ObjectiveTo explore the establishment of performance assessment indicators for the classification and grading of public health staff in district-level Centers for Disease Control and Prevention (CDCs), and to provide a basis for such evaluations. MethodsThrough literature review and group interviews, performance evaluation indicators were developed based on competency evaluation. Experts were invited to evaluate the weight of performance evaluation indicators for public health staff from different categories, with the average value used to represent the weight of each indicator. ResultsTwenty-nine experts from universities in Shanghai, municipal CDCs, and district CDCs participated, yielding an expert authority coefficient of 0.86. The performance evaluation indicators for department managers were categorized into three levels, with 4 indicators at the primary level, 16 indicators at the secondary level, and 42 indicators at the tertiary level, while those for general staff included 4 primary indicators, 15 secondary indicators, and 36 tertiary indicators. Significant differences were observed in the weight coefficients of the primary indicators (internal operations, professional work, and learning and growth) between department managers and general staff. The top three secondary indicators for department managers were department management, monitoring and prevention, and level of expertise. For mid-level and senior staff, the top three secondary indicators were monitoring and prevention, level of expertise, and research work. The top three secondary indicators for junior staff were monitoring and prevention, professional expertise, and professional attitude. No significant statistical differences were found among tertiary indicators. ConclusionThe developed performance evaluation indicators are reliable. Staff at different levels and classifications should be evaluated using different performance evaluation standards to accurately reflect individual performance and contributions.

Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1^OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1^OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
Humans ; Arthritis, Rheumatoid/genetics* ; Macrophages/immunology* ; Fibroblasts/metabolism* ; Phenotype ; Extracellular Matrix Proteins/genetics* ; Proteoglycans/genetics* ; Synovial Membrane/cytology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; Nitric Oxide Synthase Type II/genetics* ; Cell Differentiation ; Coculture Techniques ; THP-1 Cells

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

ObjectiveTo investigate the effect and mechanism of salvianolic acid B combined with puerarin in protecting the SH-SY5Y cells from the damage by oxygen-glucose deprivation/reoxygenation （OGD/R） based on pyroptosis. MethodSH-SY5Y cells were used to establish the model of OGD/R， and cells were classified into the control， OGD/R， 10 μmol·L^-1 salvianolic acid B， 100 μmol·L^-1 puerarin， 10 μmol·L^-1 salvianolic acid B + 100 μmol·L^-1 puerarin， and 10 μmol·L^-1 NOD-like receptor protein 3 （NLRP3） inhibitor MCC950 groups. Except the control group， other groups were rapidly reoxygenated for 12 h after 6 h OGD for modeling. The cell survival rate was determined by the methyl thiazolyl tetrazolium （MTT） assay. An optical microscope was used to observe the cell morphology. A spectrophotometer was used to determine the content of lactic dehydrogenase （LDH） in culture supernatant. Cell damage was measured by Hoechst/PI staining. The mRNA levels of NLRP3， cysteinyl aspartate specific proteinase-1 （Caspase-1）， gasdermin D （GSDMD）， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β） were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein activation of Caspase-1 and NLRP3 was detected by immunofluorescence. Western blot was employed to determine the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1. ResultCompared with the control group， the OGD/R group showed decreased cell survival rate （P<0.01）， damaged cell morphology， increased leakage rate of LDH （P<0.01）， up-regulated mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.01）， and up-regulated protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.01）. Compared with the OGD/R group， salvianolic acid B， puerarin， and salvianolic acid B combined with puerarin improved cell survival rate （P<0.01）， and the combined treatment group outperformed salvianolic acid B and puerarin used alone （P<0.01）. Salvianolic acid B combined with puerarin and MCC950 both improved cell morphology， reduced the leakage of LDH （P<0.01）， alleviated cell damage， and down-regulated the mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.05， P<0.01） and also the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.05， P<0.01）. ConclusionThe results indicated that salvianolic acid B combined with puerarin can alleviate the OGD/R-induced damage of SH-SY5Y cells by inhibiting pyroptosis.

OBJECTIVE To evaluate the global cancer-associated thromboembolism risk assessment tools based on evidence- based methods， and to provide methodological reference and evidence-based basis for constructing a specific tool in China. METHODS A comprehensive search was conducted on 6 databases， including CNKI， Wanfang data， VIP， CBM， PubMed， and Embase， as well as on the websites of NCCN， ASCO， ESMO and so on with a deadline of June 30， 2022. Furthermore， a supplementary search was conducted in January 2023. The essential characteristics and methodological quality of included risk assessment tools were described and analyzed qualitatively， focusing on comparing each assessment stratification ability. RESULTS Totally 14 risk assessment tools were included in the study， with a sample size of 208-18 956 cases and an average age distribution of 53.1-74.0 years. The applicable population included outpatient cancer student@sina.com patients， lymphoma patients， and multiple myeloma patients，etc. The common predictive factors were body mass index， venous thromboembolism history， and tumor site. All tools had undergone methodological validation， with 9 presented in a weighted scoring format. Only seven tools were used simultaneously for specificity， sensitivity， negative predictive value （NPV）， positive predictive value （PPV） and area under the curve （AUC） or C statistical analysis. CONCLUSIONS The risk of bias in constructing existing tools is high， and the heterogeneity of tool validation results is significant. The overall methodological quality must be improved， and its risk stratification ability must also be investigated. There are still certain limitations in clinical practice in China.

The intestine is the main site of oral drug absorption, and the epithelial cells of the intestine contain villi and microvilli, which promote secretion, cell adhesion, and absorption by increasing surface area and other factors. Traditional two-dimensional/three-dimensional (2D/3D) cell culture models and animal models have played an important role in studying drug absorption, but their application is limited due to the lack of sufficient predictability of human pharmacokinetics or ethical issues, etc. Therefore, mimicking the core structure and key functions of the human intestine based on in vitro live cells has been the focus of research on constructing a microfluidic chip-based intestinal model. The model is a microfluidic chip bionic system that simulates the complex microstructure, microenvironment, and physiological functions of the human intestine using microfabrication technology. Compared with 2D cell culture and animal experiments, the intestinal microarray model can effectively simulate the human in vivo environment and is more specific in drug screening. The research progress and applications in disease modeling, drug absorption and transport of intestinal microarray models and intestine-related multi-organ coupled microarray models at home and abroad were reviewed in this paper. The current challenges of intestinal chip simulating intestinal homeostasis and diseases were summarized，in order to provide reference for the further establishment of a more reliable in vitro intestinal chip model.

Objective To analyze serum characteristics and determine the reference range for thyroid function among healthy 11～16 year-old teenagers in Xi'an in order to offer a theoretical basis for clinical diagnosis and therapy.Methods A sum of 1 378 healthy 11～16 year-old teenagers who met the inclusion criteria from the First Affiliated Hospital of the Air Force Medical University(Xijing Hospital)between January 2020 and December 2022 were selected as research subjects,including 628 males and 750 females.They were divided into three groups based on age:Group 1:11～＜13 year-olds(433 cases),Group 2:13～＜15 year-olds(425 cases),and Group 3:15～≤16 year-olds(520 cases).Differences in serum thyroid function indices among different genders and age groups were analyzed,the reference ranges for these indices were established,and 99 healthy 11-16 year-old teenagers who met the inclusion criteria were chosen for verification.Results There were no significant differences between different genders in thyroid stimulating hormone[TSH,2.56(1.80,3.63)μIU/ml vs 2.43(1.68,3.48)μIU/ml]and total thyroxine[TT4,97.84(85.34,111.00)nmol/L vs 98.20(87.16,111.23)nmol/L],the differences were statistically significant(Z=-1.881,-0.638,all P＞0.05).Meanwhile,the differences in free thyroxine[FT4,16.93(15.49,18.60)pmol/L vs 16.26(14.80,17.83)pmol/L],free triiodothyronine[FT3,6.21(5.66,6.80)pmol/L vs 5.59(4.98,6.19)pmol/L],and total triiodothyronine[TT3,2.24(1.96,2.55)nmol/L vs 2.04(1.78,2.34)nmol/L]between different genders were significant(Z=-5.368,-11.994,-6.417 all P＜0.01).The differences in thyroid function indices were significant among different age groups(Z=10.649～261.003,all P＜0.05).The reference ranges for thyroid function indices across different age groups and genders were established,in which thyroid function indicators were verified to be within the established reference range by 99 samples.Conclusion Teenage hormone secretion varies greatly,and the secretion of thyroid hormones is influenced by various factors.Thus,the diagnosis and treatment of teenage thyroid diseases cannot fully rely on the reference ranges provided by adults or manufacturers.This study established the reference range of the thyroid function indices of 11～16 year-old teenagers in Xi'an,offering clinical doctors'diagnosis and treatment data support.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.