Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures / 药学学报

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review / 中华儿科杂志

Objective: To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation. Methods: This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized. Results: The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations. Conclusions: Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.

Effect of Gualou Xiebai Decoction on pulmonary fibrosis in rats based on pyroptosis pathway / 中国中药杂志

This study investigated the effect of Gualou Xiebai Decoction on rats with bleomycin-induced pulmonary fibrosis. The rats were randomly divided into a control group, a model group, a low-dose Gualou Xiebai Decoction group(2.4 g·kg~(-1)), a high-dose Gualou Xiebai Decoction group(4.8 g·kg~(-1)), and pirfenidone group(150 mg·kg~(-1)). The model of pulmonary fibrosis was established by intratracheal instillation of bleomycin in all groups, except the control group. Since the second day of modeling, the corresponding drugs were given to rats by intragastric administration, once a day for 14 d and 28 d. The hematoxylin-eosin(HE) staining was used to evaluate the degree of inflammatory injury in lung tissues. The immunofluorescence staining was used to detect the expression of CD68 and CD163 in lung tissues of rats. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in serum and brochoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay(ELISA). The expression of pyroptosis-related genes in lung tissues of rats was detected by qRT-PCR. The results of HE staining and immunofluorescence staining showed that the lung tissue structure was normal in the control group. In addition, there were alveolar collapse or even closure in lung tissues of rats in the model group, with obvious inflammatory cell infiltration, and the expression of CD68 and CD163 was significantly up-regulated. As compared with the model group, the lung tissue structure of rats in the Gualou Xiebai Decoction groups was significantly improved, with alleviated inflammation, and the expression of CD68 and CD163 was decreased. As compared with the control group, the level of TNF-α in serum and BALF of rats in the model group was significantly increased(P<0.01), the mRNA expression levels of alpha smooth muscle actin(α-SMA), collagen type Ⅰ alpha 1 chain(Col1a1), caspase-1, IL-1β, IL-18, gasdermin D(Gsdmd), and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in lung tissues were significantly increased(P<0.05, P<0.01), and the mRNA expression level of E-cadherin was significantly decreased(P<0.01). As compared with the model group, the level of TNF-α in serum and BALF was significantly down-regulated in the high-dose Gualou Xiebai Decoction group(P<0.05, P<0.01), and that of IL-10 was up-regulated(P<0.05, P<0.01). The mRNA expression levels of α-SMA, Col1a1, caspase-1, IL-18, Gsdmd, NLRP3 and IL-1β in lung tissues were significantly decreased(P<0.05, P<0.01) in the high-dose Gualou Xiebai Decoction group, and the mRNA expression level of E-cadherin was significantly increased(P<0.05, P<0.01). In conclusion, Gualou Xiebai Decoction can down-regulate the levels of inflammatory factors and related genes and effectively mitigate pulmonary fibrosis by regulating the pyroptosis pathways.

Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics / 中国中药杂志

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.

Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase Ⅱb clinical trial / 中国中药杂志

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction / 中国中药杂志

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Clinical Effect of Surgical Reconstruction of Extracranial Vertebral Artery / 中国医学科学院学报

Objective To evaluate the effect of surgical reconstruction of extracranial vertebral artery and to summarize the experience. Methods The clinical data of 15 patients undergoing surgical reconstruction of extracranial vertebral artery from September 2018 to June 2022 were collected.The operation methods,operation duration,intraoperative blood loss,operation complications,and relief of symptoms were retrospectively analyzed. Results Eleven patients underwent vertebral artery (V1 segment) to common carotid artery transposition,two patients underwent endarterectomy of V1 segment,two patients underwent V3 segment to external carotid artery bypass or transposition.The operation duration,intraoperative blood loss,and blocking time of common carotid artery varied within 120-340 min,50-300 ml,and 12-25 min,with the medians of 240 min,100 ml,and 16 min,respectively.There was no cardiac accident,cerebral hyperperfusion syndrome,cerebral hemorrhage or lymphatic leakage during the perioperative period.One patient suffered from cerebral infarction and three patients suffered from incomplete Horner's syndrome after the operation.During the follow-up (4-45 months,median of 26 months),there was no anastomotic stenosis,new cerebral infarction or cerebral ischemia. Conclusion Surgical reconstruction of extracranial vertebral artery is safe and effective,and individualized reconstruction strategy should be adopted according to different conditions.

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Effects of propofol on glutamatergic neuronal activity in paraventricular thalamus / 药学学报

This study explored the effects of propofol on the activity of glutamatergic neurons in the paraventricular thalamus (PVT) and the underlying mechanisms at the molecular level using whole-cell patch-clamp techniques. Acute brain slices containing the PVT were obtained from 8 weeks old C57BL/6J mice. The electrophysiological characteristics of PVT neurons were recorded in current-clamp mode, then single-cell sequencing was used to identify neuronal types. The firing frequencies before, during, and after propofol or intralipid application were recorded as FB, FD and FW; and the membrane potentials were recorded as MPB and MPD. Picrotoxin (PTX) was used to block inhibitory gamma-aminobutyric acid type A (GABAA) receptors during the application of propofol at 10 μmol·L-1. Then, GABAA receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) were recorded, and the effects of 10 μmol·L-1 propofol were investigated. The animal experiments were approved by the Medical Animal Administrative Committee of Shanghai Medical College Fudan University. The results showed that there were no significant differences in FB, FD and FW during intralipid and 2 μmol·L-1 propofol application. With propofol at 5, 10 and 20 μmol·L-1, FD decreased significantly when compared with FB, and FW increased significantly as compared with FD (P < 0.01). The inhibition degree of the three concentration groups was significantly different (P < 0.01). In addition, with propofol at 20 μmol·L-1, MPD hyperpolarized significantly (P < 0.01). In the presence of PTX, 10 μmol·L-1 propofol could not suppress the firing frequency of PVT glutamatergic neurons. Propofol at 10 μmol·L-1 prolonged the decay time of sIPSCs (P < 0.01) and mIPSCs (P < 0.05), and increased the amplitude (P < 0.01) of mIPSCs of PVT glutamatergic neurons. Together, these results indicate that propofol can inhibit the activity of PVT glutamatergic neurons in a concentration-dependent and reversible manner, and the effect is likely to be mediated by postsynaptic GABAA receptors.

Baicalin inhibits PDK1 to mediate glucose metabolism reprogramming and intervene rheumatoid arthritis synovial inflammation / 药学学报

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

Efficacy of implantable collamer lens V4c implantation in the treatment of high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the effect of implantable collamer lens V4c(ICL V4c)implantation on high myopia, and the changes in anterior segment morphology.METHODS:A prospective study was conducted on 100 patients(200 eyes)with high myopia who were treated with ICL V4c implantation in the hospital from February 2018 to March 2021. The best corrected visual acuity(BCVA), uncorrected visual acuity(UCVA), intraocular pressure, higher-order aberration, anterior segment morphology [iridocorneal angle(ICA), central anterior chamber depth(ACD), anterior chamber volume(ACV), central corneal thickness(CCT)and K-value(K)], photopic and scotopic contrast sensitivity before operation and 6 and 12mo after operation were comparatively analyzed.RESULTS:All patients were followed-up. UCVA and BCVA were significantly improved at 6 and 12mo after operation(P&#x003C;0.05). Total higher-order aberration, horizontal coma and vertical coma showed no significant difference before and after operation(P&#x003E;0.05). Spherical aberration, ICA, ACD and ACV at 6 and 12mo after operation were significantly smaller than those before operation(P&#x003C;0.05). Under photopic state, the contrast sensitivity of 3.0 and 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P&#x003C;0.05). Under scotopic state, the contrast sensitivity of 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P&#x003C;0.05); there was no significant difference in CCT, K, or intraocular pressure before and after operation(P&#x003E;0.05).CONCLUSION:Although ICA, ACD and ACV in patients with high myopia are reduced after ICL V4c implantation, the operation can effectively improve visual acuity and visual quality.

Mediation of mitochondrial translocator protein by tanshinone ⅡA in apoptosis of HepG2 cells / 中国药理学通报

Aim To investigate the role of mitochondrial translocator protein(TSPO)in the apoptosis of HepG2 cells induced by tanshinone IIA(Tan II A)and the involved mechanism. Methods Following the HepG2 cells treated with Tan ⅡA at 2.5, 5 and 10 μmol·L-1, the cell viability was determined by MTT assay, and intracellular ATP content was determined by luciferin-luciferase method. Oxygen utilization was measured polarographically with a Clark oxygen electrode. Cell apoptosis was determined by Hoechst 33342 staining and flow cytometry. The mitochondrial membrane potential was assessed with JC-1 staining. The intracellular distribution of TSPO was examined by TSPO immunostaining, and the expressions of TSPO, Cyto C, caspase-3, caspase-9 were determined by immunoblotting analysis. Results Tan II A inhibited the proliferation of HepG2 cells in a dose-and time-dependent manner. The treatment with Tan II A inhibited ATP production and oxygen utilization of mitochondria. In addition, Tan ⅡA enhanced TSPO expression and accumulation in nuclei and up-regulated the expression of Cyto C, caspase-3 and caspase-9. Conclusions Tan II A induces the apoptosis of HepG2 cells, which may be related to the TSPO-mediated mitochondrial dysfunction.

Paeonol ameliorates hepatic inflammation and oxidative stress injury on murine with alcoholic liver injury by regulating JAK2/STAT3 signaling pathway / 中国药理学通报

Aim To investigate the mechanism of action of paeonol based on JAK2/STAT3 signaling pathway to ameliorate liver inflammation and oxidative stress injury induced by acute alcohol stimulation in mice. Methods C57BL/6 mice were randomly divided into normal group, model group, silibinin group (36. 8 mg • kg

Gender differences in antidepressant effect of raw Rehmanniae Radix / 中国中药杂志

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

A multi-center analysis of thyroid-stimulating hormone level in apparently healthy elderly population in China / 南方医科大学学报

OBJECTIVE@#To investigate serum thyroid stimulating hormone (TSH) level and its changes with age in apparently healthy Chinese elderly population and analyze the differences between TSH levels detected using Roche and Snibe electrochemiluminescence immunoassay analyzers.@*METHODS@#General clinical data and frozen fasting serum samples were collected from 5451 apparently healthy Chinese elderly individuals (> 60 years) from 10 centers in different geographic regions in China. Thyroid function indexes including TSH level were detected using Roche and Snibe electrochemiluminescence immunoassay analyzer, and the median (2.5% and 97.5% quantiles) TSH level was calculated. The variations of TSH level among the participants with geographic regions, gender, and age (with an interval of 5 years) were analyzed to determine the influence of these factors on TSH level.@*RESULTS@#The reference ranges of serum TSH level established using Roche and Snibe electrochemiluminescence immunoassay analyzers were 0.42-9.47 mU/L and 0.36-7.98 mU/L, respectively, showing significant differences between the two methods (P < 0.001). The TSH levels measured at two centers in Western China were significantly higher than those at the other centers (P < 0.05). In elderly male population, serum TSH level tended to increase with age, which was not observed in elderly female population. At the age of 60-75 years, women generally had higher serum TSH level than men, but this difference was not observed in the population beyond 75 years.@*CONCLUSION@#In elderly population, serum TSH level can vary with geographic region, gender, and age, but there was no need for establishing specific reference ranges for these factors. The differences between different detection methods should be evaluated when interpreting the detection results of TSH level.

Guidelines for management of pediatric acute hyperextension spinal cord injury / 中华创伤杂志(英文版)

Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.

Application of a light-weighted convolutional neural network for automatic recognition of coal workers' pneumoconiosis in the early stage / 中华劳动卫生职业病杂志

Objective: To construct and verify a light-weighted convolutional neural network (CNN), and explore its application value for screening the early stage (subcategory 0/1 and stage Ⅰ of pneumoconiosis) of coal workers' pneumoconiosis (CWP) from digital chest radiography (DR) . Methods: A total of 1225 DR images of coal workers who were examined at an Occupational Disease Prevention and Control Institute in Anhui Province from October 2018 to March 2021 were retrospectively collected. All DR images were collectively diagnosed by 3 radiologists with diagnostic qualifications and gave diagnostic results. There were 692 DR images with small opacity profusion 0/- or 0/0 and 533 DR images with small opacity profusion 0/1 to stage Ⅲ of pneumoconiosis. The original chest radiographs were preprocessed differently to generate four datasets, namely 16-bit grayscale original image set (Origin16), 8-bit grayscale original image set (Origin 8), 16-bit grayscale histogram equalized image set (HE16) and 8-bit grayscale histogram equalized image set (HE8). The light-weighted CNN, ShuffleNet, was applied to train the generated prediction model on the four datasets separately. The performance of the four models for pneumoconiosis prediction was evaluated on a test set containing 130 DR images using measures such as the receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, and Youden index. The Kappa consistency test was used to compare the agreement between the model predictions and the physician diagnosed pneumoconiosis results. Results: Origin16 model achieved the highest ROC area under the curve (AUC=0.958), accuracy (92.3%), specificity (92.9%), and Youden index (0.8452) for predicting pneumoconiosis, with a sensitivity of 91.7%. And the highest consistency between identification and physician diagnosis was observed for Origin16 model (Kappa value was 0.845, 95%CI: 0.753-0.937, P<0.001). HE16 model had the highest sensitivity (98.3%) . Conclusion: The light-weighted CNN ShuffleNet model can efficiently identify the early stages of CWP, and its application in the early screening of CWP can effectively improve physicians' work efficiency.

Assessment of occupational health risk of noise in a plastic products enterprise / 中国职业医学

@#Objective To assess the occupational health risk of noise in a plastic products enterprise and determine the key risk Methods - points. The workplace of a plastic products enterprise and its 388 noise exposed workers were selected as the ， research subjects using a convenient sampling method. The noise intensity in the workplace of the enterprise was measured and - GBZ/T 229.4-2012 the individual noise exposure level and pure tone hearing test were carried out in the noise exposed workers. Classification of Occupational Hazards at Workplaces--Part 4： Occupational Exposure to Noise（ GBZ/T hereinafter referred to as 229.4-2012） - was used to evaluate the hazardous degree of noise in different posts. The risk of high frequency hearing loss （ ） - （ ） - ， ， HFHL and occupational noise induced deafness ONID in noise exposed workers in different posts at 45.0 50.0 55.0 and WS/T 754-2016 Guideline for Risk Management of Occupational Noise Hazard（ 60.0 years of age were predicted using hereinafter WS/T 754-2016）Results referred to as . The noise in the workplace of this plastic product enterprise was found to exceed the - occupational exposure limits with the rate of 46.6%. The maximum level of normalization of equivalent continuous A weighted - （ ） sound pressure level to a nominal 40 h working week of exposure to noise in workers of six posts was 84.0 93.0 dB A . - ， ， ， According to GBZ/T 229.4 2012 the noise hazards of the posts including extrusion premixing unloading and utility - ， maintenance were mild or moderate except for the film and packaging posts. According to WS/T 754 2016 the risks of HFHL in ， ， the film and packaging operators at age ≥50.0 years old were at acceptable risk and the risks of HFHL in operators of extrusion ， ， premixing unloading and utility maintenance at age ≥45.0 years old were at moderate risk or high risk. The risks of ONID for ， the film packaging and utility maintenance operators at age ≥55.0 years old were at acceptable risk or moderate risk. The risksof ONID for extrusion premixing and unloading operators at age ≥50.0 years old were at high risk. Extrusion operators with （ ） exposure to toluene below the occupational exposure limit had a higher risk of HFHL high risk than unloading operators （ ） Conclusion moderate risk at age 45.0 years with the same noise intensity. The noise exposure intensity is high in the ， workplace of the plastic product enterprise. The workers in posts of extrusion premixing and unloading are at high risk levels of HFHL and ONID.

Observation on the composition and distribution of human papillomavirus infection and its aging changes in female genital tract of Zhuang and Han nationality in Guangxi / 中华老年医学杂志

Objective:To study the composition and distribution of human papillomavirus(HPV)in female genital tract of Zhuang and Han nationality in Guangxi.Methods:The composition and distribution of cervical human papillomavirus(HPV)infection in Han and Zhuang women visiting Department of Gynecology and Obstetrics of the First Affiliated Hospital of Guangxi Medical University from August 2012 to October 2020 were retrospectively analyzed to provide the basic data for prevention and treatment of HPV infection.A total of 20 736 cases were divided into Han nationality group(n=16 390 cases)and Zhuang nationality group(n=4 346 cases). Polymerase chain reaction(PCR)was used to detect HPV type 21 and analyze the epidemiological characteristics of cervical HPV in women of different ethnic groups in this area.Results:In the 20, 736 cases, the proportion of positive HPV was 27.0%(5 591/20, 736). Among them, positive HPV accounted for 27.7%(4 536)in the Han group, and 24.3%(1 055)in Zhuang group, which were statistically significant( χ2=20.17, P<0.01). Peak age of infection in Zhuang women was more than 65 years.The most common HPV genotypes in both ethnics groups in Guangxi were HPV 16, 52, 58, 18, and 53.In women with positive HPV, the constituent ratio of HPV16 and HPV 52 rose with age ageing, while constituent ratio of HPV 6 and 11 presented the opposite trend. Conclusions:The HPV and HR(high-risk)-HPV positive composition ratio is lower in Zhuang women than in Han women in Guangxi.Among Han and Zhuang females, HPV 16, 52, 58, 18 and 53 have the highest positive composition ratio.HPV genotyping shows an age-increasing change.