Effects of different traditional Chinese exercise in the treatment of essential hypertension: a systematic review and network meta-analysis.

Background: As a therapy to prevent and treat essential hypertension (EH), traditional Chinese exercises (TCEs) were widely used in clinical practice. However, there is a lack of strictly comparison of the antihypertensive efficacy of different TCEs, which not conducive to the selection of the best and most optimal treatment. This study aimed to perform a network meta-analysis to objectively evaluate which TCE has the best effects in assisting with lowering blood pressure. Methods: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), VIP, SinoMed and Wanfang Data were searched for all randomized controlled trials (RCTs) on TCEs for the treatment of EH published up to July 10, 2023. RoB2.0 tool was utilized to evaluate the quality of the RCTs. The network meta-analysis was performed by R 4.1.2 and Stata 17.0. Weighted mean difference (WMD) was calculated for continuous outcomes. Results: A total of 29 studies, including 2,268 patients were included to analyze 6 different interventions. The network meta-analysis results presented that in comparison with control group, Tai Chi + antihypertensive medication [WMD = -10.18, 95% CI, (-14.94, -5.44)] is the most effective intervention for lowering systolic blood pressure (SBP), and Wuqinxi + antihypertensive medication [WMD = -10.36, 95% CI (-18.98, -1.66)] is the most effective intervention for lowering diastolic blood pressure (DBP). Conclusion: TCEs combined with antihypertensive medication may be able to achieve more prominent antihypertensive effects with Tai Chi and Wuqinxi potentially being the higher-priority options. However, well-designed randomized studies are warranted to further verify currently conclusion.

Ginsenoside Rb1 prevents age-related endothelial senescence by modulating SIRT1/caveolin-1/enos signaling pathway.

Background: Advancing age is one of the independent risk factors for cardiovascular disorders. The Compendium of Materia Medica, a classic book on traditional Chinese medicine, states that ginseng "harmonizes the five internal organs, calming the spirit and prolonging the years of life." Considered one of the primary bioactive compounds derived from Panax ginseng, ginsenoside Rb1 (g-Rb1) has been scientifically suggested to possess anti-senescence efficacy. More research is needed to explore the vascular pharmacological activity and potential clinical application value of g-Rb1. Aims of the study: Our previous study demonstrated that g-Rb1 could mitigate cellular senescence via the SIRT1/eNOS pathway. This study was performed to explore the exact mechanisms by which g-Rb1 modulates the SIRT1/eNOS pathway. Materials and methods: We used human primary umbilical vein endothelial cells (HUVECs) to establish a replicative ageing model. Real-time (RT‒PCR), western blotting, small interfering RNA (siRNA), and immunoprecipitation were conducted to detect the effect of g-Rb1 on the SIRT1/caveolin-1/eNOS axis. Results: G-Rb1 increased NO production and alleviated replicative senescence of HUVECs. The application of g-Rb1 elevated the mRNA and protein abundance of both SIRT1 and eNOS while concomitantly suppressing the expression of caveolin-1. Inhibition of SIRT1 and eNOS by siRNAs suppressed the anti-senescence function of g-Rb1, while caveolin-1 siRNA could enhance it. G-Rb1 decreased the acetylation level of caveolin-1 and increased NO production, which was suppressed by SIRT1 siRNA. Both g-Rb1 and caveolin-1 siRNA could reduce the acetylation level of eNOS and increase NO production. Conclusion: G-Rb1 prevents age-related endothelial senescence by modulating the SIRT1/caveolin-1/eNOS signaling pathway.

Nonpharmacological Therapies for Musculoskeletal Injury in Military Personnel: A Systematic Review/Meta-Analysis.

INTRODUCTION: Musculoskeletal (MSK) injury is an inherent risk for military personnel that can potentially impact job performance, productivity, and military readiness. Evidence is needed to show the efficacy of nonpharmacological, self-managed therapies to reduce MSK symptoms at common injury sites that are feasible for use during expeditionary operations and home stations. This systematic review and meta-analysis identified, summarized, and synthesized available evidence from randomized and non-randomized trials on the effectiveness of self-managed, home-use therapies to improve pain, muscle strength, and physical performance in military personnel with MSK injuries, when compared to controls. METHODS: The electronic databases of MEDLINE ALL Ovid, Embase.com, Cochrane Library, Scopus, Clinicaltrial.gov, and CINAHL Complete via EBSCO were systematically searched for relevant reports published in English. Utilizing the Covidence platform and consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, multiple reviewers, using pre-determined data fields, screened for eligibility, assessed risk of bias (RoB), and performed data extraction. Evaluation of treatment effectiveness was determined using multilevel mixed-effects meta-analysis. RESULTS: The database and register search yielded 1,643 reports that were screened for eligibility. After screening of titles/abstracts and full texts, 21 reports were identified for evidence synthesis. Of these, two reports were excluded and two described the same study, resulting in a final list of 18 studies (19 reports). For quality assessment, the overall RoB for the 18 studies was categorized as 33.3% low risk, 55.6% with some concerns, and 11.1% high risk. Across the five domains of bias, 70% of the reports were classified as low risk. This systematic review found that the differences in interventions, outcome measures, and design between the studies were associated with a substantial degree of heterogeneity (I2 = 60.74%), with a small overall improvement in outcomes of the interventions relative to their specific control (standard mean difference 0.28; 95% CI, 0.12 to 0.45). There were varying degrees of heterogeneity for individual body regions. This was due, in part, to a small number of studies per bodily location and differences in the study designs. For the neck/shoulder, heterogeneity was moderate, with the clearest positive effect being for physical performance outcomes via other medical devices. For the back, there was substantial heterogeneity between studies, with modest evidence that pain was favorably improved by other medical devices and exercise interventions. For the leg, one study showed a clear large effect for other medical devices (shockwave treatment) on pain with substantial heterogeneity. The best evidence for positive effects was for the knee, with mainly negligible heterogeneity and some benefits from bracing, electrotherapy, and exercise. CONCLUSION: Evidence showed small beneficial effects in pain, strength, and physical performance by individual body regions for some interventions, compared to controls. The best evidence for a positive effect was for the knee. The findings suggest that some benefit may be obtained by including several treatments during deployment in austere environments and prolonged casualty care scenarios of military personnel with MSK injuries. Further research is warranted to better assess the potential benefits of using these treatments during deployments in austere environments as part of an individualized, multimodal approach for MSK injuries.

Hyperhenrones: Prenylated α-pyrones with anti-inflammatory activity from Hypericum henryi.

Fourteen previously undescribed α-pyrone derivatives (1-14) together with four known analogs (15-18) were isolated from a traditional Chinese medicinal plant Hypericum henryi. Compounds (+)/(-)-1, 2, and 3 share a rare 6/6/4/6/6 polycyclic skeleton. Compound 14 was the first example of a 7,7-dimethyl-pyran-4-one moiety. Their structures were elucidated using comprehensive spectroscopic analyses and electronic circular dichroism calculations. The anti-inflammatory activities of 1-18 were screened in lipopolysaccharide-induced RAW264.7 cells. Among them, compounds 14, (+)-18, and (-)-18 exhibited inhibitory effects against nitric oxide production in LPS-induced RAW264.7 cells. Additionally, compound 14 suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-induced RAW264.7 cells. Furthermore, preliminary mechanism studies indicated that compound 14 suppressed the phosphorylation and degradation of the inhibitor of NF-κB, and this led to the inhibition of NF-κB activation.

Screening and identification of antibacterial components in Artemisia argyi essential oil by TLC-direct bioautography combined with comprehensive 2D GC × GC-TOFMS.

One of the primary components that contribute to Artemisia argyi 's effectiveness is essential oil, which has an exceptional antibacterial effect that has been well documented. The actual cause of its antibacterial activity and associated mechanism, however, are still not completely understood. For the first time, comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (2D GC × GC-TOFMS) and thin-layer chromatography-direct bioautography (TLC-DB) were employed to investigate its antibacterial components. The antibacterial properties of A. argyi essential oil were investigated, and the antibacterial activity of six compounds was evaluated, using Staphylococcus aureus (S. aureus) and Escherichia coli (E. coil) as test microorganisms. TLC-direct bioautography was used to screen two bioactive clusters. Following 2D GC × GC-TOFMS identification of bioactive clusters, six compounds were evaluated for in vitro antibacterial activity verification. All the components tested displayed antibacterial action. Results showed that α-terpineol and eugenol had high potent antibacterial activity (MIC＜0.62 mg/mL, IC50＜2.00 mg/mL). For complex essential oils from traditional Chinese medicine, this method is efficient for quick screening and identifying antibacterial compounds.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

[Characteristics of Cadmium Concentration and Transport of Pueraria thornsonii in Farmland with Different Cadmium Pollution Degrees].

This study aimed to elucidate the cadmium (Cd) concentration and transport characteristics of Pueraria thornsonii in farmland with different Cd pollution degrees, so as to provide a reference basis for phytoremediation of Cd-contaminated farmland. The multi-point experiments in farmland with different Cd pollution degrees[ω(Cd) 0.32-38.08 mg·kg-1] were conducted, and the biomass (dry weight), Cd content, accumulation, concentration, and transport of Cd in P. thornsonii tissues under the main growing period were assessed. According to the results, for P. thornsonii, the tuber dry weight ranged from 5.04 to 11.98 t·hm-2, biomass ranged from 13.21 to 29.07 t·hm-2, and Cd accumulation ranged from 15.74 to 106.03 g·hm-2in the study area. The pattern of Cd uptake by P. thornsonii showed that the main vine>leaf>lateral branches>basal part of sti>tuber. The Cd content in P. thornsonii tissues considerably increased with soil Cd content (P<0.05), whereas the biomass decreased significantly (P<0.05). The Cd concentration and transport factor of aboveground parts in P. thornsonii showed a trend of initially falling, then increasing and decreasing again, whereas the Cd enrichment and transport coefficient of tubers gradually decreased. Correlation analysis revealed that the amount of Cd in the soil was a major predictor of Cd accumulation in P. thornsonii. Under light to moderate Cd contamination, the commercial portion of P. thornsonii (arrowroot)[ω(Cd) 0.03-0.22 mg·kg-1] was less than the standard limit for medicinal plants (≤ 0.30 mg·kg-1). In P. thornsonii from moderately contaminated areas, the Cd concentration and transport factor of aboveground parts were 2.43-7.97 and 3.02-9.81, respectively. This indicates that P. thornsonii is a prospective plant ideal for remediating Cd-contaminated soil because of its high capacity to transfer and enrich Cd.

Clinical study of acupuncture combined with surface anesthesia using proparacaine in geriatric cataract phacoemulsification.

BACKGROUND: During anesthesia administration for cataract surgery, low pH of proparacaine may induce pain or complications such as corneal damage and poor wound healing, with the use of additional drops intraoperatively increasing the risk of complications. Accordingly, there is a clinical need for adjuncts to local anesthesia needs to improve the efficiency of anesthesia and reduce the required amount of intraoperative proparacaine. AIM: To identify a method of anesthesia for geriatric cataract phacoemulsification that provides more efficient analgesia and improves clinical efficacy. METHODS: A total of 130 geriatric patients with cataracts who attended Hebei Eye Hospital from December 2020 to December 2022 were included in the present study. Patients were divided into the proparacaine surface anesthesia (SA) group (65 cases) and the compound acupuncture-medicine anesthesia group (CAMA group, 65 cases). Patients in the CAMA group were provided acupuncture analgesia in addition to SA. Preoperative anxiety [Self-Rating Anxiety Scale (SAS) score and state anxiety inventory (SAI) score], intraoperative stress, vital signs, analgesia, and cooperation, as well as postoperative adverse events, were compared between groups. RESULTS: More marked reductions in anxiety were observed among patients in the CAMA group, with corresponding reductions in SAS and SAI scores. During the operation, no change in the secretion of E, NE, or Cor group compared to the preoperative period was observed in the CAMA, which was markedly lower than that in the SA group. Heart rate, blood pressure, and respiratory rate were more stable intraoperatively in the CAMA group. In addition, the incidence of intraoperative pain and the number of additional doses of anesthesia required in the CAMA group were markedly lower than in the SA group. Accordingly, patients in the CAMA group were able to avoid eye movements and eyelid closing leading to greater cooperation with surgeons during surgery. Furthermore, marked reductions in intraoperative adverse effects were observed in the CAMA group, indicating greater overall safety. CONCLUSION: Proparacaine SA combined with acupuncture as an analgesic provides improved analgesia with greater safety compared to surface anesthesia with proparacaine during geriatric cataract phacoemulsification.

Complete chloroplast genome data of Ranunculus membranaceus (Ranunculaceae), an important medicinal plant species.

The perennial alpine herb Ranunculus membranaceus (Ranunculaceae) has significant medicinal value. The complete chloroplast genome of R. membranaceus was sequenced by high-throughput Illumina sequencing Platform Illumina NovaSeq 6000. The circular genome is 156,028 bp in size, including two inverted repeats (IRs) of 25,361 bp, a large single-copy (LSC) region of 85,491 bp, and a small single-copy (SSC) region of 19,815 bp. A total of 128 genes were annotated, namely 84 protein-coding genes (PCGs), 36 tRNA genes, and eight rRNA genes. Two phylogenetic trees of 18 species of the tribe Ranunculeae species were constructed with Meconopsis punicea as the outgroup based on the whole chloroplast genomes and the concatenated sequence of PCGs, respectively. Phylogeny showed that R. membranaceus was closely related to R. yunnanensis. These data enrich knowledge of Ranunculaceae genetics and will contribute to further studies of R. membranaceus in molecular breeding, genetic transformation, species identification, genetic engineering and phylogenetic research.

[Acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy based on data mining technology].

OBJECTIVE: To analyze the acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy by data mining technology. METHODS: The literature regarding acupuncture and moxibustion for post-stroke epilepsy included in CNKI, VIP, Wanfang, SinoMed and PubMed databases from the establishment of the database to August 1st 2022 was retrieved. Microsoft Excel 2019 software was used to establish a database to conduct the descriptive analysis of acupoints; SPSS Modeler 18.0 Apriori algorithm was used to conduct association rule analysis; high-frequency acupoint co-occurrence network diagrams were drawn by Cytoscape3.9.0 software; SPSS Statistics 25.0 software was used to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn. RESULTS: Totally 39 articles were included, and 63 prescriptions of acupuncture and moxibustion were extracted, involving 56 acupoints, with a total frequency of 516 times; the top three acupoints with the highest frequency of use were Baihui (GV 20), Fenglong (ST 40) and Neiguan (PC 6); the selected meridians were mainly the governor vessel, the hand and foot yangming meridians; the selection of acupoints were mostly in the head, neck and lower limbs; in terms of acupoint compatibility, Hegu (LI 4)-Shuigou (GV 26) and Neiguan (PC 6) had the highest confidence degree; The top 20 high-frequency acupoints could be divided into 4 effective clusters. CONCLUSION: Modern acupuncture and moxibustion treatment for post-stroke epilepsy attaches great importance to the use of yang meridians and meridians with enrich qi and blood; the core prescription is Shuigou (GV 26)-Neiguan (PC 6)-Hegu (LI 4)-Baihui (GV 20). In addition, the combination of distant and near acupoints is highly valued to improve clinical efficacy.

Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: In the first interim analysis of the ORIENT-31 trial, compared with chemotherapy alone, sintilimab plus bevacizumab biosimilar IBI305 plus chemotherapy (pemetrexed and cisplatin) significantly improved progression-free survival in patients with EGFR-mutated non-squamous non-small-cell lung cancer (NSCLC) who progressed on EGFR tyrosine-kinase inhibitor treatment. However, the benefit of anti-PD-1 or PD-L1 antibody added to chemotherapy in this patient population remains unclear, with no prospective evidence from phase 3 trials globally. We report the results from the prespecified second interim analysis of progression-free survival between sintilimab plus chemotherapy and chemotherapy alone, the updated results of sintilimab plus IBI305 plus chemotherapy, and preliminary overall survival results. METHODS: This double-blind, randomised, placebo-controlled, phase 3 trial was done at 52 centres across China and included patients aged 18-75 years with locally advanced or metastatic (stage IIIB, IIIC, or IV according to the American Joint Committee on Cancer, eighth edition) EGFR-mutated non-squamous NSCLC, disease progression after EGFR tyrosine-kinase inhibitor treatment (according to the Response Evaluation Criteria in Solid Tumours version 1.1 [RECIST 1.1]), and at least one measurable lesion (according to RECIST 1.1). Patients were randomly assigned (1:1:1), using an interactive web response system, to receive sintilimab (200 mg) plus IBI305 (15 mg/kg) plus pemetrexed (500 mg/m2) and cisplatin (75 mg/m2), sintilimab plus chemotherapy, or chemotherapy alone on day 1 of each 3-week cycle for four cycles, followed by maintenance therapy of sintilimab, IBI305, and pemetrexed. All study drugs were administered intravenously. The primary endpoint was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee. Data cutoff was March 31, 2022, unless otherwise specified. The study is registered at ClinicalTrials.gov, NCT03802240 (ongoing). FINDINGS: Between July 11, 2019, and March 31, 2022, 1011 patients were screened and 476 were randomly assigned (158 to the sintilimab plus IBI305 plus chemotherapy group, 158 to the sintilimab plus chemotherapy group, and 160 to the chemotherapy alone group). The median follow-up duration for progression-free survival was 12·9 months (IQR 8·2-17·8) in the sintilimab plus IBI305 plus chemotherapy group, 15·1 months (8·0-19·5) in the sintilimab plus chemotherapy group, and 14·4 months (9·8-23·8) in the chemotherapy alone group. Sintilimab plus chemotherapy significantly improved progression-free survival compared with chemotherapy alone (median 5·5 months [95% CI 4·5-6·1] vs 4·3 months [4·1-5·3]; hazard ratio [HR] 0·72 [95% CI 0·55-0·94]; two-sided p=0·016). Significant progression-free survival benefit was sustained with sintilimab plus IBI305 plus chemotherapy compared with chemotherapy alone (median 7·2 months [95% CI 6·6-9·3]; HR: 0·51 [0·39-0·67]; two-sided p<0·0001). As of data cutoff (July 4, 2022), the median overall survival was 21·1 months (95% CI 17·5-23·9) for sintilimab plus IBI305 plus chemotherapy (HR 0·98 [0·72-1·34]) and 20·5 months (15·8-25·3) for sintilimab plus chemotherapy group (HR 0·97 [0·71-1·32]) versus 19·2 months (15·8-22·4) for chemotherapy alone; after adjusting for crossover, the HR for sintilimab plus IBI305 plus chemotherapy to chemotherapy alone ranged from 0·79 (0·57-1·09) to 0·84 (0·61-1·15) and the HR for sintilimab plus chemotherapy to chemotherapy alone ranged from 0·78 (0·57-1·08) to 0·84 (0·61-1·16). The safety results were generally consistent with those in the first interim analysis; in particular, treatment-related adverse events of grade 3 or worse occurred in 88 (56%) of 158 patients in the sintilimab plus IBI305 plus chemotherapy group, 64 (41%) of 156 patients in the sintilimab plus chemotherapy group, and 79 (49%) of 160 patients in the chemotherapy alone group. INTERPRETATION: This is the first prospective phase 3 trial to show the benefit of anti-PD-1 antibody plus chemotherapy in patients with EGFR-mutated NSCLC who progressed on treatment with tyrosine-kinase inhibitors. Compared with chemotherapy alone, sintilimab combined with pemetrexed and cisplatin showed significant and clinically meaningful improvement of progression-free survival with an optimal safety profile. Sintilimab plus IBI305 plus chemotherapy continued to show progression-free survival benefit compared with chemotherapy alone in this second interim analysis with an additional 8-month follow-up. FUNDING: National Natural Science Foundation of China, Shanghai Municipal Science & Technology Commission Research Project, and Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Prenatal Exposure to Air Pollution and Pre-Labor Rupture of Membranes in a Prospective Cohort Study: The Role of Maternal Hemoglobin and Iron Supplementation.

BACKGROUND: Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. OBJECTIVE: We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. METHOD: From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5), PM with aerodynamic diameter ≤10µm (PM10), sulfur dioxide (SO2), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. RESULTS: We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of PM2.5, PM10, SO2 and CO were the 21th to 24th weeks of pregnancy. Every 10-µg/m3 increase in PM2.5 and PM10, 5-µg/m3 increase in SO2, and 0.1-mg/m3 increase in CO was associated with low maternal hemoglobin levels [-0.94g/L (95% confidence interval (CI): -1.15, -0.73), -1.31g/L (95% CI: -1.55, -1.07), -2.96g/L (95% CI: -3.32, -2.61), and -1.11g/L (95% CI: -1.31, -0.92), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. CONCLUSIONS: Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.

Anemia in pregnancy and sleep of 6-month-old infants: A prospective cohort study.

Objective: Anemia has been reported to adversely influence sleep in infants. However, the association between anemia in pregnancy and infant sleep remains unclear. We aimed to examine the association between maternal anemia in pregnancy and sleep parameters of 6-month-old infants. Methods: We enrolled 2,410 mother-infant pairs between 2018 and 2021 in Hefei. Data on maternal hemoglobin concentration were collected at 24-28 gestational weeks from the electronic medical records of the hospitals. Nocturnal and daytime sleep duration, number of night awakenings, nocturnal wakefulness, and sleep latency of infants aged 6 months were measured using the Brief Infant Sleep Questionnaire with five items. A restricted cubic spline model was used to examine the relationship between maternal hemoglobin concentration and infant nocturnal sleep duration after adjusting for potential confounders. Results: In our study, 807 (33.5%) mothers had anemia during pregnancy. Compared to infants born to mothers without anemia, infants born to mothers with anemia in pregnancy had shorter nocturnal sleep duration [mean (SD), 560.29 (79.57) mins vs. 574.27 (75.36) mins] at the age of 6 months. Subgroup analysis showed consistent significant differences in nocturnal sleep duration between infant born to anemic and non-anemic mothers, except in case of stratification by preterm birth [mean difference (mins), 2.03 (95% CI, -20.01, -24.07)] and pre-pregnancy obesity [mean difference (mins), -0.85 (95% CI, -16.86, -15.16)]. A J-shaped nonlinear correlation curve was observed between maternal hemoglobin concentration and infant nocturnal sleep duration. Compared with mothers without daily iron supplementation, mothers who had daily iron supplementation had higher hemoglobin concentrations [mean (SD), 112.39 (11.33) g/L vs. 110.66 (10.65) g/L] at delivery and their infants had longer nocturnal sleep duration [mean (SD), 565.99 (82.46) mins vs. 553.66 (76.03) mins]. Conclusion: Anemia in pregnancy may have an adverse influence on the sleep of 6-mon-old infants, and the relationship between maternal hemoglobin concentration and nocturnal sleep duration is nonlinear.

Exploring the target and molecular mechanism of Astragalus membranaceus in the treatment of vascular cognitive impairment based on network pharmacology and molecular docking.

Astragalus membranaceus (AM) is a traditional Chinese herbal medicine extensively utilized in vascular cognitive impairment (VCI) treatment. However, due to the complex components of AM, its exact molecular mechanism remains unclear. Therefore, this study investigated the target and molecular mechanism of AM to treat VCI based on network pharmacology and molecular docking. Firstly, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, STITCH, and SwissTargetPrediction were utilized to gather the primary active ingredients of AM. The potential therapeutic targets of VCI were collected through GeneCards, OMIM, and DisGeNET databases. Secondly, the protein-protein interaction network was built using the STRING database. The enrichment analysis of gene ontology and the Kyoto Encyclopedia of Genes and Genome pathways was carried out in the R language. Finally, The network topology calculation of Cytoscape software was combined with module analysis to predict the binding properties of its active ingredients and targets. Twenty effective compounds and 733 targets were screened from AM, among which 158 targets were seen as possible targets of AM to treat VCI. MAPK3 and MMP9 were the critical targets of AM intervention in VCI. The crucial pathways include PI3K/Akt, MAPK, Rap1, and Ras signaling pathways. Besides, calycosin and quercetin might be the potential active compounds of AM for VCI treatment. AM intervenes in VCI through a multi-ingredient, multi-target, and multi-pathway coordination mechanism. These findings provide a foundation for a deeper understanding of the molecular mechanisms by which AM is effective in treating VCI.

A reference-grade genome assembly for Astragalus mongholicus and insights into the biosynthesis and high accumulation of triterpenoids and flavonoids in its roots.

Astragalus membranaceus var. mongholicus (AMM), a member of the Leguminosae, is one of the most important medicinal plants worldwide. The dried roots of AMM have a wide range of pharmacological effects and are a traditional Chinese medicine. Here, we report the first chromosome-level reference genome of AMM, comprising nine pseudochromosomes with a total size of 1.47 Gb and 27 868 protein-encoding genes. Comparative genomic analysis reveals that AMM has not experienced an independent whole-genome duplication (WGD) event after the WGD event shared by the Papilionoideae species. Analysis of long terminal repeat retrotransposons suggests a recent burst of these elements at approximately 0.13 million years ago, which may explain the large size of the AMM genome. Multiple gene families involved in the biosynthesis of triterpenoids and flavonoids were expanded, and our data indicate that tandem duplication has been the main driver for expansion of these families. Among the expanded families, the phenylalanine ammonia-lyase gene family was primarily expressed in the roots of AMM, suggesting their roles in the biosynthesis of phenylpropanoid compounds. The functional versatility of 2,3-oxidosqualene cyclase genes in cluster III may play a critical role in the diversification of triterpenoids in AMM. Our findings provide novel insights into triterpenoid and flavonoid biosynthesis and can facilitate future research on the genetics and medical applications of AMM.

Phosphorus fractions and iron oxides responsible for the variations in the Cd retention capacity in tropical soil aggregates under different cropping patterns.

The environmental behavior of Cd in soil has been widely studied because of its close relationship with food security and soil environmental pollution. In this study, the roles of P fractions and Fe oxides in the retention of Cd in typical tropical soil from five cropping patterns were investigated. Although there was no evident relationship between the Cd adsorption capacity and soil aggregate particle sizes, strong spatial associations of P, Fe, and Cd at the soil aggregates were observed via energy dispersive spectroscopy analysis. Among five cropping patterns, citrus plantations exhibited highest ratios (calculated by pixel area) of P overlapped with Cd (8.61%) and Fe overlapped with Cd (9.53%) in the microaggregates. Furthermore, the random forest model revealed that humic P and labile organic P greatly contributed to the sorptivity of Cd2+ by < 0.053 mm (13.3%) and 0.25-0.053 mm (13.4%) soil aggregates, respectively. Compared with the P fractions in different-sized soil aggregates, the contribution of Fe oxides to the sorption of Cd2+ by soil aggregates was more significant. Amorphous ferric oxide had the most significant contribution to the sorptivity of Cd2+ by < 0.053 mm (26.0%), 0.25-0.053 mm (23.0%), 2.0-0.25 mm (25.1%), and > 2.0 mm (33.9%) soil aggregates.

Dual-Responsive Curcumin-Loaded Nanoparticles for the Treatment of Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury (AKI) has been a global public health concern leading to high patient morbidity and mortality in the world. Nanotechnology-mediated antioxidative therapy has facilitated the treatment of AKI. Herein, a hierarchical curcumin-loaded nanodrug delivery system (NPS@Cur) was fabricated for antioxidant therapy to ameliorate AKI. The nanoplatform could respond to subacidic and reactive oxygen species (ROS) microenvironments. The subacidic microenvironment led to a smaller size (from 140.9 to 99.36 nm) and positive charge (from -4.9 to 12.6 mV), contributing to the high accumulation of nanoparticles. An excessive ROS microenvironment led to nanoparticle degradation and drug release. In vitro assays showed that NPS@Cur could scavenge excessive ROS and relieve oxidative stress in H2O2-induced HK-2 cells through reduced apoptosis, activated autophagy, and decreased endoplasmic reticulum stress. Results from cisplatin-induced AKI models revealed that NPS@Cur could effectively alleviate mitochondria injury and protect kidneys via antioxidative protection, activated autophagy, decreased endoplasmic reticulum stress, and reduced apoptosis. NPS@Cur showed excellent biocompatibility and low toxicity to primary tissues in mice. These results revealed that NPS@Cur may be a potential therapeutic strategy for efficiently treating cisplatin or other cause-induced AKI.

Benzophenone Rhamnosides and Chromones from Hypericum seniawinii Maxim.

Two new benzophenone glycosides, hypersens A and B, along with four known compounds, (S)-(+)-5,7-dihydroxy-2-(1-methylpropyl) chromone (3), 5,7-dihydroxy-2-isopropylchromone (4), urachromone B (5), and 3-8'' bisapigenin (6), were isolated from Hypericum seniawinii. The structures of new compounds (1 and 2) were elucidated according to comprehensive spectroscopic data analyses. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations. All isolated compounds were evaluated for their neuroprotective effect using corticosterone-induced PC12 cell injury. In addition, compounds 1-6 were evaluated for their anti-inflammatory activity in lipopolysaccharide-induced RAW 264.7 cells. Compound 6 was a biflavonoid and significantly inhibited the production of nitric oxide with an IC50 value of 11.48 ± 1.23 µM.

The association of knowledge, attitudes and behaviors related to salt with 24-h urinary sodium, potassium excretion and hypertensive status.

To understand the association between sodium and potassium consumption levels, hypertension and knowledge, attitudes and behaviors (KAB) toward salt and the commitment to effective sodium reduction and potassium supplementation to achieve the purpose of suppressing hypertension. A stratified multistage random sampling method was used to obtain a representative provincial sample of 7512 residents aged 18-69 years through a cross-sectional survey by the Salt Reduction and Hypertension Prevention Project (SRHPP) in Zhejiang Province of China in 2017-2018. A screening including demographic, anthropometric, salt-related KAB and physical measurements was implemented, and 24-h urine of approximately 1/5 of the participants was collected and tested. The mean age was 44.8 years, 50.1% were women, 44.0% lived in urban areas, and hypertension or prehypertension accounted for approximately 35.0%. The mean 24-h urinary sodium and potassium excretion were 3848.5 (1661.1) mg/d and 1491.1 (710.9) mg/d, respectively. KAB in urban areas was generally more favorable than in rural areas, women were better than men, and the optimal blood pressure group was better than the other two groups (P < 0.05). However, the awareness and correct use rate of salt-restricted spoons, low-sodium salt and nutrition labeling were lower. A multivariable linear regression model indicated that KAB had a smaller effect on sodium (two indicators effective for promoting sodium reduction) and a greater effect on potassium (six indicators effective for promoting potassium supplementation) and mainly focused on knowledge and behavior indicators. A multivariable logistic regression model indicated that mastering more knowledge and taking active measures could effectively reduce the transition to hypertension, even if the individual was already in prehypertension. There is much room for improvement of salt-related KAB in the Chinese population. A clear association indicates that KAB can help to reduce sodium and supplement potassium, especially potassium, and help to suppress the development of hypertension. The role of beliefs in KAB should be fully valued and improved, similar to knowledge and behaviors. This study provides important evidence and insight into China's efforts to meet the targets of salt reduction and hypertension prevention.

Hyjapones A-D, trimethylated acyphloroglucinol meroterpenoids from Hypericum japonicum thunb. With anti-inflammatory activity.

Four undescribed trimethylated acylphloroglucinol meroterpenoids, hyjapones A-D, along with seven known analogues, were isolated from Hypericum japonicum Thunb. Hyjapone A represents the first example of a double norflavesones-caryophyllene hybrid featuring a rare 6/6/9/4/6/6 hexacyclic frame. Hyjapone D was isolated as a natural product for the first time. Their structures and absolute configurations were established by comprehensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The anti-inflammatory activities of all compounds were evaluated using lipopolysaccharide-induced RAW264.7 cells. Hyperjapone A showed more pronounced anti-inflammatory effect through reducing the production of nitric oxide (IC50 value of 11.32 ± 2.10 µM) and proinflammatory cytokines. In addition, the mechanistic studies revealed hyperjapone A inhibited LPS-induced activation of nuclear factor-κB.