Objective To investigate the expression of miR-31a-5p in myocardial infarction (MI) mice and its potential mechanism. Methods A dataset was downloaded from the gene expression database, and miR-31a-5p and its predicted target gene hypoxia-inducible factor-1α (HIF-1α) were screened using bioinformatics methods. The MI model was established by ligating the left anterior descending branch of the coronary artery in C57BL/6J male mice which were randomly divided into sham and MI groups (n=6 in each group). The in vitro hypoxic cell model was induced by treatment of H9c2 cells with cobalt chloride (CoCl2) and divided into a control group, a model group, a NC group, a miR-31a-5p mimic group and a miR-31a-5p inhibitor group. The degree of myocardial tissue fibrosis was stained by Masson and analyzed. The expression levels of miR-31a-5p and HIF-1α mRNA in mouse myocardial tissues and H9c2 cells were detected by qRT-PCR. Western blotting was used to detect the expression levels of B-cell lymphoma 2 (Bcl-2), cleaved-caspase 3 apoptotic protein in mouse myocardial tissues and HIF-1α and apoptotic protein in H9c2 cells, respectively. The dual luciferase reporter gene assay was used to verify the targeting relationship between miR-31a-5p and HIF-1α. Results Masson staining showed significantly increased fibrosis in MI mice (P<0.000 1); miR-31a-5p, cleaved-caspase 3 were significantly elevated and Bcl-2 was decreased in MI mice and CoCl2 treated H9c2 (P<0.05). The results of dual luciferase reporter assay showed that the relative luciferase activity of miR-31a-5p mimic cotransfected with HIF-1α-3'-UTR WT plasmid was reduced (P<0.000 1); miR-31a-5p mimic decreased HIF-1α expression and increased apoptotic protein levels in CoCl2 induced H9c2 cells (both P<0.05), while miR-31a-5p exerted the opposite effect. Conclusion miR-31a-5p can aggravate apoptosis in myocardial ischemia by targeting HIF-1α.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.
Humans ; Autophagy ; Diabetes Mellitus ; Diabetic Neuropathies/complications* ; Medicine, Chinese Traditional ; Oxidative Stress ; Schwann Cells/pathology*

In 2020, the prevalence of abnormal spinal curvature among 54 079 students in Shandong Province was 1.54%. The multivariate logistic regression model analysis showed that, compared with those in primary school, economically underdeveloped areas, and non-residential schools, students in middle and high schools, economically average areas, and residential schools had a higher risk of abnormal spinal curvature, with OR (95%CI) values of 2.029 (1.662-2.476), 2.746 (2.208-3.416), 2.237 (1.740-2.875) and 2.057 (1.705-2.483), respectively. Compared with those in economically underdeveloped areas, who were underweight, who had seat adjustments≤1 time per academic year, and who had physical education classes≤1 per week, students in economically developed areas, who were normal weight, overweight, and obese, who had seat adjustments≥2 times per academic year, and who had physical education classes 2-3 or≥4 per week, had a lower risk of abnormal spinal curvature, with OR (95%CI) values of 0.690 (0.521-0.915), 0.722 (0.546-0.955), 0.535 (0.389-0.735), 0.383 (0.274-0.535), 0.835 (0.711-0.980), 0.561 (0.474-0.663) and 0.491 (0.315-0.766), respectively.
Humans ; Risk Factors ; Prevalence ; Spinal Curvatures ; Schools ; Students

In 2020, the prevalence of abnormal spinal curvature among 54 079 students in Shandong Province was 1.54%. The multivariate logistic regression model analysis showed that, compared with those in primary school, economically underdeveloped areas, and non-residential schools, students in middle and high schools, economically average areas, and residential schools had a higher risk of abnormal spinal curvature, with OR (95%CI) values of 2.029 (1.662-2.476), 2.746 (2.208-3.416), 2.237 (1.740-2.875) and 2.057 (1.705-2.483), respectively. Compared with those in economically underdeveloped areas, who were underweight, who had seat adjustments≤1 time per academic year, and who had physical education classes≤1 per week, students in economically developed areas, who were normal weight, overweight, and obese, who had seat adjustments≥2 times per academic year, and who had physical education classes 2-3 or≥4 per week, had a lower risk of abnormal spinal curvature, with OR (95%CI) values of 0.690 (0.521-0.915), 0.722 (0.546-0.955), 0.535 (0.389-0.735), 0.383 (0.274-0.535), 0.835 (0.711-0.980), 0.561 (0.474-0.663) and 0.491 (0.315-0.766), respectively.
Humans ; Risk Factors ; Prevalence ; Spinal Curvatures ; Schools ; Students

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective:To observe the possible toxicity of long-term intravenous injection of Tanreqing injection in Beagle dogs， so as to provide experimental data for its clinical safe medication. Method:A total of 32 Beagle dogs （16 males and 16 females） were randomly divided into the low- （2.5 mL·kg^-1）， medium- （5.0 mL·kg^-1）， and high-dose （10.0 mL·kg^-1） Tanreqing injection groups and control group according to their body mass indices， with eight dogs in each group. In the waking state， the dogs were treated with intravenous injection of corresponding drugs into the medial cephalic vein of forelimb for 13 weeks， followed by four-week drug withdrawal. After the observation of general condition， body mass， and food consumption， the Beagle dogs were subjected to electrocardiography， ophthalmoscopy， hematological examination， serum biochemistry， and blood coagulation test in the middle of medication （week 6）， at the end of medication （week 13）， and during recovery （week 17）. Then the gross anatomy was conducted for calculating the major organ coefficients and observing the histopathological changes. Result:No obvious toxic reaction was found in each group， but the decreased fibrinogen and increased Kupffer's cells phagocytizing yellow-brown pigment in hepatic sinusoids were observed in the high-dose Tanreqing injection group following three months of medication. Reduction of fibrinogen was not observed in recovery period， but Kupffer's cells that phagocytized yellow-brown pigment still existed. Conclusion:The intravenous injection of Tanreqing injection at 2.50 mL·kg^-1 （low dose）， 5.00 mL·kg^-1 （medium dose） or 10.00 mL·kg^-1 （high dose） for three months in Beagle dogs resulted in no obvious toxic reaction. However， it is still suggested to test the liver function and blood coagulation after long-term administration of high-dose Tanreqing injection.

italic>Astragalus polysaccharides are the main immunomodulatory substances in Astragali Radix. The structure of polysaccharides is difficult to accurately determine, which limits the in-depth study of the molecular mechanism of Astragalus polysaccharides in vivo. "Polysaccharide receptor theory" believes that there are one or more oligosaccharide fragment "active centers" in immunologically active polysaccharide molecules. Therefore, the degradation of Astragalus polysaccharides into oligosaccharides and the study of the active centers of polysaccharides at the oligosaccharide level provide new ideas in the study of the structure and mechanism of Astragalus polysaccharides. This article adopts endo-α-1,4-glucanase enzymatic hydrolysis, and determines the best degradation conditions through single factor test and orthogonal test to degrade the immunologically active polysaccharide APS-Ⅱ (10 kDa component) into oligomers with different degrees of polymerization. Then through the preparation of polyacrylamide gel chromatography and specific immune and non-specific immune cell tests, the immune activity screening of different oligosaccharide components is carried out. The animal welfare and the experimental process in this study follow the requirements of the Animal Ethics Committee of Shanxi University. The results showed that compared with the immunologically active polysaccharide APS-Ⅱ, different oligosaccharide components have obvious differences in different immunological activities. This paper studies the different immunological activities of Astragalus polysaccharides at the level of oligosaccharides, laying a foundation for further elucidating the structure and function of Astragalus polysaccharides, enriching the theory of polysaccharide receptors, and providing new ideas for the development of Astragalus polysaccharides.

We previously reported that active Astragalus polysaccharides APS-Ⅱ generate strong immune activity. Here we establish the optimal method for APS-II acid degradation. After preliminary structural studies and separation and preparation of the degradation products, the oligosaccharide active center with the strongest immune activity was identified by in vitro immune cell culture experiments. The optimum acid degradation conditions for APS-II were determined by a single factor experiment and an orthogonal experiment. Astragalus oligosaccharides prepared under the optimal conditions were subjected to structural analysis by hydrophilic interaction chromatography - electrospray ionization source - high resolution time-of-flight mass spectrometry. The products were separated and oligosaccharide fragments with different degrees of polymerization were isolated by preparative purification chromatography. Finally, fragments of the immunologically active centers were identified by in vitro immune cell cultures from multiple perspectives. The results show that the optimal acid hydrolysis conditions for APS-Ⅱ are hydrolysis temperature 80 ℃, trifluoroacetic acid concentration 1.0 mol·L^-1, hydrolysis time 1 h. The degradation conditions have good repeatability. The degradation product is a six-carbon aldehyde glycan structure with the main chain 1→4 connected. The immune activity screening experiment for six oligosaccharide fragments showed that larger molecular weight oligosaccharides have stronger immune-promoting effects. It is speculated that the immunologically active center of Astragalus oligosaccharide is located in the sugar chain of DP9-DP19. The animal welfare and the experimental process in this study follow the requirements of the Animal Ethics Committee of Shanxi University. This result suggests a foundation for the structural characterization and structure-activity relationship research of Astragalus oligosaccharides, and may promote the development of Astragalus oligosaccharide drugs.