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 evaluate the influence of electronic sports games on children s acquisition of basic motor skills, so as to provide assistance for childrens acquisition of basic motor skills in the context of digital society. Methods: Computer searches were conducted on CNKI, Web of Science, Cochrane Library and PubMed databases from March 2012 to March 2022. Methodological quality of included studies was evaluated using the Cochrane bias risk assessment tool RoB 2 and the extension tools RoB 2 Cluster and ROBINS-I. Publication bias assessment, heterogeneity test, subgroup analysis and Meta analysis were performed using RevMan 5.3. Results: A total of 12 studies included 897 participants, 7 randomized controlled trials, 2 cohort randomized controlled trials and 3 non randomized trials. Among them, 2 items had a low risk of bias, 8 items had certain risks and 2 items had a high risk of bias. Measures of basic motor skills in children from 12 studies included object control skills, motor skills, coordination, agility and balance. The results of Meta analysis showed that electronic sports games had a positive effect on children s acquisition of basic motor skills ( SMD=0.81, 95%CI=0.46-1.17, P <0.05). Conclusion Children can generate positive interactive communication behavior through physical activity and digital screen, and then promote the development of basic motor skills.

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 improvement effect of myricitrin on bone defect in rats with bacterial osteomyelitis(OM)through vascular endothelial growth factor A(VEGFA)/stromal cell-derived factor(SDF-1)/C-X-C chemokine receptor 4(CXCR4)pathway.Methods Rats were randomly divided into the sham operation group,the OM group,the myricitrin group[50 mg/(kg·d)],PX-478 group[25 mg/(kg·d)VEGFA/SDF-1/CXCR4 signaling pathway inhibitor PX-478],and the myricitrin+PX-478 group[50 mg/(kg·d)myricitrin and 25 mg/(kg·d)PX-478],18 mice per group.Bilateral proximal tibia bone defects were used to construct bacterial OM rat model.After 12 weeks of continuous treatment,the wound healing degree of rats was observed,and anal temperature of rats was measured.The serum inflammatory factors interleukin(IL)-6,IL-1β,IL-17 and bone metabolism indexes bone alkaline phosphatase(BALP),osteocalcin(BGP)and C-terminal telopeptide of type Ⅰ collagen(CTX-Ⅰ)were measured by enzyma-linked immunosorbent assay(ELISA).The bacterial load of tissue around the lesion was detected.HE staining was used to detect the pathological changes of the tissue around lesions.The expression of CD31 was detected by immunofluorescence staining.Western blot assay was used to detect the expression of VEGFA/SDF-1/CXCR4 signal pathway related proteins.Results Compared with the sham operation group,the number of rats with grade A wound healing,BALP and BGP levels,CD31 positive area,VEGFA,SDF-1 and CXCR4 protein levels were decreased in the OM group(P＜0.005 or P＜0.05),and the anal temperature,bacterial load,IL-6,IL-1β,IL-17 and CTX-Ⅰlevels were increased(P＜0.05).Compared with the OM group,the BALP and BGP levels,CD31 positive area,VEGFA,SDF-1 and CXCR4 protein levels were increased,and the anal temperature,bacterial load,IL-6,IL-1β,IL-17 and CTX-Ⅰlevels were decreased in the myricitrin group(P＜0.05).Results of PX-478 group showed the opposite trend.PX-478 reversed the effect of myricitrin on the improvement of bone defects in bacterial OM rats.Conclusion Myricitrin may improve bone defect of OM rats by activating the VEGFA/SDF-1/CXCR4 signal pathway.

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.

ObjectiveTo observe the clinical efficacy of Feining Paidu decoction on refractory Mycoplasma pneumoniae pneumonia in child patients. MethodA randomized controlled trial （RCT） was conducted， with 96 child patients randomly divided into a control group and an observation group， each containing 48 cases. The control group received intravenous azithromycin （10 mg·kg^-1·d^-1） for 7 days， intravenous methylprednisolone （1 mg·kg^-1·d^-1） for 3 days， along with supportive treatments such as fluid infusion and antipyretics. The observation group received oral administration of Feining Paidu decoction once a day for 7 days. Changes in traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， serum soluble B7-H3 （sB7-H3）， serum inflammatory factors， coagulation function， and lung imaging ［computer tomography（CT）］ scores were observed in both groups. Adverse reaction events were also recorded. ResultThe total effective rate in the observation group was 95.74% （45/47）， significantly higher than 80.43% （37/46） in the control group （Z=-3.702， P<0.01）. Compared with the results before treatment， TCM syndrome scores， lung imaging scores， sB7-H3， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， D-dimer （D-D）， and fibrinogen （FIB） levels in both groups all significantly decreased after treatment （P<0.05， P<0.01）. After treatment， the observation group showed significantly better results in these indicators than the control group （P<0.05， P<0.01）. There was no statistically significant difference in thrombin time （TT） in the control group before and after treatment， while the observation group showed a significant prolongation after treatment （P<0.05）. There were no statistically significant differences in activated partial thromboplastin time （APTT） and prothrombin time （PT） between the two groups before treatment， and no serious adverse reactions occurred in either group. ConclusionFeining Paidu decoction combined with conventional treatment can alleviate inflammatory responses， improve hypercoagulable states， promote the absorption of pulmonary inflammation， and enhance the clinical efficacy of refractory Mycoplasma pneumoniae pneumonia in children.