GO) and Kyoto Encycloperfia of Genes and Genomes(KEGG) enrichment analyses. Molecular docking was adopted to validate the core targets. The mouse model of MI-induced CHF was established by surgical ligation of the left anterior descending coronary artery. The modeled mice were assigned into the sham, model, low-, medium-, and high-dose(2.34, 4.68, and 9.36 g·kg~(-1), respectively) LGZGD, and captopril(3.25 mg·kg~(-1)) groups. After continuous administration for 6 weeks, a Doppler ultrasound imaging system was used to examine the heart function indicators: left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular end-systolic dimension(LVIDs), and left ventricular end-diastolic dimension(LVIDd). The myocardial tissue was stained with hematoxylin-eosin for the observation of morphological changes. The mRNA levels of microtubule-associated protein 1 light chain 3 beta(LC3B), Beclin1, p62, HIF-1α, and HO-1 in the myocardial tissue were determined by RT-qPCR. The protein levels of LC3B, beclin1, p62, autophagy-related protein 5(ATG5), HIF-1α, and HO-1 were determined by Western blot. The results showed that 103 active components of LGZGD, corresponding to 224 targets, were obtained. A total of 3 485 and 6 165 targets related to MI and CHF, respectively, were retrieved. The GSE16499 dataset obtained 3 263 differentially expressed genes. There were 31 common targets. The top 3 core active components were quercetin, naringenin, and 1-methoxyphaseollidin. The topology analysis results showed that the core targets were MAPK3, HMOX1(HO-1), MYC, ADRB2, PPARD, and HIF1A(HIF-1α). The molecular docking results showed strong binding between the core targets and the main active components of LGZGD. LGZGD significantly improved the heart function and alleviated the pathological changes in the myocardial tissue of mice. Western blot and RT-qPCR results showed that the HIF-1α/HO-1 signaling pathway and autophagy were activated in the model group. LGZGD up-regulated the levels of LC3B, Beclin1, ATG5, HIF-1α, and HO-1 while down-regulating the mRNA and protein levels of p62. In summary, LGZGD can enhance autophagy and improve the heart function in the mouse model of CHF after MI by upregulating the HIF-1α/HO-1 signaling pathway.
Animals ; Drugs, Chinese Herbal/chemistry* ; Myocardial Infarction/drug therapy* ; Heart Failure/physiopathology* ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Signal Transduction/drug effects* ; Male ; Computational Biology ; Heme Oxygenase-1/genetics* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Mice, Inbred C57BL ; Humans ; Chronic Disease ; Disease Models, Animal

OBJECTIVE: To evaluate the clinical features, laboratory and imaging results, treatment and outcomes of eosinophilic fasciitis (EF) and assess the value of ultrasound in the diagnosis of EF. METHODS: We retrospectively analyzed the clinical data of 45 patients with EF treated in our center from January 1, 2006 to February 28, 2022. The consistency between the diagnoses of EF based on ultrasound and MRI findings was assessed. RESULTS: In the 45 EF patients (male/female ratio 3.5:1), the age of onset ranged from 16 to 64 years with a mean disease course of 22.6 months. The average time from symptom onset to diagnosis was 16 months. The most common possible trigger of the disease was vigorous exercise (10/45), causing symmetrical lesions in the limbs, most commonly in the forearms (86.7%) and lower legs (80%). Clinical features of EF included subcutaneous swelling and induration (95.6%), arthralgia and arthritis (55.6%), groove sign (42.2%), hand joint contractures (42.2%), skin pigmentation (37.8%), and peau d'orange appearance (13.3%). Eosinophilia was found in 31 patients (68.9%). Hypergammaglobulinemia was seen in 23/44 (52.3%) and positive antinuclear antibodies in 9 (20%) of the patients. Twentyone of the patients were treated with high-dose methylprednisolone (≥200 mg daily for 3 to 5 consecutive days), and compared with the patients who did not receive this treatment, these patients more frequently experienced relapse before admission, had more extensive involvement, and had a higher rate of hypergammaglobulinemia without fever, but these differences were not statistically significant. Of the 31 patients (68.9%) with follow-up data (for a median of 3.2 years [range 0.2-15.9]), complete remission was achieved in 12 (38.7%) patients, and the accumulative complete remission rate was 44.1% at 5.5 years. No specific baseline characteristics or immunosuppressants were found to correlate with the treatment response. A total of 26 patients underwent both ultrasound and MRI examination, and the Kappa value of the diagnostic results between ultrasound and MRI was 0.91. CONCLUSION EF is characterized by symmetrical subcutaneous swelling and induration in the limbs, accompanied by eosinophilia and hypergammaglobulinemia. Glucocorticoid is effective for treating EF. Ultrasound examination can identify thickening of subcutaneous fascia for an early diagnosis of EF.
Humans ; Female ; Male ; Infant ; Child, Preschool ; Retrospective Studies ; Hypergammaglobulinemia ; Eosinophilia ; Ultrasonography ; Hand ; Contracture ; Treatment Outcome

OBJECTIVE: The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment. METHODS: Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ. RESULTS: Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein β1 (Hspb1) was the highest in the EA group compared to the model group. CONCLUSION EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Proteomics ; Cognitive Dysfunction/therapy* ; Hippocampus

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.
Aged ; Male ; Humans ; Aged, 80 and over ; Female ; Heart Failure/pathology* ; Retrospective Studies ; Stroke Volume ; Case-Control Studies ; Nucleic Acids ; 8-Hydroxy-2'-Deoxyguanosine ; Myocytes, Cardiac/pathology* ; RNA ; Oxidative Stress ; Guanine ; Ventricular Function, Left

Objective: To evaluate the safety of simultaneous administration of quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and older. Methods: From November 2021 to May 2022, eligible participants aged 60 years and older were recruited in Taizhou City, Jiangsu Province, China, and a total of 2 461 participants were ultimately enrolled in this study. Each participant simultaneously received one dose of quadrivalent influenza split virion vaccine and one dose of 23-valent pneumococcal polysaccharide vaccine. The safety was observed within 28 days after vaccination. Safety information was collected through voluntary reporting and regular follow-ups. Results: All 2 461 participants completed the simultaneous administration of both vaccines and the safety follow-ups for 28 days after vaccination. The mean age of the participants was (70.66±6.18) years, with 54.61% (1 344) being male, and all participants were Han Chinese residents. About 22.51% (554) of the participants had underlying medical conditions. The overall incidence of adverse reactions within 0-28 days after simultaneous vaccination was 2.07% (51/2 461), mainly consisting of Grade 1 adverse reactions [1.83% (45/2 461)], with no reports of Grade 4 or higher adverse reactions or vaccine-related serious adverse events. The incidence of local adverse reactions was 0.98% (24/2 461), primarily presenting as pain at the injection site [0.93% (23/2 461)]. The incidence of systemic adverse reactions was 1.42% (35/2 461), with fever [0.85% (21/2 461)] being the main symptom. In the group with underlying medical conditions and the healthy group, their overall incidence of adverse reactions was 2.53% (14/554) and 1.94% (37/1 907), respectively. The incidence of local adverse reactions in the two groups was 1.62% (9/554) and 0.79% (15/1 907), respectively, and the incidence of systemic adverse reactions was 1.44% (8/554) and 1.42% (27/1 907), respectively, with no statistically significant differences between them (all P>0.05). Conclusion: It is safe for adults aged 60 years and older to receive quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine at the same time.