Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry* ; Sesquiterpenes/chemical synthesis* ; Molecular Structure ; Humans ; Liver Cirrhosis/genetics* ; Biomimetics ; Plant Extracts/pharmacology*

Objective To explore the effect of phloretin on the proliferation,apoptosis,and tumorigenicity of ovarian cancer cells by regu-lating the Rac1/Akt/NF-κB signaling pathway.Methods The ovarian cancer cell line SKOV3 and the human normal ovarian epithelial cell line IOSE-80 were divided into the following groups:control,low-dose phloretin,medium-dose phloretin,high-dose phloretin,PM A,and high-dose phloretin+PMA.Morphological changes were observed under a microscope.Cell viability and apoptosis were assessed using the CCK-8 assay,colony formation assay,and flow cytometry.Western blotting was performed to detect the expression of proteins related to the Rac1/Akt/NF-κB signaling pathway.Tumor-bearing nude mice were established,tumor weights were measured,and the expres-sion levels of Rae1 and Akt in tumor tissues were analyzed.Results Compared with the control group,SKOV3 cells treated with low-,medium-,and high-dose phloretin showed reduced survival rate,colony formation,and expression of p-NF-κB p65/NF-κB p65,p-Akt/Akt,and Rac 1 in a dose-dependent manner.However,PM A reversed the inhibitory effects of high-dose phloretin on the malignant progression of ovarian cancer.In vivo experiments demonstrated that phloretin significantly inhibited tumor growth and reduced Akt and Rae1 expres-sion in tumor tissues(P＜0.05).Conclusion Phloretin suppresses the malignant progression of ovarian cancer by inhibiting the Rae1/Akt/NF-κB signaling pathway.

Objective To explore the effect of phloretin on the proliferation,apoptosis,and tumorigenicity of ovarian cancer cells by regu-lating the Rac1/Akt/NF-κB signaling pathway.Methods The ovarian cancer cell line SKOV3 and the human normal ovarian epithelial cell line IOSE-80 were divided into the following groups:control,low-dose phloretin,medium-dose phloretin,high-dose phloretin,PM A,and high-dose phloretin+PMA.Morphological changes were observed under a microscope.Cell viability and apoptosis were assessed using the CCK-8 assay,colony formation assay,and flow cytometry.Western blotting was performed to detect the expression of proteins related to the Rac1/Akt/NF-κB signaling pathway.Tumor-bearing nude mice were established,tumor weights were measured,and the expres-sion levels of Rae1 and Akt in tumor tissues were analyzed.Results Compared with the control group,SKOV3 cells treated with low-,medium-,and high-dose phloretin showed reduced survival rate,colony formation,and expression of p-NF-κB p65/NF-κB p65,p-Akt/Akt,and Rac 1 in a dose-dependent manner.However,PM A reversed the inhibitory effects of high-dose phloretin on the malignant progression of ovarian cancer.In vivo experiments demonstrated that phloretin significantly inhibited tumor growth and reduced Akt and Rae1 expres-sion in tumor tissues(P＜0.05).Conclusion Phloretin suppresses the malignant progression of ovarian cancer by inhibiting the Rae1/Akt/NF-κB signaling pathway.

ObjectiveTo explore the mental health status and its influencing factors among middle school students in Xide County， Liangshan Yi Autonomous Prefecture， and to provide references for mental health interventions for local middle school students. MethodsUsing a cross-sectional study design， one junior middle school and one senior middle school in Xide County， Liangshan Prefecture， Sichuan Province， were randomly selected on September 16， 2021， and two classes per grade in each school involving 288 students were recruited. Subjects were assessed using Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， Generalized Anxiety Disorder Scale-7 item （GAD-7）， PTSD Checklist for DSM-5 （PCL-5）， Multidimensional Scale of Perceived Social Support （MSPSS） and UCLA Loneliness Scale （ULS-3）. Then the scores of above scales were compared among middle school students with different demographic characteristics， and binary Logistic regression analysis was conducted to screen the influencing factors of post-traumatic stress disorder (PTSD） symptoms. ResultsAmong the respondents， 17.71% （95% CI： 0.133~0.221）， 8.68% （95% CI： 0.054~0.120）， 2.78% （95% CI： 0.009~0.047） and 45.83% （95% CI： 0.400~0.516） were reported to have symptoms of depression， anxiety， PTSD and loneliness， respectively. Students in senior middle school scored lower on PCL-5 and ULS-3 than those in junior middle school ［（6.46±8.91） vs. （8.87±9.42）， t=2.202， P<0.05； （4.67±1.65） vs. （5.60±1.88）， t=4.431， P<0.01］. Regression analysis denoted that depressive symptoms （OR=7.630， P<0.05） and anxiety symptoms （OR=3.789， P<0.01） were risk factors for PTSD symptoms among middle school students. ConclusionThe middle school students in Xide County， Liangshan Yi Autonomous Prefecture suffer a high prevalence rate of depressive symptoms and loneliness， and those in junior middle school are more likely to feel a sense of strong loneliness， furthermore， depressive symptoms and anxiety symptoms are risk factors for PTSD symptoms.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC₅₀ values of 34.89 and 19.88 μmol·L^-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC₅₀ values of 32.67, 79.38, and 16.74 μmol·L^-1, respectively.
Flavonoids/chemistry* ; SARS-CoV-2 ; Rhizome ; COVID-19 ; Peptide Hydrolases ; Antiviral Agents/chemistry*

Objective: To understand vulnerability to psychological crisis among rural college students and its related factors, so as to provide reference for the prevention or intervention of psychological crisis among rural college students. Methods: A total of 3 560 rural college students from grade one to grade three from five universities were selected using convenient cluster sampling method from January to September 2022 in Nanyang City. General information, vulnerability to psychological crisis, parenting style and Scale of Perceived Social Self efficacy (PSSE) were collected and analyzed through questionnaire. Results: Among the investigated rule college students, the score of psychological crisis vulnerability and spoiling dimension of parenting style were (10.76± 3.46 ) points and (2.68±0.55) points, while the score of trust encouragement dimension of parenting style and PSSE were (2.52± 0.62 ) points and (3.29±0.61) points. Pearson correlation analysis showed that vulnerability to psychological crisis of rural students was positively correlated with spoiling and neglect ( r =0.32, 0.49), and was negatively correlated with trust encouragement, emotional warmth and PSSE ( r =-0.38, -0.53, -0.51)( P <0.05). Multiple linear regression analysis revealed that single parent family or other families, poor students, left behind experience, high score of spoiling and high score of neglect revealed high psychological crisis vulnerability ( P <0.05). High score of trust encouragement, high score of emotional warmth and PSSE were associated with low vulnerability to psychological crisis ( P <0.05). Conclusion Vulnerability to psychological crisis among rural college students is higher, which is related to the family structure, students whether they are poor, leftover experience, parenting style and PSSE. Mental health among rural college students should be promoted by strengthening communication with students parents and cultivating students social self efficacy.

BACKGROUND: This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis. METHODS: First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system. RESULTS: A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011). CONCLUSION The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.
Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/genetics* ; Silicosis/genetics*

To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort, we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments. Records of patients with primary complaint of throat discomfort, absence of chest pain at onset, and an ultimate diagnosis of acute coronary syndrome, as well as patients with pharyngitis (as controls) were collected from May 2015 to April 2016. The patients' main manifestations were compared. Logistic regression results showed that chest tightness, dyspnea, perspiring, and exertional throat symptoms were significantly associated with acute coronary syndrome, with odds ratios of 8.3 (95% CI 2.2-31.5), 10.9 (95% CI 1.8-66.9), 25.4 (95% CI 3.6-179.9), and 81.2 (95% CI 13.0-506.7). A total of 25 (56.82%) out of 44 acute coronary syndrome patients, who were first admitted to the otorhinolaryngology department, were misdiagnosed, with a 12% (3/25) mortality rate. Throat discomfort can be the principal manifestation of acute coronary syndrome. Such patients exhibit high misdiagnosis and mortality rates. Exertional throat symptoms, chest tightness, perspiring, and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort. The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.
Acute Coronary Syndrome/etiology* ; Dyspnea/etiology* ; Humans ; Pharyngitis/diagnosis* ; Pharynx ; Retrospective Studies

OBJECTIVE To investigate the antibacterial activities of flavaspidic acid BB against the main pathogens of skin and soft tissue infections such as methicillin -resistant Staphylococcus aureus （MRSA）and methicillin -sensitive Staphylococcus aureus （MSSA） in vitro and in vivo . METHODS Microdilution method was used to determine the minimum inhibitory concentration（MIC）and minimum bactericidal concentration （MBC）of flavaspidic acid BB on 10 strains of MRSA and 13 strains of MSSA ；time-kill curves of MRSA 11 and MSSA 23 strains were drawn by plate method ；the checkerboard dilution method was used to determine the combined antibacterial effect of flavaspidic acid BB and mupirocin ；the skin abscess model of mice was established to evaluate the antibacterial effects of 0.5%，1%，2% flavaspidic acid BB cream on MRSA 11 or MSSA 23 strains in vivo；scanning electron microscopy was used to observe the effects of flavaspidic acid BB on the morphology of MRSA 11 or MSSA23 strains. The contents of nucleic acid leakage and extracellular protein were also determined . RESULTS MIC and MBC ranges of flavaspidic acid BB against 10 strains of MRSA were 6.30-80.00 μg/mL and 40.00-640.00 μg/mL；MIC and MBC ranges of 13 strains of MSSA were 40.00-80.00 μg/mL and 63.50-126.99 μg/mL，respectively. The bactericidal rate of MRSA 11 and MSSA23 strains were 99.9% after interfered with plavaspidic acid BB for 36 h. The combination of flavaspidic acid BB and mupirocin showed an additive effect on MRSA strain and an additive or synergistic effect on MSSA strain . The 0.5%，1% and 2% flavaspidic acid BB cream could reduce the volume of abscess and the bacterial load of skin abscess model mice to some extent （P＜0.05），and improved the pathological changes of skin inflammation in skin abscess site of mice . Flavaspidic acid BB could make MRSA 11 and MSSA 23 cells shrinkage and rupture ，and significantly increase the contents of nucleic acid leakage and extracellular protein （P＜0.01）. CONCLUSIONS Flavaspidicacid BB shows good antibacterial effect on MRSA and MSSAE-mail：tchp66@163.com in vitro and in vivo ，the mechanism of which may be related to the change of membrane permeability .

OBJECTIVE To study the effects of yunaconitine on myocardial injury in rats and its mechanism related to mitochondrial apoptosis pathway rats. METHODS Forty SD rats were divided into normal group （normal saline）， yunaconitine high-dose and low-dose groups（0.14， 0.09 mg/kg）and aconitine group （positive control， 0.88 mg/kg） by random number method， with 10 rats in each group. They were given relevant medicine intragastrically， once a day， for consecutive 7 days. The levels of lactate dehydrogenase （LDH）， creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， superoxide dismutase （SOD） and malondialdehyde （MDA） in serum as well as the level of reactive oxygen species （ROS） in myocardial tissue were detected. The pathomorphological changes of myocardium and ultrastructural changes of myocardial mitochondria were all observed. The apoptosis of cardiomyocytes was determined. The protein relative expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 were determined in myocardium of rats. RESULTS Compared with normal group， the serum levels of LDH， CK， CK-MB and MDA， the apoptotic numbers of cardiomyocytes， the level of ROS and protein expression of caspase-3 in myocardium were increased significantly in yunaconitine high-dose and low- dose groups （P＜0.05 or P＜0.01）； serum level of SOD and Bcl-2/Bax ratio in myocardium were all decreased significantly （P＜ 0.01）； the protein relative expressions of caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 in myocardium were significantly increased in yunaconitine high-dose group （P＜0.05）； some pathomorphological changes were found in 2 groups， such as myocardial fiber disorder， mitochondrial swelling. CONCLUSIONS Yunacotine could cause myocardial injury in rats. Its mechanism might be related to destroying the integrity of cardiomyocyte membrane， causing oxidative stress of cardiomyocyte， and inducing the apoptosis of myocardial cells through mitochondrial pathway.