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Abstract Background Medication Treatment Satisfaction (M-TS) from the patients’ perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps. Methods Using PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM ). Results This review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test–retest reliability, results in 24 provided evidence of satisfactory test–retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability. Conclusions Most existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS.

In view of the electromagnetic interference existing in the well, it can greatly interfere with the voltage signal of the operational amplifier terminal collected by the dynamometer, and then affect the accuracy of the pressure value measured by the sensor. The design uses the domestic HC32L176 micro controller unit as the main control chip. Develop a dynamometer which uses the chip. Collect the voltage signal through the oscilloscope. Select the appropriate wavelet basis function, the number of decomposition layers, threshold rule and threshold function to decomposesignals containing noise. Filter out the high-frequency components of different layers,and then reconstruct the signal to obtain the denoising signal . Through Matlab simulation and practical test, the results show that the wavelet transform can achieve a good denoising of the collected voltage signal, and improve the reliability and stability of the bolt and cable dynamometer.

Abstract Cross‐domain object detection aims to generalize the distribution of features extracted by an object detector from an annotated domain to an unknown and unlabelled domain. Although one‐stage cross‐domain object detectors have significant advantages in deployment than two‐stage ones, they suffer from two problems. First, neglect of category features and inaccurate alignment between multiple category features would lead to decreased domain adaptation efficiency. Second, one‐stage detectors are more sensitive to imbalance of samples and negative samples severely affect the alignment process of domain adaptation. To overcome these two problems, an innovative category‐related attention domain adaptive method that refines discrimination for each category's feature has been proposed in this paper. In the proposed method, a group of domain discriminators is assigned to each category to refine the fine‐grained features between categories. The discriminators are trained via an adversarial discriminant framework to align the fine‐grained distributions cross different domains. A category attention alignment (CAA) module is proposed to navigate more attention to the foreground regions in instance‐level, which effectively alleviates the negative migration problem caused by the positive and negative sample imbalance of the one‐stage detector. Specifically, two sub‐modules in the CAA module are developed: a local CAA module and a global CAA module. These modules aim to optimize the domain offsets in both the local and global dimensions. In addition, a progressive global alignment module is designed to align image‐level features, offering prior knowledge of migration for the CAA module. The progressive global alignment module and CAA module collaboratively engage in benign competition with the backbone network across various levels. Extensive transferring experiments are conducted among cityscapes, foggy cityscapes, SIM10K, and KITTI. Experimental results show that the proposed method has much superior performance than other one‐stage cross‐domain detectors.

Abstract The polyionic liquid poly-PEGMA-r-METAC (PPM) with quaternary ammonium has been synthesized and evaluated as additive in aqueous lubricating fluids. The rheological behavior of aqueous lubricating fluids with PPM has been characterized to confirm PPM’s function as a viscosity modifier. The tribological behavior of aqueous lubricating fluids with PPM has been investigated on SRV-V and MTM testing machines. It was found that PPM has excellent viscosity-increasing, lubricating, and anti-wear properties as an additive for aqueous, which can be attributed to the ability of PPM to form the protective film and boundary tribofilm generated from complex tribochemical reaction on rubbing surface. The obtained PPM with dual functions of anti-corrosion additives and viscosity index improver can play an important role in diverse lubrication regimes.

Abstract Introduction Cervical cancer threatens women's health seriously. In recent years, the incidence of cervical cancer is on the rise, and the age of onset tends to be younger. Prevention, early diagnosis and specific treatment have become the main means to change the prognosis of cervical cancer patients. Metabolomics research can directly reflect the changes of biochemical processes and microenvironment in the body, which can provide a comprehensive understanding of the changes of metabolites in the process of disease occurrence and development, and provide new ways for the prevention and diagnosis of diseases. Objectives The aim of this study is to review the metabolic changes in cervical cancer and the application of metabolomics in the diagnosis and treatment. Methods PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2022. Results With the emergence of metabolomics, metabolic regulation and cancer research are further becoming a focus of attention. By directly reflecting the changes in the microenvironment of the body, metabolomics research can provide a comprehensive understanding of the patterns of metabolites in the occurrence and development of diseases, thus providing new ideas for disease prevention and diagnosis. Conclusion With the continuous, in-depth research on metabolomics research technology, it will bring more benefits in the screening, diagnosis and treatment of cervical cancer with its advantages of holistic and dynamic nature.

AbstractContext Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage.Objective To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms.Materials and methods TA concentrations of 1.563–25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats.Results TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression.Discussion and conclusions TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.

Insecticides are an indispensable and important tool for agricultural production. However, the inappropriate application of insecticides can cause damage to the food chain and ecosystem. Orius similis is an important predatory and natural enemy of Frankliniella occidentalis. Imidacloprid is widely used to control pests, but will inevitably exert adverse effects on O. similis. In order to determine the effect of different imidacloprid treatments on the ability of O. similis to prey on the 2nd-instar nymphs of F. occidentalis, we determined the toxicity and predation of imidacloprid on different stages of O. similis under contact and ingestion treatments. In addition, we used the Holling disc equation to evaluate the ability of O. similis to search and exhibit predatory activity following contact and ingestion treatments. Analysis showed that the highest LC10 and LC20 values for imidacloprid contact and ingestion toxicity treatment were 17.06 mg/L and 23.74 mg/L, respectively. Both imidacloprid treatments led toa reduction in the predatory of O. similis on prey. The functional responses of the 3rd to 5th instar nymphs, along with female and male O. similis adults to the 2nd-instar nymphs of F. occidentalis were consistent with the Holling type II response following contact and ingestion with imidacloprid. However, following imidacloprid treatment, the handing time (Th) of O. similis with single F. occidentalis was prolonged and the instantaneous attack rate (a) was reduced after imidacloprid treatment. The predatory capacity (a/Th) of female O. similis adults when treated with the LC10 concentration of imidacloprid by ingestion was 52.85; this was lower than that of the LC10 concentration of imidacloprid in the contact treatment (57.67). The extent of predation of O. similis on the 2nd-instar nymphs of F. occidentalis was positively correlated with prey density, although the search effect was negatively correlated with prey density. The most extensive search effect was exhibited by adult O. similis females. Simulations with the Hessell-Varley interference model showed that an increase in the number of O. similis would reduce search efficiency regardless of whether they were treated with imidacloprid or not. Thus, O. similis, especially female adults, exhibited strong potential for controlling the 2nd-instar nymphs of F. occidentalis. The toxicity of ingestion following treatment with the same concentration of imidacloprid in O. similis was greater than that of contact treatment. When using O. similis to control F. occidentalis in the field, we should increase the number of female adults released, and prolong the interval between imidacloprid treatment and O. similis exposure. This strategy will improve the control ability of O. similis, coordinate both chemical and biological control, reduce the impact of pesticides on the environment, and improve the efficiency of agricultural production.

Two new caryophyllene-type sesquiterpenes pestalotiopsins U and V (1 and 2) and three known compounds pestalotiopsin B (7), pestaloporinate B (8), and pestalotiopsin C (9) were isolated by the cultivation of the endophytic fungus Pestalotiopsis lespedezae on solid rice medium, while four additional new caryophyllene pestalotiopsins W–Z (3–6) were obtained when 3.5% NaI was added to the fungal culture medium. The structures of the new compounds were determined by HRESIMS and 1D/2D nuclear magnetic resonance data. Compounds 1–9 were tested for cytotoxicity against the mouse lymphoma cell line L5178Y, but only 6 displayed significant activity with an IC50 value of 2.4 μM.

Our prophase studies have manifested that the sweet triterpenoid glycoside from the leaves of Cyclocarya paliurus (CPST) effectively improved the disorders of glucolipid metabolism in vitro and in patients. The current purpose was to further detect its mechanisms involved. The results demonstrated that CPST could ameliorate high-fat diet (HFD)-induced insulin resistance (IR), which was linked to reducing HFD-induced mice's body weight, serum glucose (GLUO), triglyceride (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C), lowering the area under the oral glucose tolerance curve and insulin tolerance, elevating the percentage of brown adipose, high-density lipoprotein cholesterol (HDL-C), reducing fat droplets of adipocytes in interscapular brown adipose tissue (iBAT) and cross-sectional area of adipocytes. Further studies manifested that CPST obviously downregulated TLR4, MyD88, NLRP3, ASC, caspase-1, cleased-caspase-1, IL-18, IL-1β, TXNIP, and GSDMD protein expressions and p-NF-кB/NF-кB ratio in iBAT. These aforementioned findings demonstrated that CPST ameliorated HFD induced IR by regulating TLR4/NF-κB/NLRP3 signaling pathway, which in turn enhancing insulin sensitivity and glucose metabolism.

Summary: Aiming at the problem of insufficient security of image encryption technology, a secure image encryption algorithm using chaos-based block permutation and weighted bit planes chain diffusion is proposed, which is based on a variant structure of classical permutation-diffusion. During the permutation phase, the encryption operations of dividing an image into sub-block, block scrambling, block rotation and block inversion, negative-positive transformation, color component shuffling are performed sequentially with chaotic sequences of plaintext association. In the chain diffusion stage, different encryption strategies are adopted for the high and low 4-bit planes according to the weight of image information. Theoretical analyses and empirical results substantiate that the algorithm conforms to the cryptographic requirements of confusion, diffusion, and avalanche effects, while possessing excellent numerical statistical properties with a large cryptographic space. Therefore, the cryptanalysis-propelled security enhancement mechanism proposed in this paper effectively amplifies the aptitude of the algorithm to withstand cryptographic attacks.

The Ningbo International Conference Center Project incorporates elements of Chinese traditional culture into its architectural style, resulting in the world’s first cantilever bridge international conference center. During the construction process, it faced challenges such as complex engineering geological environments and diverse architectural styles. By harnessing building information modeling (BIM) technology, many challenges encompassing intricate environmental conditions, architectural structures, and construction complexities are effectively visualized in three dimensions, thereby offering viable solutions for engineering implementation. In the scheme design stage, BIM technology plays a pivotal role in bridging the gap between design and construction, optimizing engineering pile and wall material designs. During the deepening design stage, BIM aids in refining designs through intricate node optimization for the ultralong comb type inclined water panel curtain wall and glued wood column decoration, thereby enhancing construction efficiency. Additionally, BIM technology has also played an important role in the simulation and scheme analysis of the entire construction process of complex steel structures. Through the implementation of BIM technology, numerous challenges encountered during the construction phase of the Ningbo International Conference Center project have been effectively resolved, which serves as a valuable reference for employing BIM technology in large-scale international conference center projects.

Abstract Background Access to essential medicines is a vital component of universal health coverage. The low availability of essential medicines for children (EMC) has led the World Health Organization (WHO) to issue a number of resolutions calling on member states on its improvement. But its global progress has been unclear. We aimed to systematically evaluate the progress of availability of EMC over the past decade across economic regions and countries. Methods We searched eight databases from inception to December 2021 and reference lists to identify included studies. Two reviewers independently conducted literature screening, data extraction and quality evaluation. This study was registered with PROSPERO, CRD42022314003. Results Overall, 22 cross-sectional studies covering 17 countries, 4 income groups were included. Globally, the average availability rates of EMC were 39.0% (95%CI: 35.5-42.5%) in 2009–2015 and 43.1% (95%CI: 40.1-46.2%) in 2016–2020. Based on the World Bank classification of economic regions, income was not proportional to availability. Nationally, the availability rate of EMC was reasonable and high (> 50%) in only 4 countries, and low or very low for the rest 13 countries. The availability rates of EMC in primary healthcare centers had increased, while that for other levels of hospitals slightly declined. The availability of original medicines decreased while that of generic medicines was stable. All drug categories had not achieved the high availability rate. Conclusion The availability rate of EMC was low globally, with slight increase in the last decade. Continuous monitoring and timely reporting of the availability of EMC are also needed to facilitate targets setting and inform relevant policy making.

ObjectiveUsing Mesh Meta Analysis to evaluate the efficacy of Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene for treating Polycystic Ovary Syndrome (PCOS), in order to provide evidence-based medical evidence for whether to recommend Acupuncture & Moxibustion or Combine western medicine to treat PCOS.MethodsEight databases including The Cochrane Library, Pubmed, Embase, Web of Science, CNKI, Wanfang Date, VIP and CBM were searched by computer. The included research period is from the establishment of the database to May 2023, which concerned with randomized controlled trials involving Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene on ovulation induction and pregnancy outcome in patients with PCOS. The duration of the research paper is from 2016 to 2023.The inclusion criteria refer to the Rotterdam standards issued by the European Center for Human Reproduction and Embryology and the American Society of Reproductive Medicine in January 2003, or the Expert Consensus on the Diagnosis and Treatment of Polycystic Ovarian Syndrome by the Endocrinology Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association. Simultaneously exclude related diseases, repetitive literature, as well as literature with incomplete abstract information and no original data provided. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias included in the study, using Stata17.0 software for a mesh meta-analysis.ResultsSix randomized controlled trials were included, covering 1410 PCOS patients. Three interventions included Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene. Mesh Meta Analysis showed that in terms of improving ovulation rate, there was no statistical difference between Acupuncture & Moxibustion (A), Clomiphene (B), Clomiphene combined with Acupuncture & Moxibustion (C) (P>0.05).Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=0.15,95% CI (-0.51,0.80)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.60,95% CI (0.97,2.23)], Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.45,95% CI (0.91,1.99)]. In terms of pregnancy outcome, the difference between the three intervention methods was statistically significant (P

Abstract Background Gestational weight gain (GWG) criteria recommended by the Institute of Medicine may not be appropriate for Asians. Our aims are to investigate the association between GWG and adverse pregnancy outcomes, and to propose optimal total GWG and rates of GWG for Chinese women. Methods Prospective data of 51,125 mother-child pairs from 27 hospitals and community health care centers from Guizhou, Yunnan and Sichuan provinces in China between 2014 and 2018 were analyzed. Generalized Additive Models were performed to determine the associations of GWG with the risk of aggregated adverse outcomes (gestational diabetes mellitus, preeclampsia, cesarean delivery, stillbirth, preterm birth, macrosomia, large for gestational age, and small for gestational age). The range that did not exceed a 2.5% increase from the lowest risk of aggregated adverse outcomes was defined as the optimal GWG range. Results Among all participants, U-shaped prospective association was found between GWG and the risk of aggregated adverse pregnancy outcomes. The optimal GWG range of 8.2–13.0 kg was proposed for underweight, 7.3–12.5 kg for normal weight, and 2.0–9.4 kg for overweight/obese women. Meanwhile, a higher GWG rate in the first two trimesters than that in the last trimester was suggested, except for overweight/obese women. After stratified by maternal age, mothers ≥35 years were suggested to gain less weight compared to younger mothers. Conclusions To keep a balance between maternal health and neonatal growth, optimal GWG ranges based on Asia-specific BMI categories was suggested for Chinese women with different pre-gravid BMIs and maternal ages.

Abstract Our previous study showed that the flotillin level is decreased in the blood of patients with Alzheimer’s disease (AD) when compared to that of patients with non-AD and vascular dementia; however, the molecular mechanism remains to be determined. In this study, to elucidate whether Aβ accumulation in the brain has an effect on the blood flotillin level, we used our previously established blood–brain barrier (BBB) culture model using microvascular endothelial cells obtained from human induced pluripotent stem cells (iBMECs) and astrocytes prepared from rat cortex. In this BBB model with iBMECs plated on the upper compartment (blood side) and astrocytes plated on the lower compartment (brain side), the trans-endothelial electrical resistance values are high (over 1500 Ωm2) and stable during experiments. We found that the addition of Aβ42 (0.5 and 2 µM) to the brain side significantly reduced the level of flotillin secreted by iBMECs on the blood side. The level of basic fibroblast growth factor (FGF-2) in the brain side was significantly reduced by Aβ42 treatment, and was accompanied by a reduction in the level of phosphorylation of the fibroblast growth factor receptor in iBMECs. The brain-side Aβ42 treatment-induced reduction of flotillin secretion into the blood side was restored in a dose-dependent manner by the addition of FGF-2 into the brain side. These results indicated that Aβ accumulation in the brain side reduced FGF-2 release from astrocytes, which attenuated FGF-2-mediated iBMECs signaling via the FGF-2 receptor, and thereby reduced flotillin secretion from iBMECs on the blood side. Our findings revealed a novel signaling pathway crossing the BBB from the brain side to the blood side, which is different from the classical intramural periarterial drainage or lymphatic-system-to-blood pathway.

C76H65N13Cl2Ni3O9, monoclinic, P21/n, a = 15.937(4) Å, b = 16.805(4) Å, c = 27.463(7) Å, β = 94.613(3)°, V = 7332(3) Å3, Z = 4, Rgt (F) = 0.0490, wRref (F 2) = 0.1596, T = 298 K.

Presenilin, a transmembrane protein primarily known for its role in Alzheimer’s disease (AD) as part of the γ-secretase complex, has garnered increased attention due to its multifaceted functions in various cellular processes. Recent investigations have unveiled a plethora of functions beyond its amyloidogenic role. This review aims to provide a comprehensive overview of presenilin’s diverse roles in AD and other neurodegenerative disorders. It includes a summary of well-known substrates of presenilin, such as its involvement in amyloid precursor protein (APP) processing and Notch signaling, along with other functions. Additionally, it highlights newly discovered functions, such as trafficking function, regulation of ferritin expression, apolipoprotein E (ApoE) secretion, the interaction of ApoE and presenilin, and the Aβ42-to-Aβ40-converting activity of ACE. This updated perspective underscores the evolving landscape of presenilin research, emphasizing its broader impact beyond established pathways. The incorporation of these novel findings accentuates the dynamic nature of presenilin’s involvement in cellular processes, further advancing our comprehension of its multifaceted roles in neurodegenerative disorders. By synthesizing evidence from a range of studies, this review sheds light on the intricate web of presenilin functions and their implications in health and disease.

Abstract Background Diet quality in early childhood has a long-term impact on health outcomes. However, there are scarce dietary indexes for Chinese preschool children, and the existing indexes had limited validity and reliability. This study thus aimed to develop a dietary index for preschool children based on the Chinese Dietary Guideline and Chinese Dietary Reference Intakes and to assess their overall diet quality using the China Health and Nutrition Survey (CHNS). Methods The Chinese Preschooler Dietary Index (CPDI) included 11 components, covering 9 food group components and two nutrient components. The total scores of CPDI ranged from 0 to 90, with a higher score indicating greater diet quality. This study assessed the diet quality of 1742 preschoolers aged two to five years old from CHNS using the CPDI. Dietary intake data were obtained using three-day 24-h diet recalls, and sociodemographic information was also collected. Cochran-Mantel-Haensel (CMH) test was used to explore the association between demographic and CPDI total scores. The principal component analysis, correlation analysis and Cronbach’s alpha were used to evaluate the relative reliability and validity of the CPDI. Finally, a stepwise multiple regression analysis was performed to explore potential influencing factors of CPDI. Results Among the 1742 CHNS preschool children, more than 70% resided in rural areas and 41.2% of the sample were raised in a low-income family. The mean CPDI score of the preschoolers was 38.8 ± 12.9. Higher diet scores were correlated with higher energy and nutrient intake. Children with higher age (β = 0.93, SE = 0.26, P = 0.0003), raised in a home with higher household income (β = 3.11, SE = 0.27, P

Background: Essential medicine is a vital component to assure universal access to quality healthcare. However, the trend of affordability to essential medicines in China and its regional differences were not yet fully understood. This study aimed to systematically evaluate the price and affordability of essential medicines, their progress, and regional distribution in China in the last decades.Methods: We searched seven databases and three websites for potentially eligible studies from inception until March 2022. Studies on the price and affordability of essential medicines investigated in China were included. Median and interquartile range (IQR) was used to describe the price and affordability of essential medicines, and compared in three periods, before 2009, from 2009 to 2014, and from 2015 to 2019. Subgroup analysis was performed to examine the price and affordability by regions, health facilities, and ATC categories of medicines. The study was registered with PROSPERO (CRD42022310173).Results: A total of 65 studies including 11,639 health facilities investigated between 2006 and 2019 were included in this review. Median price ratios (MPR) and affordability of essential medicines were reported in 44 studies and 50 studies, respectively. The median MPRs of essential medicines in China was 1.59 (IQR: 5.39), with a tendency to rise first and then fall from 2006 to 2019. And the median affordability was equal to 0.88 (IQR: 2.58) days’ wage of the lowest paid unskilled government worker, but steadily rose from 2006 to 2019. Subgroup analysis showed that the affordability in the western region (1.40, IQR: 2.88), urban area (0.95, IQR: 2.80), private sector (0.90, IQR: 2.30), of originator brands (OB) (2.90, IQR: 6.68), and antineoplastic and immunomodulating agents (5.68, IQR: 56.47) were worse than their counterparts.Conclusion: The prices of essential medicine were higher than international level, the overall affordability of essential medicines in China is acceptable but poor in the western region, for OB drugs and anti-cancer medicines. Further national essential medicine policies are needed to reduce regional disparities and improve the affordability of expensive drugs.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails

Objective This study aimed to examine the clinical capability of township healthcare centres (THCs), the main primary care providers in rural China, as a basis for rural health service planning.Design Observational study of quantitative analysis using administrative data.Setting Three counties with low, middle and high social economic development level, respectively, in Sichuan province western China.Participants 9 THCs and 6 county hospitals (CHs) were purposively selected in the three counties. Summary of electronic medical records of 31 633 admissions from 1 January 2015 to 30 December 2015 of these selected health institutions was obtained from the Health Information Centre of Sichuan province.Main outcome measures Six indicators in scope of inpatient services related to diseases and surgeries in the THCs as proxy of clinical capability, were compared against national standard of capability building of THCs, among counties, and between THCs and CHs of each county.Results The clinical capability of THCs was suboptimal against the national standard, though that of the middle-developed county was better than that in the rich and the poor counties. THCs mainly provided services of infectious or inflammatory diseases, of respiratory and digestive systems, but lacked clinical services related to injuries, poisoning, pregnancy, childbirth and surgeries. A large proportion of the top 20 diseases of inpatients were potentially avoidable hospitalisations (PAHs) and were overlapped between THCs and CHs.Conclusions The clinical capability of THCs was generally suboptimal against national standard. It may be affected by the economics, population size, facilities, workforce and the share of services of THCs in local health systems. Identification of absent services and PAHs may help to identify development priorities of local THCs. Clarification of the roles of THCs and CHs in the tiered rural health system in China is warranted to develop a better integrated health system.

BackgroundEssential medicines are the backbone of healthcare and meet the priority healthcare needs of the population. However, approximately one-third of the global population does not have access to essential medicines. Although China formulated essential medicine policies in 2009, the progress of availability of essential medicines and regional variations remains unknown. Therefore, this study was conducted to evaluate the availability of essential medicines, their progress, and regional distribution in China in the last decade.MethodsWe searched eight databases from their inception to February 2022, relevant websites, and reference lists of included studies. Two reviewers selected studies, extracted data, and evaluated the risk of bias independently. Meta-analyses were performed to quantify the availability of essential medicines, their progress, and regional distribution.ResultsOverall 36 cross-sectional studies conducted from 2009 to 2019 were included, with regional data for 14 provinces. The availability of essential medicines in 2015–2019 [28.1%, 95% confidence interval (CI): 26.4–29.9%] was similar to that in 2009–2014 (29.4%, 95% CI: 27.5–31.3%); lower in the Western region (19.8%, 95% CI: 18.1–21.5%) than Eastern (33.8%, 95% CI: 31.6–36.1%) and Central region (34.5%, 95% CI: 30.6–38.5%); very low for 8 Anatomical Therapeutic Chemical (ATC) categories (57.1%), and low for 5 categories (35.7%) among all ATC groups.ConclusionThe availability of essential medicines in China is low compared with the World Health Organization goal, has not changed much in the last decade, is unequal across regions, and lacks data for half of provinces. For policy-making, the monitoring system of the availability of essential medicines is to be strengthened to enable long-term surveillance, especially in provinces where the data has been missing. Meanwhile, Joint efforts from all stakeholders are warranted to improve the availability of essential medicines in China toward the universal health coverage target.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=315267, identifier: PROSPERO CRD42022315267.

PurposeTo evaluate the feasibility of using a simplified non-coplanar volumetric modulated arc therapy (NC-VMAT) and investigate its dosimetric advantages compared with intensity modulated radiation therapy (IMRT) and coplanar volumetric modulated arc therapy (C-VMAT) for hippocampal-avoidance whole brain radiation therapy (HA-WBRT).MethodsTen patients with brain metastase (BM) were included for HA-WBRT. Three treatment plans were generated for each case using IMRT, C-VMAT, and NC-VMAT, respectively.ResultsThe dosimetric results of the three techniques complied roughly with the RTOG 0933 criteria. After dose normalization, the V30Gy of whole brain planned target volume (WB-PTV) in all the plans was controlled at 95%. Homogeneity index (HI) of WB-PTV was significantly reduced in NC-VMAT (0.249 ± 0.017) over IMRT (0.265 ± 0.020, p=0.005) and C-VMAT (0.261 ± 0.014, p=0.020). In terms of conformity index (CI), NC-VMAT could provide a value of 0.821 ± 0.010, which was significantly superior to IMRT (0.788 ± 0.019, p

Abstract Friction is an energy dissipation process. However, the electronic contribution to energy dissipation channels remains elusive during the sliding friction process. The friction and dissipation on atomically thin MoS2 with semiconductive characteristics are studied and tuned by the gate-modulated carrier concentration. The electronic contribution to energy dissipation of friction on atomically thin MoS2 was confirmed and regulated through tuning the strength of the electron-phonon coupling. The electron-phonon coupling can be strengthened and depressed to increase and decrease friction by the gate-modulation of the carrier concentration. The fitting of the friction on atomically thin MoS2 and carrier concentration is approximately linear which is in accordance with Langevin equation induced friction. Then the active, dynamical, and repeated tuning of friction on atomically thin MoS2 with semiconductive properties is achieved by the active modulation of carrier concentration with gate voltage. These observations help us to understand the electronic friction in essence, provide a utility approach to tune the friction intelligently on atomically thin two-dimensional materials with semiconductive properties and achieve superlubric properties for the application in various micro-and nanoelectromechanical systems.

Background: At present, only one systematic review has investigated the effect of levothyroxine (LT4) in the treatment of euthyroid pregnant women with thyroid autoimmunity, but some problems [such as merging different types of research for meta-analysis, lacking neonatal outcomes, and so on] exist in this study, satisfactory results can not be provided. So, this systematic review was performed to investigate the effect of LT4 in euthyroid pregnant women with thyroid autoimmunity, in the hope of providing more comprehensive evidence for clinical use.Methods: Medline (Ovid), Embase (Ovid), and Cochrane Central Register of Controlled Trials were electronically searched from database inception to March 2022. We included cohort studies and RCTs that evaluated the impact of LT4 therapy on pregnancy and neonatal outcomes in euthyroid pregnant women with thyroid autoimmunity. Meta-analyses of different types of studies were performed separately, and meta-analyses were further performed by only including researches with low and moderate risk of bias. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the quality of evidence, and used TSA to test the sufficiency of the evidence.Results: Finally, 2,901 euthyroid pregnant women with thyroid autoimmunity in six RCTs and five cohort studies were included. In all outcomes, no statistically significant differences were found between LT4 group and control group, including miscarriage [RR = 0.85, 95%CI (0.69,1.05), p = 0.14, I2 = 1%], preterm birth [RR = 0.80, 95%CI (0.59,1.08), p = 0.14, I2 = 0%], preeclampsia [RR = 0.68, 95%CI (0.12, 3.91), p = 0.66, I2 = 0%], placenta abruption [Peto’ OR = 0.14, 95%CI (0.00, 6.94), p = 0.32, I2 = 0%], birth weight [MD = -36.00, 95%CI (-170.41, 98.41), p = 0.60, I2 = 0%], gestational age at delivery [MD = -0.10, 95%CI (-0.61, 0.41), p = 0.70, I2 = 0%] and neonatal admission [RR = 1.33, 95%CI (0.21, 8.58), p = 0.76, I2 = 0%]. The results for all outcomes were insufficient and inconclusive as demonstrated by TSA. The GRADE assessments showed that the quality of evidence of 4 outcomes (miscarriage, preterm birth, birth weight and gestational age at delivery) were moderate, and 3 outcomes (preeclampsia, placenta abruption and neonatal admission) were low or very low.Conclusion: For pregnancy and neonatal outcomes in euthyroid pregnant women with thyroid autoimmunity, we did not find benefit of LT4 treatment in this study.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022346745, identifier CRD42022346745.

Dynamic motion primitive has been the most prevalent model-based imitation learning method in the last few decades. Gaussian mixed regression dynamic motion primitive, which draws upon the strengths of both the motion model and the probability model to cope with multiple demonstrations, is a very practical and conspicuous branch in the dynamic motion primitive family. As Gaussian mixed regression dynamic motion primitive only learns from expert demonstrations and requires full environmental information, it is incapable of handling tasks with unmodeled obstacles. Aiming at this problem, we proposed the positive and negative demonstrations-based dynamic motion primitive, for which the introduction of negative demonstrations can bring additional flexibility. Positive and negative demonstrations-based dynamic motion primitive extends Gaussian mixed regression dynamic motion primitive in three aspects. The first aspect is a new maximum log-likelihood function that balances the probabilities on positive and negative demonstrations. The second one is the positive and negative demonstrations-based expectation–maximum, which involves iteratively calculating the lower bound of a new Q-function. And the last is the application framework of data set aggregation for positive and negative demonstrations-based dynamic motion primitive to handle unmodeled obstacles. Experiments on several typical robot manipulating tasks, which include letter writing, obstacle avoidance, and grasping in a grid box, are conducted to validate the performance of positive and negative demonstrations-based dynamic motion primitive.

IntroductionAlzheimer’s disease (AD) is associated with amyloid β-protein 1-42 (Aβ42) accumulation in the brain. Aβ42 and Aβ40 are the major two species generated from amyloid precursor protein. We found that angiotensin-converting enzyme (ACE) converts neurotoxic Aβ42 to neuroprotective Aβ40 in an ACE domain– and glycosylation-dependent manner. Presenilin 1 (PS1) mutations account for most of cases of familial AD and lead to an increased Aβ42/40 ratio. However, the mechanism by which PSEN1 mutations induce a higher Aβ42/40 ratio is unclear.MethodsWe over expressed human ACE in mouse wild-type and PS1-deficient fibroblasts. The purified ACE protein was used to analysis the Aβ42-to-Aβ40- and angiotensin-converting activities. The distribution of ACE was determined by Immunofluorescence staining.ResultWe found that ACE purified from PS1-deficient fibroblasts exhibited altered glycosylation and significantly reduced Aβ42-to-Aβ40- and angiotensin-converting activities compared with ACE from wild-type fibroblasts. Overexpression of wild-type PS1 in PS1-deficient fibroblasts restored the Aβ42-to-Aβ40- and angiotensin-converting activities of ACE. Interestingly, PS1 mutants completely restored the angiotensin-converting activity in PS1-deficient fibroblasts, but some PS1 mutants did not restore the Aβ42-to-Aβ40-converting activity. We also found that the glycosylation of ACE in adult mouse brain differed from that of embryonic brain and that the Aβ42-to-Aβ40-converting activity in adult mouse brain was lower than that in embryonic brain.ConclusionPS1 deficiency altered ACE glycosylation and impaired its Aβ42-to-Aβ40- and angiotensin-converting activities. Our findings suggest that PS1 deficiency and PSEN1 mutations increase the Aβ42/40 ratio by reducing the Aβ42-to-Aβ40-converting activity of ACE.

Cutaneous pigmentation was recently shown to be an event regulated by clock proteins. Cryptochrome (CRY) is a key protein composing the feedback loop of circadian clock, however, the function of CRY in melanocytes remains unclear. Here, we found that KL001, a synthetic small molecule modulator of CRY1, inhibited melanin synthesis, as well as reduced melanocyte dendrite elongation and melanosome transport. In addition, the dominant role of CRY1 in KL001-induced anti-melanogenesis was revealed by small interfering RNA transfection. Cellular tyrosinase activity and expression level of melanogenic proteins, including tyrosinase, TRP-1, TRP-2, and transport proteins like Rab27a, Cdc42 and Myosin Va induced by α-MSH were remarkably reversed after KL001 treatment. Mechanistically, CRY1 activation inhibited melanogenesis through CREB-dependent downregulation of MITF and CREB phosphorylation was mediated by classical cAMP/PKA pathway. In addition, the other CRY1 activator, KL044 also suppressed cAMP/PKA/CREB pathway and inhibited melanogenesis. Finally, anti-melanogenic efficacy of KL001 was confirmed by determination of melanin contents in UVB-tanning model of brown guinea pigs, which indicated that targeting CRY1 activity, via topical application of small molecule activator, can be utilized therapeutically to manage human pigmentary disorders.

Background: The role of antihypertensive drugs in inducing hyperuricaemia and gout has been a long-term concern in clinical practice. However, clinical studies regarding this issue are limited in number and have yielded inconsistent results. We comprehensively evaluated the association between various antihypertensive drugs and the occurrences of hyperuricaemia, gout and related adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS), aiming to guide the selection of antihypertensive drugs with a goal of minimizing the risk of hyperuricaemia, gout and related AEs.Methods: We used OpenVigil 2.1 to query the FAERS database. Hyperuricaemia, gout and related AEs were defined by 5 Preferred Terms: hyperuricaemia, gout, gouty arthritis, gouty tophus and urate nephropathy. Disproportionality analysis was performed, and a positive signal indicated an association between AEs and antihypertensive drugs.Results: The numbers of antihypertensive drugs with positive signals for hyperuricaemia, gout, gouty arthritis, gouty tophus and urate nephropathy were 46, 66, 27, 8 and 6, respectively. These drugs included diuretics, antihypertensive drugs with central action, α blockers, β blockers, α and β blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, renin inhibitors, vasodilators, and compound preparations. Furthermore, 42 antihypertensive drugs had positive signal for more than one AEs.Conclusion: Our study suggests that some potassium-sparing diuretics, calcium channel blockers and losartan may be associated with increased risk of hyperuricaemia, gout or related AEs, which is inconsistent with most previous studies. Moreover, Our study also suggests that some antihypertensive drugs with central action, α and β blockers, renin inhibitors and vasodilators may be associated with increased risk of hyperuricaemia, gout or related AEs, which has not been reported in previous studies. These findings complement real-world evidence on the potential risks of hyperuricaemia, gout and related AEs associated with antihypertensive drugs.

ObjectiveTo evaluate the incidence and trend of catastrophic health expenditures (CHE) in China over the past 20 years and explore the socioeconomic factors affecting China's CHE rate.MethodsThe systematic review was conducted according to the Cochrane Handbook and reported according to PRISMA. We searched English and Chinese literature databases, including PubMed, EMbase, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang, China Science and Technology Journal Database (CQVIP), and CBM (Sino Med), for empirical studies on the CHE rate in China and its associated socioeconomic factors from January 2000 to June 2020. Two reviewers conducted the study selection, data extraction, and quality appraisal. The secular trend of the CHE rate was examined, and factors associated with CHE were explored using subgroup analysis and meta-regression.ResultsA total of 118 eligible studies with 1,771,726 participants were included. From 2000 to 2020, the overall CHE rate was 25.2% (95% CI: 23.4%−26.9%) in China. The CHE rate continued to rise from 13.0% in 2000 to 32.2% in 2020 in the general population. The CHE rate was higher in urban areas than in rural areas, higher in the western than the northeast, eastern, and central region, in the elderly than non-elderly, in low-income groups than non-low-income groups, in people with cancer, chronic infectious disease, and cardio-cerebrovascular diseases (CCVD) than those with non-chronic disease group, and in people with NCMS than those with URBMI and UEBMI. Multiple meta-regression analyses found that low-income, cancer, CCVD, unspecified medical insurance type, definition 1 and definition 2 were correlated with the CHE rate, while other factors were all non-significantly correlated.ConclusionIn the past two decades, the CHE rate in China has been rising. The continuous rise of health expenditures may be an important reason for the increasing CHE rate. Age, income level, and health status affect the CHE rate. Therefore, it is necessary to find ways to meet the medical needs of residents and, at the same time, control the unreasonable rapid increase in health expenditures in China.

Primary intracranial mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of brain tumor, with only a few reported cases worldwide that mostly have only one lesion with conventional magnetic resonance imaging (MRI) findings. Here, we present a special case of intracranial MALT lymphoma with two mass lesions radiographically consistent with meningiomas on MRI before the operation. A 66-year-old woman was admitted to the hospital with intermittent right facial pain for 1 year, aggravated for the last month. Brain MRI showed two extracerebral solid masses with similar MR signal intensity. One mass was crescent-shaped beneath the skull, and the other was in the cavernous sinus area. Lesions showed isointensity on T1WI and T2WI and an intense homogeneous enhancement after contrast agent injection. Both lesions showed hyperintensity in amide proton transfer–weighted images. The two masses were all surgically resected. The postoperative pathology indicated extranodal marginal zone B-cell lymphoma of MALT. To improve awareness of intracranial MALT lymphoma in the differential diagnosis of extra-axial lesions among clinicians, we present this report and briefly summarize previously reported cases to describe the clinical, pathological, radiological, and treatment features.

Abstract Background Hip fracture is frequent in older people and represents a major public health issue worldwide. The increasing incidence of hip fracture and the associated hospitalization costs place a significant economic burden on older patients and their families. On January 1, 2018, the Chinese diagnosis-related group (C-DRG) payment system, which aims to reduce financial barriers, was implemented in Sanming City, southern China. This study aimed to evaluate the associations of C-DRG system with inpatient expenditures for older people with hip fracture. Methods An uncontrolled before-and-after study employed data of all the patients with hip fracture aged 60 years or older from all the public hospitals enrolled in the Sanming Basic Health Insurance Scheme from January 1, 2016 to December 31, 2018. The ‘pre C-DRG sample’ included patients from January 1, 2016 to December 31, 2017. The ‘post C-DRG sample’ included patients from January 1, 2018 to December 31, 2018. A propensity score matching analysis was used to adjust the difference in baseline characteristic parameters between the pre and post samples. Data were analyzed using generalized linear models adjusted for the demographic, clinical, and institutional factors. Robust tests were performed by accounting for time trend, the fixed effects of the year and hospitals, and clustering effect within hospitals. Results After propensity score matching, we obtained two homogeneous groups of 1123 patients each, and the characteristic variables of the two matched groups were similar. We found that C-DRG reform was associated with a 19.51% decrease in out-of-pocket (OOP) payments (p

Immunotherapy has shown great promise in the field of oncology, and recent clinical trials have illustrated that immune checkpoint blockade (ICB) is safe and effective at treating a range of tumor types. Cervical cancer (CC) is the fourth most common malignancy in women. However, first-line treatments for locally advanced cervical cancer (LACC) and recurrent/metastatic (R/M) CC have limited efficacy. Thus, it is necessary to explore new treatment approaches. The National Comprehensive Cancer Network (NCCN) currently recommends pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, as a first line therapy for individuals with R/M CC. This study reviews the progress of ICB therapy for LACC and R/M CC and describes the current status of the combination of ICB therapy and other therapeutic modalities, including radiotherapy, chemotherapy, targeted therapy, and other immunotherapies. The focus is placed on studies published since 2018 with the aim of highlighting novel CC-specific immunotherapeutic approaches and treatment targets.

During the COVID-19 pandemic, little is known about parental hesitancy to receive the COVID-19 vaccine for preschool children who are the potential vaccinated population in the future. The purpose of this mixed-method study was to explore the factors influencing Chinese parents’ decision to vaccinate their children aged 3–6 years old against COVID-19. In July 2021, we conducted semi-structured interviews (n = 19) and a cross-sectional survey (n = 2605) with parents of kindergarten children in an urban-rural combination pilot area in China. According to the qualitative study, most parents were hesitant to vaccinate their children with the COVID-19 vaccine. In the quantitative study, we found that three-fifths of 2605 participants were unwilling to vaccinate their children against COVID-19. Furthermore, the main predictors of parents’ intention to vaccinate their children were fathers, lower level of education, and positive attitudes toward vaccination. Based on our findings, targeted health education techniques may be able to boost childhood COVID-19 immunization rates.

BackgroundCompared with high-income countries, the survival rate of childhood cancer is lower in low- and middle-income countries. Access to essential anticancer medicines is an indispensable component of pediatric cancer treatment, which is still a big challenge in low- and middle-income countries.ObjectiveTo assess the accessibility of essential anticancer medicines for children in public hospitals in the Sichuan Province of China.MethodsBased on the data of the Sichuan Province Drug Use Monitoring Platform in 2020, a retrospective study was conducted to investigate the original brands and generics of 34 anticancer and three supportive essential medicines for children (a total of 97 specific strengths) in Sichuan Province. The availability, price, and affordability of surveyed medicines were evaluated in all 152 tertiary public hospitals (120 general hospitals, 31 children's hospitals, and one cancer hospital) that could diagnose and treat cancer for children.ResultsThe average availability of generics and original brands was 18.5% and 2.6%, respectively. In regions with different gross domestic product (GDP) per capita levels, the average availability was similar, but the city with lower GDP per capita levels had fewer tertiary public hospitals. The prices of most original brands were higher than the lowest-priced generics, and the median price ratios of 31 lowest-priced generics and 16 original brands were 0.744 (P25~P75, 0.446~2.791) and 2.908 (1.719~6.465). After paying medical insurance for medicines, the affordability of essential anticancer medicines was improved. The monthly medicine cost did not exceed 10% of the monthly household income for 78.9% (30/38) of the lowest-priced generics and 50.0% (8/16) of the original brands.ConclusionThe availability of lowest-priced generics was higher than original brands in public hospitals, but the availability of both was low, which was similar to previous studies in low- and middle-income countries. About half of the lowest-priced generics and 87.5% of the original brands cost more than 1.5 times the International Reference Price. Although the National Basic Medical Insurance greatly improved the affordability of essential anticancer medicines for children, higher subsidies for essential medicines for cancer treatment to limit catastrophic health expenditures are still recommended.

Access to essential medicines for children is a big challenge, particularly in low-income and middle-income countries. In China, the average availability of essential medicines for children is 1.6%–46.5%. The availability of generics was generally higher than original brands in public hospitals and the prices of generics were relatively lower and more reasonable (generics: availability, 27.3%–46.5%, prices, 0.52–4.28 times the international reference prices; original brands: 1.6%–33.0%, 2.59–11.38 times the international reference prices). In terms of affordability of medicines for children, generics were more affordable than original brands and tablets/capsules were more affordable than injections. Most commonly used anti-infective medicines (such as amoxicillin capsule, azithromycin tablet, cefuroxime tablet) and antipyretics (such as ibuprofen suspension) were relatively affordable. Six commonly used medicines in paediatrics, including amoxicillin/clavulanic acid, beclomethasone, cefazolin, ceftazidime, ceftriaxone, cyclosporine were unaffordable. Since August 2011, China has successively issued several policies to ensure the accessibility of medicines for children, covering research and development, production, procurement and prices of medicines. The accessibility of medicines for children has been partially improved, but still needs continuous improvement.

Abstract The role of diet in depression is becoming increasingly acknowledged. This umbrella review aimed to summarize comprehensively the current evidence reporting the effects of dietary factors on the prevention and treatment of depression. PubMed, Embase, and the Cochrane Library were searched up to June 2021 to identify relevant meta-analyses of prospective studies. Twenty-eight meta-analyses, with 40 summary estimates on dietary patterns (n = 8), food and beverages (n = 19), and nutrients (n = 13) were eligible. The methodological quality of most meta-analyses was low (50.0%) or very low (25.0%). Quality of evidence was moderate for inverse associations for depression incidence with healthy diet [risk ratio (RR): 0.74, 95% confidential interval (CI), 0.48–0.99, I 2 = 89.8%], fish (RR: 0.88, 95% CI, 0.79–0.97, I 2 = 0.0%), coffee (RR: 0.89, 95% CI, 0.84–0.94, I 2 = 32.9%), dietary zinc (RR: 0.66, 95% CI 0.50–0.82, I 2 = 13.9%), light to moderate alcohol (

Abstract Background The biofilm state of pathogens facilitates antimicrobial resistance which makes difficult-to-treat infections. In this regard, it has been found that the compounds screened from plant extracts represent one category of the most promising antibiofilm agents. However, the antibiofilm activities and the active ingredients of plant extracts remain largely unexplored. In this background, the study is (1) to screen out the plant extracts with antibiofilm ability against Pseudomonas aeruginosa, and (2) to identify the active ingredients in the plant extracts and elucidate the underlying mechanism of the antibiofilm activities. Methods Micro-broth dilution method, in vitro biofilm model, LC–MS/MS analysis and P. aeruginosa-mouse infection model were adopted to assess the antibiofilm activity. GC–MS analysis was performed to detect the active ingredients in plasma. RNA-Seq, GO analysis, KEGG analysis and RT-qPCR were adopted to elucidate the underlying mechanism of antibiofilm activities against P. aeruginosa. Results Lonicerae Japonicae Flos (LJF) among 13 plants could exert significant inhibitory effects on bacterial biofilm formation, mobility and toxin release in vitro, and it could exert antibiofilm effect in vivo too. Moreover, quinic acid, as one metabolite of chlorogenic acid, was found as an active ingredient in LJF against the biofilm of P. aeruginosa. The active ingredient significantly inhibited EPS secretion in biofilm formation and maturity and could achieve synergistic antibiofilm effect with levofloxacin. It reduced the biofilm formation by regulating core targets in quorum sensing system. In GO process, it was found that the core targets were significantly enriched in multiple biological processes involving locomotion, chemotaxis and motility mediated by flagellum/cilium, which was related to KEGG pathways such as bacterial chemotaxis, oxidative phosphorylation, ribosome, biofilm formation, cyanoamino acid metabolism and quorum sensing. Finally, the binding of quinic acid with core targets rhlA, rhlR and rhlB were validated by molecular docking and RT-qPCR. Conclusions In summary, the study verified the in vitro and in vivo antibiofilm effects of LJF against P. aeruginosa and elucidated the active ingredients in LJF and its conceivable pharmacological mechanism, indicating that quinic acid could have the potential of an antibiofilm agent against P. aeruginosa and related infections. Graphic abstract

BackgroundSeveral systematic reviews and meta-analyses have investigated the effect of levothyroxine (LT4) therapy in pregnant women with subclinical hypothyroidism (SCH). However, all these studies have clinical or methodological problems (such as adopting the old 2011 American Thyroid Association [ATA] diagnostic criteria, directly combining randomized controlled trials [RCTs] and cohort studies for meta-analysis, and so on), and cannot provide accurate and satisfactory results. Thus, we performed this updated systematic review, meta-analysis and trial sequential analysis (TSA) to assess the effect of LT4 therapy in pregnant women with SCH, with the goal of providing more accurate and reliable evidence for clinical practice.MethodsWe searched nine databases from inception to February 2022. The search strategy targeted the RCTs and cohort studies on pregnancy, neonatal and childhood outcomes following LT4 treatment in pregnant women with SCH based on the new 2017 ATA diagnostic criteria. We performed meta-analyses of RCTs and cohort studies separately, and further performed meta-analyses by excluding studies with high risk of bias. TSA was performed to test whether the current evidence was sufficient, and the quality of evidence was evaluated using the GRADE method.ResultsA total of 9 RCTs and 13 cohort studies comprising 11273 pregnant women with SCH were included. There were no statistically significant differences between LT4 group and control group in all primary and secondary outcomes, such as preterm delivery (RR=0.46, 95%CI: 0.19-1.09, P=0.08, I2 = 65%), miscarriage (RR=0.36, 95%CI: 0.13-1.03, P=0.06, I2 = 38%), gestational hypertension (RR=0.91, 95%CI: 0.58-1.43, P=0.69, I2 = 0%), preeclampsia (RR=1.10, 95%CI: 0.61-1.97, P=0.76, I2 = 0%), gestational diabetes (RR=0.80, 95%CI: 0.51-1.25, P=0.32, I2 = 34%), and so on. TSA showed that the results for all outcomes were insufficient and inconclusive. According to GRADE, the evidences for four outcomes (miscarriage, gestational hypertension, gestational diabetes, and small for gestational age) were rated as moderate quality, while the evidences for the other outcomes were rated as low or very low quality.ConclusionUnlike previous systematic reviews and meta-analyses, our study found no evidence of benefit of LT4 therapy on pregnancy, neonatal and childhood outcomes in pregnant women with SCH.Systematic Review RegistrationPROSPERO, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022321937, identifier CRD42022321937.

Abstract Background In order to solve the problem of “expensive medical treatment and difficult medical treatment” for patients and improve the equity of medical services, China started the health-care reform in 2009, and proposed ambitious goals of providing fair and high-quality basic medical and health services to all citizens and reducing economic burden of diseases. This study was to systematically explore the association between population economic status and incidence of catastrophic health expenditures (CHE) in mainland China in the last decade since 2009 health reform. Methods This systematic review was reported according to the standard of preferred reporting items for systematic reviews and meta-analyses (PRISMA). We systematically searched Chinese Electronic literature Database of China Journal Full Text Database, Chinese Biomedical Journal Database, Wan fang Data Resource System, VIP Database, and English literature databases of PubMed, SCI, EMbase and Cochrane Library from January 2000 to June 2020, and references of included studies. Two reviewers independently selected all reports from 2000 to 2020 for empirical studies of CHE in mainland China, extracted data and evaluated the quality of the study. We conducted meta-analysis of the incidence of CHE and subgroup analysis according to the time of the study and the economic characteristics of residents. Results Four thousand eight hundred seventy-four records were retrieved and eventually 47 studies with 151,911 participants were included. The quality scores of most of studies were beyond 4 points (91.49%). The pooled incidence of CHE of Chinese residents in the last two decades was 23.3% (95% CI: 21.1 to 25.6%). The CHE incidence increased from 2000 to 2017, then decreased over time from 2017 to 2020. From 2000 to 2020, the CHE incidence in rural areas was 25.0% (95% CI: 20.9 to 29.1%) compared to urban 20.9% (95% CI: 18.3 to 23.4%); the CHE incidence in eastern, central and western China was 25.0% (95% CI: 19.2 to 30.8%), 25.4% (95% CI: 18.4 to 32.3%), and 23.1% (95% CI: 17.9 to 28.2%), respectively; the CHE incidence was 30.9% (95% CI: 22.4 to 39.5%), 20.3% (95% CI: 17.0 to 23.6%), 19.9% (95% CI: 15.6 to 24.1%), and 23.7% (95% CI: 18.0 to 29.3%) in poverty group, low-income group, middle-income group, and high-income group, respectively. Conclusions In the past two decade, the incidence of CHE in rural areas is higher than that of urban residents; higher in central areas than in eastern, western and other regions; in poverty households than in low-income, middle-income and high-income regions. Further measures should be taken to reduce the incidence of CHE in susceptible people.

Abstract Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.

Alzheimer’s disease (AD) is a genetic and sporadic neurodegenerative disease characterized by extracellular amyloid-β-protein (Aβ) aggregates as amyloid plaques and neuronal loss in the brain parenchyma of patients. Familial AD (FAD) is found to be genetically linked to missense mutations either in presenilin (PS) or amyloid precursor protein (APP). Most of PS mutations increase Aβ42/Aβ40 ratio, which is thought to result in early amyloid deposition in brain. However, PS deficiency in the fore brain of adult mouse leads to neuronal loss in an Aβ independent manner and the underlying mechanism is largely unknown. In this study, we found that reactive oxygen species (ROS) are increased in PS deficient fibroblasts and that H2O2 and ferrous sulfate treatment produced more ROS in PS deficient fibroblasts than in wild-type fibroblasts. PS deficient fibroblasts showed significantly decreased cellular ferritin levels compared with wild-type fibroblasts, suggesting reduced iron sequestrating capability in PS deficient cells. Blockade of γ-secretase activity by a γ-secretase inhibitor, DAPT, decreased ferritin levels, indicating that γ-secretase activity is important for maintaining its levels. Moreover, overexpression PS1 mutants in wild-type fibroblasts decreased ferritin light chain levels and enhanced intracellular ROS levels. Our results suggest that dysfunction of PS may reduce intracellular ferritin levels and is involved in AD pathogenesis through increasing susceptibility to oxidative damage.

Introduction: It is not clear whether there are differences in the risk factors for nonsuicidal self-injury (NSSI) between children and early adolescents. Clarifying this question is crucial for identifying actionable prevention strategies for NSSI in these two age groups. Method: The study, comprising 8611 children and early adolescents (4409 (51.2%) children, 4202 (48.8%) early adolescents), was based on the baseline data of the Chengdu Positive Child Development (CPCD) in China. NSSI behaviours, emotional and behavioural problems and family environment were assessed and obtained via self-reports and parent reports. Results: Overall, 2520 (29.26%) participants reported having ever engaged in NSSI. There was a higher lifetime NSSI rate in males than in females during childhood, contrasting with higher NSSI rates in females than in males during early adolescence. Furthermore, NSSI shared similar risk factors, including major family conflict and poor relationships with caregivers, in both age groups. Specifically, in children, the risk of NSSI increased along with thought and attention problems (OR, 95% CI: 1.194, 1.106–1.288 and 1.114, 1.028–1.207, respectively), whereas in early adolescents, it increased with anxiety and depressive problems (OR, 95% CI: 1.259, 1.116–1.422). Conclusions: The findings suggested the need for difference in preventive strategies for NSSI in the two age groups. It may be more efficacious to screen for NSSI in children with thought and attention problems and in early adolescents with anxiety and depressive problems.

Abstract Smoking has a substantial impact on deaths from non-communicable chronic diseases (NCDs). Quantitatively measuring the impact of tobacco control on population health is of great theoretical and practical importance, for governments to make health policy decisions. Focusing on premature deaths, we predicted the deaths by 2030 from major NCDs caused by smoking among people aged 30–69 years in Sichuan Province, Southwest China. We extracted data for 1990–2015 from the Global Burden of Disease Study 2015 and calculated the population attributable fraction, to estimate the proportion of deaths caused by smoking. Four different tobacco control standards were used to estimate 2030 projections for the prevalence of smoking and premature mortality. If smoking prevalence were reduced by 30% from 2015 levels, premature mortality could be expected to decline by 24.4% in 2030, achieving 81.3% of the World Health Organization target for reducing premature mortality by 30%. Compared with the continuation of historical trends, the strongest tobacco control policy scenario would reduce premature mortality by 6.6%, prevent 23,600 deaths, reduce mortality by 7.8%, and increase life expectancy at birth by 0.3 years. Smoking bans represent an important action toward achieving national health goals.

Konjac glucomannan (KGM) can be degraded by colon-specific enzymes in the colonic environment, making it one of the materials for treating colonic diseases, which has attracted more and more attention. However, during drug administration, especially in the gastric environment and due to its easy swelling, the structure of KGM is usually destroyed and the drug is released, thereby reducing the bioavailability of the drug. To solve this problem, the easy swelling and drug release properties of KGM hydrogels are avoided by creating interpenetrating polymer network hydrogels. In this study, N-isopropylacrylamide (NIPAM) is first formed into a hydrogel framework under the action of a cross-linking agent to stabilize the gel shape before the gel is heated under alkaline conditions to make KGM molecules wrap around the NIPAM framework. The structure of the IPN(KGM/NIPAM) gel was confirmed using Fourier transform infrared spectroscopy (FT-IR) and x-ray diffractometer (XRD). In the stomach and small intestine, it was found that the release rate and swelling rate of the gel were 30% and 100%, which were lower than 60% and 180% of KGM gel. The experimental results showed that this double network hydrogel has a good colon-directed release profile and fine drug carrier ability. This provides a new idea for the development of konjac glucomannan colon-targeting hydrogel.

(E)-7-Phenyl-2-hepten-4,6-diyn-1-ol (1) and (Z)-7-Phenyl-2-hepten-4,6-diyn-1-ol (2) are isomeric natural polyacetylenes isolated from the Chinese medicinal plant Bidens pilosa L. This study first revealed the excellent anti-metastasis potential of these two polyacetylenes on human gastric cancer HGC-27 cells and the distinctive molecular mechanisms underlying their activities. Polyacetylenes 1 and 2 significantly inhibited the migration, invasion, and adhesion of HGC-27 cells at their non-toxic concentrations in a dose-dependent manner. The results of a further mechanism investigation showed that polyacetylene 1 inhibited the expressions of Vimentin, Snail, β-catenin, GSK3β, MST1, YAP, YAP/TAZ, and their phosphorylation, and upregulated the expression of E-cadherin and p-LATS1. In addition, the expressions of various downstream metastasis-related proteins, such as MMP2/7/9/14, c-Myc, ICAM-1, VCAM-1, MAPK, p-MAPK, Sox2, Cox2, and Cyr61, were also suppressed in a dose-dependent manner. These findings suggested that polyacetylene 1 exhibited its anti-metastasis activities on HGC-27 cells through the reversal of the EMT process and the suppression of the Wnt/β-catenin and Hippo/YAP signaling pathways.

Abstract Background Radiotherapy is regarded as a milestone for the cure of cervical cancer. However, clinical outcome heavily be hindered by radioresistance. So, exploring the underlying mechanism of radioresistance, and find potential target, well deserve fully emphasis. Methods In this study, we developed two novel radiation resistance cervical cancer cell lines, which could mimic clinical radioresistance. In order to find new potential targets, RNA-Seq, database analysis, streptavidin-agarose and LC/MS were used. Pull-down, luciferase and rescue assays were conducted to explore the regulatory mechanisms. To further evaluate the correlation between therapeutic responses and HMGB3/hTERT expression, 172 cervical cancer patients were recruited. Results Knockdown of HMGB3 significantly inhibit the DNA damage repair and induced more γH2AX foci, leading to enhanced chemo- and radio-sensitivity in vitro and in vivo, whereas HMGB3 overexpression has the opposite effects. HMGB3 promotes cell growth and radioresistance by transcriptionally up-regulating hTERT via the specifical binding of HMGB3 at the hTERT promoter region from − 902 to − 321. HMGB3 knockdown-mediated radiosensitization could be reversed by the overexpressed hTERT in both cervical cancer cell lines and xenograft tumor mouse model. Furthermore, clinical data from 172 cervical cancer patients proved that there was a positive correlation between HMGB3 and hTERT expression, and high expression of HMGB3/hTERT predicted poor response to radiotherapy, worse TNM stages and shorter survival time. Conclusion Here, we have identified HMGB3/hTERT signaling axis as a new target for cervical cancer radioresistance. Our results provide new insights into the mechanism of cervical cancer radioresistance and indicate that targeting the HMGB3/hTERT signaling axis may benefit cervical cancer patients.

This study investigated the factors that caused the differences in egg production during the development of ovarian follicles in Leizhou black ducks. Leizhou black ducks population was divided into 2 groups as high-yield group (HG) and low-yield group (LG). The number of eggs (NE), age at first egg (AFE), weight at first egg, and egg weight (EW) of both groups were recorded, and differences were analyzed using the t test. The logistic model was used to simulate the egg production curves to analyze the production rules. The ovarian follicles of both duck groups were collected to count the number of different grades sized follicles, weigh the ovaries, and observe follicular sections to analyze the developmental differences. Ovarian transcriptomic sequencing was performed to investigate differentially expressed genes and signal pathways in both duck groups. The results revealed a significant difference (P

ABSTRACT: Our previous study on the ovarian transcriptomic analysis in Leizhou black duck revealed that the ESR2 gene was involved in hormone regulation in reproduction and the estrogen signaling pathway related to reproductive performance was enriched. This suggested that ESR2 may have a functional role in the reproductive performance of the Leizhou black duck. Thus, this study aimed at evaluating the polymorphism of the ESR2 gene and its association with egg-laying traits and the distribution pattern of ESR2 mRNA in laying and non-laying Leizhou black ducks. In this study, genomic DNA was extracted from blood samples of 101 Leizhou black ducks to identify single nucleotide polymorphisms (SNPs) of the ESR2 gene to elucidate molecular markers highly associated with egg-laying traits. Four each of laying and non-laying Leizhou black ducks were selected to collect different tissues to analyze the ESR2 gene expression. A total of 23 SNPs were identified and association analysis of the single SNP sites showed that SNPs g.56805646 T>C and exon 3-20G>A were significantly (P < 0.05) associated with egg weight. Ducks with CT and AG genotypes had significantly higher (P < 0.05) egg weights than their respective other genotypes. Haplotype association analysis of g.56805646 T>C and exon 3-20G>A showed that the haplotypes were significantly associated with egg weight. Higher egg weight was seen in individuals with H3H4 haplotypes. In the hypothalamus-pituitary-gonadal (HPG) axis, the results of qRT/PCR showed that ESR2 mRNA was significantly (P < 0.05) expressed in the ovaries of both duck groups than in the hypothalamus and pituitary. In the oviduct, ESR2 was significantly (P < 0.05) higher in the infundibulum and magnum of laying and non-laying ducks respectively. This study provides a molecular marker for selecting Leizhou black ducks for egg production. In addition, it offers theoretical knowledge for studying the related biological functions of the ESR2 gene at the cellular level.

In complex electromagnetic environments, a clutter covariance matrix is required to estimate in the on-line manner, so as to adaptively adjust the filter weight to effectively suppress clutter, thereby improving target estimation, detection, location, and tracking. In this paper, a non-Gaussian clutter model is considered, while apart of the clutter data maybe contaminated by subspace interference, wherein the signal of interest is located in the subspace. To this end, we propose a knowledge-aided hierarchical Bayesian model and obtain the approximated posterior distribution of the clutter covariance matrix by exploiting variational Bayesian inference methods. The target detection performance can be enhanced using a clutter-suppression filter that is designed based on the posterior mean of the clutter covariance matrix. A comparison of the computer simulation results with real clutter data confirms that the proposed method can suppress the clutter and improve detection performance.