This study explores the effect of total secondary ginsenosides(TSG) on apoptosis and energy metabolism in H9c2 cells under hypoxia and its potential mechanisms. H9c2 cell viability was observed and the apoptosis rate was calculated to determine suitable intervention concentrations of TSG, antimycin A complex(AMA), and coenzyme Q10(CoQ10), along with the duration of hypoxia. H9c2 cells at the logarithmic phase were divided into a normal group, a model group, a TSG group, an AMA group, a TSG+AMA group, and a CoQ10 group. All groups, except the normal group, were treated with their respective intervention drugs and cultured under hypoxic conditions. Adenosine triphosphate(ATP) content and creatine kinase(CK) activity were measured using an ATP chemiluminescence assay kit and a CK colorimetric assay kit. Flow cytometry was used to assess apoptosis rates, and Western blot evaluated the expression levels of apoptosis-related proteins, including B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cysteinyl aspartate-specific protease(caspase)-3, caspase-8, and caspase-9, as well as mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α), estrogen-related receptor-α(ERRα), nuclear respiratory factor(NRF)-1, NRF-2, peroxisome proliferator activated receptor-α(PPARα), and Na~+-K~+-ATPase. RT-PCR was employed to analyze the mRNA expression of mitochondrial biogenesis factors, including PGC-1α, ERRα, NRF-1, NRF-2, PPARα, mitochondrial transcription factor A(TFAM), mitochondrial cytochrome C oxidase 1(COX1), and mitochondrial NADH dehydrogenase subunit 1(ND1), ND2. The selected intervention concentrations were 7.5 μg·mL~(-1) for TSG, 10 μmol·L~(-1) for AMA, and 1×10~(-4) mol·L~(-1) for CoQ10, with a hypoxia duration of 6 h. Compared with the normal group, the model group showed decreased ATP content and CK activity, increased apoptosis rates, decreased Bcl-2 expression, and increased Bax, caspase-3, caspase-8, and caspase-9 expression in H9c2 cells. Additionally, the protein and mRNA expression levels of mitochondrial biogenesis-related factors(PGC-1α, ERRα, NRF-1, NRF-2, PPARα), mRNA expression of TFAM, COX1, and ND1, ND2, and protein expression of Na~+-K~+-ATPase in mitochondrial DNA, were also reduced. In the TSG and CoQ10 groups, ATP content and CK activity increased, and apoptosis rates decreased compared with those in the model group. The TSG group showed decreased protein expression of apoptosis-related proteins Bax, caspase-3, caspase-8, and caspase-9, increased protein and mRNA expression of mitochondrial biogenesis factors PGC-1α, ERRα, NRF-1, and PPARα, and increased NRF-2 protein expression and TFAM mRNA expression in mitochondrial DNA. Conversely, in the AMA group, ATP content and CK activity decreased, the apoptosis rate increased, Bcl-2 expression decreased, and Bax, caspase-3, caspase-8, and caspase-9 expression increased, alongside reductions in PGC-1α, ERRα, NRF-1, NRF-2, PPARα protein and mRNA expression, as well as TFAM, COX1, ND1, ND2 mRNA expression and Na~+-K~+-ATPase protein expression. Compared with the TSG group, the TSG+AMA group exhibited decreased ATP content and CK activity, increased apoptosis rates, decreased Bcl-2 expression, and increased Bax, caspase-3, caspase-8, and caspase-9 expression, along with decreased PGC-1α, ERRα, NRF-1, NRF-2, and PPARα protein and mRNA expression and TFAM, COX1, and ND1, ND2 mRNA expression. Compared with the AMA group, the TSG+AMA group showed increased CK activity, decreased apoptosis rate, increased Bcl-2 expression, and decreased Bax, caspase-8, and caspase-9 expression. Additionally, the protein and mRNA expression of PGC-1α, ERRα, NRF-1, PPARα, mRNA expression of TFAM, COX1, ND1, ND2, and Na~+-K~+-ATPase protein expression increased. In conclusion, TSG enhance ATP content and CK activity and inhibit apoptosis in H9c2 cells under hypoxia, and the mechanisms may be related to the regulation of PGC-1α, ERRα, NRF-1, NRF-2, PPARα, and TFAM expression, thus promoting mitochondrial biogenesis.
Apoptosis/drug effects* ; Ginsenosides/pharmacology* ; Energy Metabolism/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Line ; Cell Hypoxia/drug effects* ; Organelle Biogenesis ; Adenosine Triphosphate/metabolism* ; Humans ; Cell Survival/drug effects*

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

AIM: To observe the efficacy of moderate and high myopia patients with vault greater than 1 000μm after implantation of phakic posterior chamber implantable contact lens(ICL).METHODS: A total of 42 patients(73 eyes)who received ICL implantation in the hospital and had postoperative vault greater than 1 000 μm between January 2014 and January 2017 were selected and retrospectively studied. Changes in visual acuity, intraocular pressure, corneal endothelial cell density, anterior chamber-related parameters(chamber angle, central anterior chamber depth, anterior chamber volume)and vault were compared among patients before surgery, at 1, 3, 6mo and 1a after surgery and at the last follow-up.RESULTS: The uncorrected visual acuity(UCVA)at 1, 3, 6mo and 1a after surgery and at the last follow-up was better than that before surgery(all P<0.05), and the chamber angle, central anterior chamber depth and anterior chamber volume were smaller or lower than those before surgery(all P<0.05), but there were no statistical differences in UCVA, chamber angle, central anterior chamber depth and anterior chamber volume at each time point after surgery(all P>0.05). The intraocular pressure at 1mo after surgery was lower than that before surgery(P<0.05), but the intraocular pressure at 3, 6mo and 1a after surgery and at the last follow-up was not statistically different from that before surgery(all P>0.05). There was no statistical significance in the corneal endothelial cell density at 1, 3, 6mo and 1a after surgery and at the last follow-up compared with that before surgery(all P>0.05). The vault at 1, 3, 6mo and 1a after surgery and at the last follow-up showed a decreasing trend, and the difference was statistically significant at each time point after surgery(all P<0.05).CONCLUSION: The short-term and long-term efficacy are better in moderate and high myopia patients with vault greater than 1 000 μm after ICL implantation, and there are no significant effects on the intraocular pressure and corneal endothelial cell. The postoperative anterior chamber structure is relatively stable and the vault tends to decrease over time. In most cases, close observation is sufficient and intraocular lens replacement is generally not required.

Abstract: Objective To analyze and compare the effects of different clinical characteristics on the negative conversion time of nucleic acid detection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a scientific basis for the isolation and treatment of coronavirus disease 2019 (COVID-19). Methods　The epidemiological and clinical data of 228 mild SARS-CoV-2 Omicron variant infected patients diagnosed in Shanghai were retrospectively collected from April 27, 2022 to June 8, 2022 in Wujiaochang designated Hospital, Yangpu District, Shanghai. The negative conversion time of nucleic acid detection was used as the outcome variable, and the patients were divided into A (≤18 days) and B (>18 days). Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of the negative conversion time of nucleic acid detection. Results　The mean nucleic acid conversion time of 228 patients was (18.7±12.1) d, with the median time of 18 (2-46) d. Among them, 120 patients in group A had an average nucleic acid conversion time of (13.2±2.0) d, and 108 cases in group B had an average nucleic acid conversion time of (20.8±1.3) d. Univariate analysis showed that there were no statistically significant differences in the effects of hypertension, coronary heart disease, diabetes, hypokalemia, malignant tumors, neuropsychiatric diseases, chronic digestive diseases on the negative nucleic acid conversion time (P>0.05); however, there were significant differences in the effects of combined cerebrovascular disease, leukopenia, chronic respiratory system diseases and vaccination on the negative nucleic acid conversion time (P<0.05). Further multivariate logistic regression analysis revealed that the combination of chronic respiratory diseases and non-vaccination were significant risk factors for prolongation of negative nucleic acid conversion time (P<0.05). Conclusions The results of this study show that gender, age and whether hypertension, coronary heart disease, diabetes mellitus, hypokalemia, malignant tumor, neuropsychiatric disease and chronic digestive disease have no significant effect on the nucleic acid conversion time, whereas chronic respiratory disease and no vaccination are significantly correlated with the prolongation of nucleic acid conversion time in SARS-CoV-2 Omicron-infected patients.

Objective: To understand the detection rate, epidemic pattern of respiratory syncytial virus (RSV) in hospitalized children with acute lower respiratory tract infection (ALRTI) in China. Methods: From June 2017 to March 2020, a prospective multi-center study on the viral aetiology among hospitalized children with ALRTI was conducted in six pediatrics hospital of North China, Northeast, Northwest, South China, Southeast, and Southwest China. A total of 2 839 hospitalized children with ALRTI were enrolled, and the respiratory specimens were collected from these cases. A multiplex real-time RT-PCR assay were employed to screen the respiratory viruses, and the molecular epidemiological and clinical characteristics of children infected with RSV were analyzed. Results: The positve rate of RSV was 18.6% (528/2 839), and the positive rate of RSV in different regions ranged from 5.5% to 44.3%. The positive rate of RSV in male was higher than that in female (20.2% vs 16.3%), and there was a significant statistically difference between two groups (χ2=6.74, P=0.009). The positive rate of RSV among children under 5 years old was higher than that among children older than 5 years old (22.3% vs 4.5%), and there was a significant statistically difference between two groups (χ2=97.98,P<0.001). The positive rate of RSV among the <6 months age group was higher than that of other age groups (all P<0.05). During January 2018 and December 2019, RSV was detected in almost all through the year, and showed peaks in winter and spring. RSV-positive cases accounted for 17.0% (46/270) among children with severe pneumonia, including 36 cases infected with RSV alone. Conclusion: RSV is an important viral pathogen in children under 5 years old with ALRTI in China. The virus can be detected almost all through the year and reached the peak in winter and spring. RSV could lead to severe pneumonia in children and caused huge threaten to children's health.
Child ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Respiratory Syncytial Virus Infections/epidemiology* ; Child, Hospitalized ; Prospective Studies ; Respiratory Tract Infections/epidemiology* ; Respiratory Syncytial Virus, Human ; China/epidemiology*

Objective:To analyze the dominant genotypes and epidemic characteristics of human rhinovirus (HRV) in pediatric community-acquired pneumonia (CAP) in China.Methods:Between June 2017 to December 2019, throat swabs or nasopharyngeal aspirates were collected from pediatric CAP patients hospitalized in 6 medical institutions in Southern and Northern China (bounded by Qinling and Huaihe River), respectively.A total of 16 species of common respiratory viruses were screened using respiratory pathogen detection kits.Samples with positive HRV were genotyped for further epidemiological analysis.Results:The total detection rate of HRV in pediatric CAP (2 913 cases) was 12.2%(356 cases) in this study, which was 10.3%(145/1 410 cases) and 14.0%(211/1 503 cases) in Northern and Southern China, respectively.The detection rate of HRV in the Southern region was significantly higher than that in the Northern region, the difference was statistically significant( χ2=9.562, P=0.002). Epidemiological analysis showed that the distribution of HRV-positive cases in the Northern region was similar in all age groups, while 90.5% of positive cases in the Southern region were infants under 3 years.Classified by seasonal distribution, HRV-positive cases in the Northern region were mainly distributed in summer and autumn, while those in the Southern region were mainly distributed in spring and autumn.The coinfection rate of HRV and other pathogens was 40.7%, which was significantly higher in the Southern region than that of Northern region (49.0% vs.28.0%), the difference was statistically significant( χ2=15.801, P<0.001). The most common pathogens mixed with HRV were respiratory syncytial virus (RSV), human boca virus (HBOV) and parainfluenza virus type Ⅲ (PIV3) in the Northern region, with the mixed infection rate of 5.0%, 5.0% and 4.0%, respectively, which were RSV, PIV3 and human metapneumovirus (HMPV) in the Southern region, with the mixed infection rate of 9.0%, 7.0% and 6.0%, respectively.The genotyping results showed that all three HRV genotypes were detected.HRV-A (118/220 cases) was the dominant genotype, followed by HRV-C(82/220 cases). Conclusions:The detection rate of HRV in pediatric CAP cases is 12.2% in this study.There are significant differences in age and seasonal distribution of HRV-positive cases in the Southern and Northern regions.Coinfection of HRV and other pathogens is detected.The coinfection rate is significantly higher in the Southern region than that in the Northern region.HRV-A is the dominant genotype, followed by HRV-C.

The important function of the endplate is to transmit stress and supply nutrition. Endplate degeneration might induce or promote degeneration of the intervertebral disc, causing a series of spine diseases that seriously impair people’s health and life quality. Endplate chondrocytes can respond to mechanical stimulation, which is an important factor affecting endplate degeneration. Inappropriate mechanical stimulation will accelerate endplate degeneration. This review summarized the effects of mechanical stimulation on vertebral endplate chondrocyte apoptosis, synthesis inhibition, calcification, and extracellular matrix degradation. The endplate degeneration induced by mechanical stimulation is regulated by a complex network of signal pathways composed of various signal transduction factors. The signal pathways involved in this review included NF-κB, Wnt, Hedgehog, MAPK, RhoA/Rock-1, AKT/mTOR, TGF-β signaling pathway and miRNA related signals. The interconnection of these pathways was highlighted and summarized. Multiple signaling pathways work together to regulate endplate chondrocyte metabolism, which ultimately leads to the endplate degeneration. This review might shed light on early diagnosis and precise treatment of cartilage endplate degeneration.

OBJECTIVE: To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design. METHODS: Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators. RESULTS: Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed. CONCLUSION Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.
Administration, Cutaneous ; Adult ; Aged ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Intestinal Neoplasms ; complications ; secondary ; Intestinal Obstruction ; drug therapy ; etiology ; Male ; Middle Aged ; Ultrasonic Therapy ; methods

Traditional Chinese Medicine (TCM) is one of the oldest systems of medicine. More and more attention has been paid to TCM application, but the variable quality of clinical trials with TCM impedes its widespread acceptance. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement has established guidelines for designing clinical trials to ensure that the trial results are accurate and reliable. However, there are difficulties when applying SPIRIT 2013 Statement to trials with TCM, due to the unique theory and the characteristic of TCM intervention. An Extension to the original SPIRIT was developed to ensure the quality of trial design with TCM. As Chinese herbal formulae, acupuncture and moxibustion are common and representative interventions in TCM practice, the executive working group determined that the SPIRIT-TCM Extension focus on these three interventions. Extension was developed through initiation, 3 rounds of Delphi consensus survey, and finalizing expert meeting. Seven items from the SPIRIT 2013 Statement were modified, namely, "title", "background and rationale", "objectives", "eligibility criteria", "interventions", "outcomes", and "data collection methods". The Extension includes the introduction of the concept of TCM pattern and 3 major TCM interventions, with examples and explanations. The SPIRIT-TCM Extension 2018 provides suggestion for investigators in designing high quality TCM clinical trials. It is expected that wide dissemination and application of this extension ensure continuous improvement of TCM trial quality throughout the world.
Clinical Protocols ; Clinical Trials as Topic ; Humans ; Medicine, Chinese Traditional ; Research Design

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].
Constipation ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Outcome Assessment (Health Care) ; Prospective Studies ; Randomized Controlled Trials as Topic