Seven novel acylphloroglucinol-sesquiterpenoid adducts, designated as dryatraols J-P (1-7), were isolated from the rhizomes of Dryopteris atrata (Wall. ex Kunze) Ching. The structures, including absolute configurations, were elucidated using comprehensive spectroscopic data, calculated ¹³C Nuclear Magnetic Resonance-Diastereotopic Probability Assignment Plus (¹³C NMR-DP4+) probability analysis, and ECD calculations. These structures represent a rare subclass of carbon skeleton of acylphloroglucinol-sesquiterpenoid adducts with a furan ring connecting the acylphloroglucinol and sesquiterpenoid moieties. Notably, compounds 1-6 are the first reported examples of acylphloroglucinol-sesquiterpenoid adducts with dimeric acylphloroglucinol incorporated into the aristolane- or rulepidanol-type sesquiterpene, while compound 7 features a hydroxylated monomeric acylphloroglucinol motif. A preliminary evaluation of their antiviral activities revealed that compounds 1-6 exhibited more potent activities against respiratory syncytial virus (RSV) with IC₅₀ values ranging from 0.75 to 3.12 μmol·L^-1 compared to the positive control (ribavirin).
Antiviral Agents/isolation & purification* ; Phloroglucinol/isolation & purification* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Dryopteris/chemistry* ; Respiratory Syncytial Viruses/drug effects* ; Humans ; Rhizome/chemistry* ; Drugs, Chinese Herbal/pharmacology*

Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC₅₀ 5.01 ± 0.14 μmol·L^-1) surpassed that of the positive control (ribavirin, IC₅₀ 6.23 ± 0.95 μmol·L^-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification* ; Tryptamines/isolation & purification* ; Peganum/chemistry* ; Seeds/chemistry* ; Alkaloids/isolation & purification* ; Molecular Structure ; Humans ; Respiratory Syncytial Viruses/drug effects* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/pharmacology*

Objective To explore the effect of 12-week simplified Tai Chi training on rehabilitation and neuromuscular control in individuals with chronic ankle instability(CAI).Methods Thirty-four partic-ipants with CAI were randomly divided into an experimental group and a control group,each of 17.The control group received 12-week health education,while the experimental group underwent simpli-fied Tai Chi training for the same length.Before and after the intervention,both groups were evaluat-ed their self-reported instability feeling,ankle muscle strength,proprioception and dynamic postural stability.Results After intervention,a significant increase was observed in the average Cumberland An-kle Instability Tool(CAIT),the maximum extension distance in the posteromedial and posterolateral di-rections of the modified Star Excursion Balance Test(mSEBT)in,as well as the ankle peak torque in plantarflexion,inversion and eversion(P<0.05)in the experimental.Moreover,the ankle passive motion proprioceptive threshold in plantarflexion and inversion decreased significantly in the experimental group after intervention(P<0.05).Meanwhile,after intervention,the average CAIT score,maximum ex-tension distances in the posteromedial and posterolateral directions in the mSEBT,and the ankle peak torques in plantarflexion,inversion and eversion of the experimental group were significantly higher than the control group(P<0.05),while the ankle passive motion proprioceptive threshold in plantarflex-ion was significantly lower than the latter(P<0.05).Conclusion Twelve-week simplified Tai Chi train-ing can improve the clinical subjective instability of CAI participants,maybe related to the improve-ment of ankle muscle strength,proprioception and dynamic postural stability.Therefore,it is suggest-ed that simplified Tai Chi should be one of the rehabilitation methods for CAI patients.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective To explore the effects of two methods of video laryngoscope insertion on the success rate of tracheal intubation and postoperative pharyngeal complications.Methods We selected 80 elective surgerypatients with American Society of Anesthesiologists(ASA)classification Ⅰ to Ⅱ who had no difficult airway in preoperative assessment under general anesthesia with orotracheal intubation.They were aged 18 to 65 years old and there were no restrictions on height and weight.The patients were randomly divided into a group with laryngoscope inserted through the middle of the mouth(group M)and a group with laryngoscope inserted through the right corner of the mouth(group C),with 40 cases in each group.Observe the laryngoscope exposure grading,oropharyngeal mucosal bleeding,first-time intubation success rate,and occurrence of pharyngeal pain and hoarseness within 48 hours after surgery in both groups;record the patients'systolic blood pressure(SBP),diastolic blood pressure(DBP),and heart rate(HR)among admission to the room(T0),after giving anesthesia drugs(T1),immediately after intubation(T2),1 min after intubation(T3),and 3 min after intubation(T4).Results The SBP of group M was lower than that of group C at T3(P＜0.05);There was no statistically significant difference in laryngoscope exposure grading between the two groups(P＞0.05).The intubation time,oropharynx mucosal bleeding and the cases of sore throat within 48 hours of group M were less than those in group C(P＜0.05).The success rate of primary intubation in group M was higher than that in group C(P＜0.05).Conclusion Inserting a video laryngoscope through the middle of the mouth can reduce oropharyngeal mucosal bleeding,improve the success rate of intubation,and reduce the incidence of postoperative pharyngeal complications.

Objective To investigate the predictive value of color Doppler ultrasound parameters for fetal growth restriction (FGR) induced by hypertensive disorders of pregnancy in high-altitude regions. Methods Pregnant women with gestational hypertension who were treated between July 2020 and June 2022 at the Affiliated Hospital of Qinghai University (with altitude of 2, 300 meters, were divided into group A1 with 19 cases and group A2 with 51 cases according to occurrence of FGR), Yushu People's Hospital (with altitude of 3, 700 meters, were divided into group B1 with 25 cases and group B2 with 47 cases according to occurrence of FGR), and Civil Aviation Clinical Medical College of Peking University (plain region, control group with 71 cases) were enrolled in this study. All pregnant women in each group underwent fetal color Doppler ultrasound examination of the middle cerebral artery (MCA) and umbilical artery (UA) blood flow parameters, including pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D), peak systolicvelocity (PSV), and cerebroplacental ratio (CPR) at 28 weeks of gestation were detected. Multivariate Logistic regression analysis was performed to identify independent risk factors for FGR in pregnant women with gestational hypertension. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of color Doppler parametersfor FGR. Results The UA blood flow parameters (PI, RI, S/D, PSV) of the fetuses in groups A1, A2, B1, and B2 were significantly higher than those in the control group, while the MCA blood flow parameters (PI, RI, S/D, PSV) and CPR were significantly lower (P < 0.05). Among the five groups, group B1 had the highest UA blood flow parameters (PI, RI, S/D, PSV) and the lowest MCA blood flow parameters (PI, RI, S/D, PSV) and CPR (P < 0.05). Multivariate Logistic regression analysis revealed that high altitude of residence and umbilical cord abnormalities were independent risk factors for FGR in pregnant women with gestational hypertension (P < 0.05). ROC curve analysis showed that the areas under the curves for the combined prediction of FGR in pregnant women with gestational hypertension at altitudes of 2, 300 meters and 3, 700 meters using color Doppler multi-parameters were 0.906 and 0.917, respectively, indicating a significantly higher predictive performance compared to individual parameter (P < 0.05). Conclusion Color Doppler ultrasound parameters of UA and MCA bloodflow during the second trimester of pregnancy demonstrate good predictive value for FGR induced by hypertensive disorders of pregnancy in high-altitude regions at different altitudes, and the predictive performance is even higher when multiple parameters are combined.

Objective To explore the diagnostic value of color Doppler ultrasound for fetal intrauterine distress(FIUD)in high-risk puerperae in plateau areas.Methods A total of 130 puerperae in plateau areas and 130 puerperae in plain areas were enrolled.According to presence or absence of FIUD in different areas,they were divided into the plateau distress group(47 cases),the plateau normal group(83 cases),the plain distress group(31 cases)and the plain normal group(99 cases).All cases underwent blood flow detection of middle cerebral artery(MCA)and umbilical artery(UA)before delivery,and cerebral-placental ratio(CPR)was calculated.The incidence of FIUD was compared between high-risk puerperae in plateau area and in plain area.Gestational age,birth weight,cesarean section rate and blood spectrum parameters of MCA and UA were compared between the four groups.The predictive value of color Doppler ultrasound parameters for FIUD was analyzed by receiver operating characteristic(ROC)curves.Results The incidence rates of FIUD and severe FIUD were higher in patients of plateau areas than those in plain areas(36.15%,13.85%vs.23.85%,4.62%,P＜0.05).Compared with the plateau distress group,gestational age and birth weight were increased in the plateau normal group and the plain distress group(P＜0.05).Compared with the plateau distress group,PI,RI,S/D and CPR of MCA were increased,while PI,RI and S/D of UA were decreased in the plateau normal group and the plain distress group(P＜0.05).Results of ROC curve analysis showed that overall performance advantage of S/D of UA was the most obvious in the diagnosis of FIUD in high-risk puerperae in plateau areas.The diagnostic sensitivity of RI of MCA was the highest,and the diagnostic specificity of CPR was the highest(P＜0.05).Conclusion Color Doppler ultrasound has good diagnostic value for FIUD in high-risk puerperae in plateau areas,which can be applied as an effective clinical screening means for FIUD.

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metab-olomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of devel-oping SMDCs for precise cancer therapy.

Cervical incompetence is a common cause of late abortion and premature birth, which can be effectively treated by cervical cerclage. Controversy remains on the timing and perioperative management of cervical cerclage based on different indications. This paper briefly reviews the current differences and debates and elaborates some opinions regarding cervical cerclage in order to provide a reference for clinical decision-making and research.

Objective:The aim of this study was to explore the associations of muscle size and density with handgrip strength(HGS)and the Timed Up and Go(TUG)test.Methods:Totally 301 participants living in the Xinjiekou community near Beijing Jishuitan Hospital were recruited for CT imaging of the hip and a 1-cm slice of the mid-thigh.The cross-sectional area and density of the gluteus maximus and the mid-thigh muscles were estimated by the Osirix viewer based on CT images.HGS and TUG were also performed in these subjects.Logistic regression analysis was used to evaluate the correlations of muscle density and size with TUG and grip strength.Results:In women, after adjustment for age and BMI, the density of the gluteus maximus was negatively correlated with TUG( P trend=0.0366), while the size of the gluteus maximus and the mid-thigh muscles was not correlated with TUG.In men, the density or size of these muscles was not correlated with TUG.After adjustment for age and BMI, the density of the gluteus maximus was positively correlated with grip strength( P trend=0.0334)and the size of the mid-thigh muscles was also positively correlated with grip strength( P trend=0.0155)in men, but they were not correlated with grip strength in women. Conclusions:There were sex differences in the relationship between muscle size or density and grip strength or timed up and go.The density of the gluteus maximus is associated with muscle strength and physical performance while the size of the mid-thigh muscles is correlated with muscle strength.