Analysis of risk factors for fatty liver disease in children with Wilson's disease.

BACKGROUND AND AIMS: Many children with Wilson's disease are complicated with dyslipidemia. The aim of this study was to investigate the risk factors for the development of fatty liver disease (FLD) in children with Wilson's disease. METHODS: We evaluated sex, age, weight, the disease course, treatment course, clinical classification, alanine transaminase (ALT), aspartate transaminase, γ-glutamyl transpeptidase, total biliary acid, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homocysteine, uric acid, fibrinogen (FBG), creatinine, procollagen III N-terminal propeptide, laminin, hyaluronic acid, type IV collagen, and performed receiver operating characteristic curve analysis to investigate the forecast value of individual biochemical predictors and combined predictive indicators to evaluate FLD in Wilson's disease. RESULTS: The multivariate logistic regression analysis revealed that ALT [odds ratio (OR), 1.011; 95% confidence interval (CI), 1.004-1.02; P  = 0.006], uric acid (OR, 1.01; 95% CI, 1.002-1.018; P  = 0.017), FBG (OR, 3.668; 95% CI, 1.145-13.71; P  = 0.037), creatinine (OR, 0.872; 95% CI, 0.81-0.925; P  < 0.001), and laminin (OR, 1.01; 95% CI, 1.002-1.018; P  = 0.017) acted as independent risk factors in Wilson's disease complicated with FLD. The receiver operating characteristic curves for combined predictive indicators demonstrated an area under the curve values of 0.872, which was found to be a significant predictors for FLD in Wilson's disease. CONCLUSIONS: We screened out the most important risk factors, namely ALT, uric acid, creatinine, FBG, and laminin for Wilson's disease complicated with FLD. The joint prediction achieved is crucial for identifying children with Wilson's disease complicated with FLD.

Impact of antifibrotic therapy on disease progression, all-cause mortality, and risk of acute exacerbation in non-IPF fibrosing interstitial lung diseases: evidence from a meta-analysis of randomized controlled trials and prospective controlled studies.

BACKGROUND: Nintedanib and pirfenidone are preferred pharmacological therapies for patients with idiopathic pulmonary fibrosis (IPF). However, evidence favoring antifibrotic therapy in patients with non-IPF fibrosing interstitial lung diseases (ILD) is limited. OBJECTIVE: To investigate the effects of antifibrotic therapy on disease progression, all-cause mortality, and acute exacerbation (AE) risk in patients with non-IPF fibrosing ILDs. DESIGN: Meta-analysis. DATA SOURCES AND METHODS: Electronic databases were searched for articles published before 28 February 2023. Studies that evaluated the efficacy of antifibrotic agents in patients with fibrosing ILDs were selected. The primary outcome was the disease progression risk, and the secondary outcomes included all-cause mortality and AE risk. The GRADE criteria were used for the certainty of evidence assessment. RESULTS: Nine studies with 1990 participants were included. Antifibrotic therapy reduced the rate of patients with disease progression (five trials with 1741 subjects; relative risk (RR), 0.56; 95% CI, 0.42-0.75; p < 0.0001; I2 = 0; high-certainty evidence). Antifibrotic therapy did not significantly decrease all-cause mortality (nine trials with 1990 subjects; RR, 0.76; 95% CI, 0.55-1.03; p = 0.08; I2 = 0; low-certainty evidence). However, in patients with progressive fibrosing ILDs (PF-ILD), antifibrotic therapy decreased all-cause mortality (four trials with 1100 subjects; RR, 0.69; 95% CI, 0.48-0.98; p = 0.04; I2 = 0; low-certainty evidence). CONCLUSION: Our study supports the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. TRIAL REGISTRATION: This study protocol was registered with PROSPERO (registration number: CRD42023411272).

Eucalyptol, limonene and pinene enteric capsules attenuate airway inflammation and obstruction in lipopolysaccharide-induced chronic bronchitis rat model via TLR4 signaling inhibition.

BACKGROUND: Chronic bronchitis (CB), a type of chronic obstructive pulmonary disease (COPD), poses a significant global health burden owing to its high morbidity and mortality rates. Eucalyptol, limonene and pinene enteric capsules (ELPs) are clinically used as expectorants to treat various respiratory diseases, including CB, but their acting mechanisms remain unclear. In this study, we investigated the anti-CB effects of ELP in a rat model of lipopolysaccharide (LPS)-induced CB. The molecular mechanisms underlying its inhibitory effects on airway inflammation were further explored in LPS-stimulated Beas-2B cells. METHODS: ELP was characterized using gas chromatography. The production of inflammatory mediators in bronchoalveolar lavage fluid (BALF) was determined using an enzyme-linked immunosorbent assay. The expression of MUC5AC, MUC5B, and p-p65 in the lung tissue was measured using immunohistochemical staining. The gene expression of inflammatory mediators was determined using qRT-PCR. The expression levels of the target proteins were detected by western blotting. Nuclear localization of p65 was determined using an immunofluorescence assay. RESULTS: Compared to the CB model rats, ELP-treated rats showed reduced airway resistance, inflammation, and goblet cell hyperplasia. In BALF, ELP decreased the levels of inflammatory mediators, including TNF-α, IL-6, MIP-1α, and CCL5. ELP also suppressed LPS-induced elevation of MUC5AC, MUC5B, and p-p65 in the lung tissue. The metabolic pathway changes caused by LPS challenge were improved by ELP treatment. In LPS-exposed Beas-2B cells, ELP treatment inhibited the expression of TNFA, IL6, CCL5, MCP1, and MIP2A and decreased the phospho-levels of toll-like receptor 4 (TLR4) signaling-related proteins, including p-p38, p-JNK, p-ERK, p-TBK1, p-IKKα/ß, p-IκB, p-p65, and p-c-Jun. ELP also hindered the nuclear translocation of p65, c-Jun, and IRF3. CONCLUSIONS: This study showed that ELP has a potential therapeutic effect in LPS-induced CB rat model, possibly by suppressing TLR4 signaling. These results justify the clinical use of ELP for the treatment of pulmonary inflammatory diseases.

Quantitative analysis of macular capillaries in diabetic patients using optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To quantify early changes of macular capillary parameters in type 2 diabetic patients using optical coherence tomography angiography(OCTA).METHODS: Retrospective case study. A total of 49 healthy subjects, 52 diabetic patients without retinopathy(noDR)patients, and 43 mild nonproliferative diabetic retinopathy(mNPDR)patients were recruited. Capillary perfusion density, vessel length density(VLD), and average vessel diameter(AVD)were calculated from macular OCTA images(3 mm×3 mm)of the superficial capillary plexus after segmenting large vessels and the deep capillary plexus. Parameters were compared among control subjects, noDR, and mNPDR patients. The area under the receiver operating characteristic curve estimated the abilities of these parameters to detect early changes of retinal microvascular networks.RESULTS: Significant differences were found in the VLD and AVD among the three groups(P&#x0026;#x003C;0.001). Compared with the control group, the noDR group had significantly higher AVD(P&#x0026;#x003C;0.05). VLD of both layers in patients of mNPDR group was significant decreased compared with that of noDR group(all P&#x0026;#x003C;0.01). Deep AVD had a higher area under the curve(AUC)of 0.796 than other parameters to discriminate the noDR group from the healthy group. Deep AVD had the highest AUC of 0.920, followed by that of the deep VLD(AUC=0.899)to discriminate the mNPDR group from the healthy group.CONCLUSIONS: NoDR patients had wider AVD than healthy individuals and longer VLD than mNPDR patients in both layers. When compared with healthy individuals, deep AVD had a stronger ability than other parameters to detect early retinal capillary impairments in noDR patients.

Genomic identification of cotton SAC genes branded ovule and stress-related key genes in Gossypium hirsutum.

SAC genes have been identified to play a variety of biological functions and responses to various stresses. Previously, SAC genes have been recognized in animals and Arabidopsis. For the very first time, we identified 157 SAC genes in eight cotton species including three diploids and five tetraploids with 23 SAC members in G. hirsutum. Evolutionary analysis classified all cotton SAC gene family members into five distinct groups. Cotton SAC genes showed conserved sequence logos and WGD or segmental duplication. Multiple synteny and collinearity analyses revealed gene family expansion and purifying selection pressure during evolution. G. hirsutum SAC genes showed uneven chromosomal distribution, multiple exons/introns, conserved protein motifs, and various growth and stress-related cis-elements. Expression pattern analysis revealed three GhSAC genes (GhSAC3, GhSAC14, and GhSAC20) preferentially expressed in flower, five genes (GhSAC1, GhSAC6, GhSAC9, GhSAC13, and GhSAC18) preferentially expressed in ovule and one gene (GhSAC5) preferentially expressed in fiber. Similarly, abiotic stress treatment verified that GhSAC5 was downregulated under all stresses, GhSAC6 and GhSAC9 were upregulated under NaCl treatment, and GhSAC9 and GhSAC18 were upregulated under PEG and heat treatment respectively. Overall, this study identified key genes related to flower, ovule, and fiber development and important genetic material for breeding cotton under abiotic stress conditions.

A case of Poirier-Bienvenu neurodevelopmental syndrome associated with CSNK2B gene shear variation and literature review / 中华神经科杂志

Objective:To summarize the clinical phenotype and genetic characteristics of Poirier-Bienvenu neurodevelopmental syndrome associated with CSNK2B gene variation. Methods:The clinical and genetic data of a child with Poirier-Bienvenu neurodevelopmental syndrome caused by shear variant of CSNK2B gene who was diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2022 were collected. Previous relevant literature at home and abroad was reviewed to summarize the clinical characteristics of the disease. Results:The child was a girl aged 13 months, mainly due to "intermittent convulsions for 2 months" for consultation. The clinical manifestations of the girl were normal face, generalized tonic-clonic seizures, low intelligence, language and motor retardation, and there was no abnormality in the long-range video electroencephalography and the head magnetic resonance imaging. No abnormality was found in chromosome karyotype analysis and chromosome coefficient of copy variation analysis. The whole exon gene sequencing test indicated that the child carried de novo heterozygous shear variant of CSNK2B gene c.291+5G>C, which had not been reported in the literature. According to the clinical manifestations and genetic examination results of the child, the diagnosis of Poirier-Bienvenu neurodevelopmental syndrome was clear. The CSNK2B gene of the proband′s parents and the twin sister was wild-type. The application of sodium valproate anti-seizure medication could effectively control the seizures of the child, and by giving rehabilitation function training, the child′s language and gross motor function was improved. Conclusions:The Poirier-Bienvenu neurodevelopmental syndrome is a rare autosomal dominant disorder caused by variants in the CSNK2B gene. The clinical manifestations are infancy-onset seizures, intellectual development disorders, language and motor development disorders, etc, and the video electroencephalogram and skull magnetic resonance are mostly normal. The CSNK2B gene shear variant is the genetic etiology of the proband.

Effects of modified posterior nasal nerve neurectomy combined with accessory posterior nasal nerve neurectomy on controlling intractable allergic rhinitis / 中南大学学报(医学版)

Objective: A subset of intractable allergic rhinitis (iAR) patients experience severe symptoms which cannot be effectively controlled by standard drug therapy and/or antigen specific immunotherapy. In recent decades, endoscopy vidian neurectomy and posterior nasal nerve neurectomy (PNNN) were introduced as treatments of iAR that have shown to be highly successful at symptom management in a number of patients. But some patients experience relapse or suboptimal symptom control postoperation. To improve the effectiveness of PNNN to control iAR, a modified PNNN surgical approach (mPNNN) combined with accessory posterior nasal nerve neurectomy (aPNNN), which called as mPNNN-aPNNN was used. This study aims to compare the effects between mPNNN-aPNNN and PNNN on controlling the symptoms of iAR and evaluate the surgical effectiveness and safety of mPNNN-aPNNN. Methods: The patients with iAR experienced mPNNN-aPNNN or PNNN surgery at the department of Otolaryngology Head and Neck Surgery of the Second Xiangya Hospital, Central South University from January 2018 to December 2019 were analyzed retrospectively. The approach of PNNN, a selective resection of the posterior nasal nerve branches, was modified to the neurectomy of total branches of posterior nasal nerve at the sphenopalatine foramen, and combined the operation of aPNNN in which the accessory posterior nasal nerve at the palatine bone perpendicular plate was resect in our study. Daily Nasal Symptom Scores (DNSS), Total Rhinitis Medication Score (TRMS), and the Rhinoconjunctivitis Qualities of Life Questionnaires Scores (RQLQS) were used to evaluate the complications during the operation and after the operation at the 3rd, 6th, 12th, and 24th month postoperatively. Total Nasal Symptom Scores (TNSS) was used to assess the total effective rate and markedly effective rate of the operations. Results: A total of 140 iAR patients experienced mPNNN-aPNNN or PNNN. Those with concomitant septoplasty and/or inferior turbinate reduction, and were absent during the postoperative follow-up were excluded. The final 62 patients with mPNNN-aPNNN and 34 with PNNN were enrolled. DNSS, TNSS, TRMS, and RQLQS at the postoperation were significantly improved compared with the preoperation in all patients (all P<0.001). Compared with PNNN, the postoperative DNSS, TNSS, and TRMS of mPNNN-aPNNN were obviously improved (all P<0.001). There was a persisted relief of symptoms at the postoperation in all patients with mPNNN-aPNNN. The total effective rate and markedly effective rate at the postoperative 24th month were 100％ and 83.3％, respectively. Furthermore, the postoperative RQLQS decreased significantly (P<0.001). Only 5 sides of all patients (5/192, 2.6％) reported upper palate numbness during the first week after operation, with all recovered spontaneously in 1 month without treatment. No other postoperative complications occurred in mPNNN-aPNNN and PNNN.Conclusion: The surgery of mPNNN-aPNNN improve TNSS more significantly than PNNN. The operation of mPNNN-aPNNN is safe and effective to control iAR symptoms.

The expression and significance of Piezo1 in chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To explore the expression and importance of Piezo1, E-cadherin, and Vimentin in nasal polyps patients. Methods:Thirty-five patients undergoing endoscopic sinus surgery under general anesthesia were streamed into 20 cases of nasal polyps（NP group） and 15 cases of simple septoplasty without any sinus disease（Control group）. Immunofluorescence staining and Western Blot were applied to detect the protein level of Piezo1, E-cadherin, and Vimentin in NP tissues and nasal polyp-derived primary human nasal epithelial cells（pHNECs）. Also, BEAS-2B cell lines were treated with human TGF-β1 protein to establish epithelial mesenchymal transition（EMT） model in vitro and quantitative real-time polymerase chain reaction were used to calculate Piezo1 and above biomarkers in the model. Results:Compared with control group, Piezo1 and Vimentin showed higher level while E-cadherin was lower in NP tissues and pHNECs.In EMT model in vitro, Piezo1 and Vimentin were demonstrated higher expression with decreased level of E-cadherin. Conclusion:The tendency of Piezo1 is consistent with the mesenchymal-related biomarker Vimentin, going against with epithelial-related biomarker E-cadherin, implying its involvement with EMT process in nasal polyps.

Role of androgen receptors in the development of hepatocellular carcinoma / 上海预防医学

Hepatocellular carcinoma （HCC） has emerged as a significant public health concern， posing a serious threat to the lives and health of residents in China. Furthermore， the incidence and mortality rates of HCC are notably higher in males than in females. Androgen receptors （AR） can contribute to the occurrence of male-specific cancers such as prostate cancer， suggesting a potential link to the increased susceptibility of males to HCC. Elucidating the cancer-promoting mechanism of AR and developing specific targeted interventions are effective ways to advance tertiary prevention of HCC and improve patient prognosis. This paper reviews the relevant evidence of AR’s role in promoting the occurrence and development of HCC， summarizes relevant mechanisms discovered to date， including promoting the stemness of HCC cells， altering the immune microenvironment， regulating key signaling pathways， inducing glycolysis in hepatocellular carcinoma， and synergizing with hepatitis B virus to promote HCC. Additionally， research directions for targeted interventions in HCC through AR-related signaling pathways are discussed.

Study on in vitro differentiation of human adenoid-derived mesenchymal stem cells into olfactory sensory neurons / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the feasibility of isolation and culture of human adenoid-derived mesenchymal stem cells (aMSCs) in vitro, and to observe the differentiation of aMSCs into olfactory sensory neurons. Methods: Adenoid tissues surgically removed from children with adenoid hypertrophy in the Second Xiangya Hospital of Central South University from September to November of 2020 were collected. The adenoid tissues were digested and isolated by trypsin and then cultured with adhesion method. The expressions of cell surface antigens CD45, CD73 and CD90 on aMSCs of P5 generation were tested by flow cytometry, and the ability of osteogenic and adipogenic induction were used to identify cell differentiation ability. Then, aMSCs were induced into differentiation by retinoic acid (RA), sonic hedgehog (SHH), basic fibroblast growth factor (bFGF), RA+SHH, RA+bFGF, SHH+bFGF and RA+SHH+bFGF, respectively. The morphology of differentiated cells was observed under inverted microscope. The expression of β-tubulin 3, which was the specific marker of sensory neuron, the expressions of growth associated protein-43 (GAP43) and olfactory maker protein (OMP), which were the specific markers of olfactory sensory neuron, were detected by immunofluorescence antibody assay. The expression intensities were compared by Chi-square test of four-grid table data. Results: aMSCs were successively isolated and cultured from human adenoid tissues. P0 cells generation had good adhesion and proliferation performance. P2 cells were basically purified. P5 cells expressed CD73 and CD90 with the purity of 99.3% and 99.75% respectively, without CD45 expression. P5 cells had a good ability of osteogenic differentiation and adipogenic differentiation. Neuron-like morphology and expression of β-tubulin 3 were found in differentiated cells after induced by RA, SHH, or bFGF, respectively. An induction of expression of GAP43 was found in differentiated cells of bFGF+SHH group and RA+SHH+bFGF group, without expression of OMP of each group. The intensity of GAP43 expression of RA+SHH+bFGF group was stronger than that of bFGF+SHH group (χ2=17.48, P<0.005). Conclusions: aMSCs can be cultured from human adenoid tissues, with the stably passaged and good differentiation ability. As a new population of mesenchymal stem cells, aMSCs have the neuroregenerative properties and could differentiate into immature olfactory sensory neurons under the induction of RA+SHH+bFGF in vitro.

Study on the mechanism of haitongpi prescription extract ointment in the treatment of knee osteoarthritis based on transcriptome / 中国骨伤

OBJECTIVE@#To explore the mechanism of Haitongpi Prescription extract in the treatment of knee osteoarthritis based on transcriptome.@*METHODS@#Total of 12 SPF grade rats were divided into control group(group C), model group(group M), and Haitongpi prescription group(group HP). The knee osteoarthritis rat model was established using the Panicker method for group M and group HP, and group HP was intervened by local topical application of Haitongpi Prescription extract for 4 weeks. Total RNA from mouse knee cartilage was extracted and three sets of differential genes were obtained through sequencing.Differential genes were prediction and analysis through GO function and KEGG pathway enrichment analysis.@*RESULTS@#A total of 109 differentially expressed genes were identified in Group C versus Group M, while 118 differentially expressed genes were identified in Group M versus Group HP, resulting in a total of 28 genes. GO functional enrichment analysis showed that the mechanism of HP extract in treating knee osteoarthritis mainly involved immunoglobulin mediated immune response, immunoglobulin complexes, and antigen binding; KEGG pathway enrichment analysis showed correlation with tumor necrosis factor (TNF) signaling pathway, interleukin 17(IL-17) signaling pathway, and estrogen signaling pathway.@*CONCLUSION@#HP extract can exert therapeutic effects on knee osteoarthritis through mechanisms such as immunoglobulin mediated immune response, immunoglobulin complexes, and antigen binding, as well as signaling pathways such as TNF signaling pathway, IL-17 signaling pathway, and estrogen signaling pathway.

Catalpol relieved angiotensin II-induced blood-brain barrier destruction via inhibiting the TLR4 pathway in brain endothelial cells.

CONTEXT: Catalpol is a major bioactive constituent of Rehmannia glutinosa Libosch (Scrophulariaceae), a traditional Chinese medicine, which is widely used in multiple diseases, including hypertension. OBJECTIVES: To explore whether catalpol protects against angiotensin II (Ang II)-triggered blood-brain barrier (BBB) leakage. MATERIALS AND METHODS: The bEnd.3 cells and BBB models were pre-treated with or without catalpol (50, 200 and 500 µM) or TAK-242 (1 µM) for 2 h and then with Ang II (0.1 µM) or LPS (1 µg/mL) for 24 h. Cell viability was determined by the MTT assay. The levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), caveolin-1 (Cav-1) and p-eNOS/eNOS were tested by western blot. The BBB permeability was evaluated by the flux of bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) across monolayers. nuclear factor kappa-B (NF-κB) p65 nuclear translocation was explored by immunofluorescence staining. RESULTS: Ang II (0.1 µM) decreased the cell viability to 86.52 ± 1.79%, elevated the levels of TLR4, MyD88, iNOS, TNF-α and Cav-1 respectively to 3.7-, 1.5-, 2.3-, 2.2- and 2.7-fold, reduced the level of p-eNOS/eNOS to 1.6-fold in bEnd.3 cells, and eventually increased BBB permeability. Catalpol dose-dependently reversed these changes at 50-500 µM. Meanwhile, catalpol (500 µM) inhibited the upregulated levels of TLR4 pathway-related proteins and NF-κB p65 nuclear translocation, decreased the enhanced transcytosis, and relieved the BBB disruption caused by both LPS (the TLR4 activator) and Ang II. The effects are same as TAK-242 (the TLR4 inhibitor). CONCLUSIONS: Catalpol relieved the Ang II-induced BBB damage, which indicated catalpol has high potential for the treatment of hypertension-induced cerebral small vessel disease (cSVD).

The protective effects of hyperoside on Ang II-mediated apoptosis of bEnd.3 cells and injury of blood-brain barrier model in vitro.

BACKGROUND: Hypertension and its associated dysfunction of the blood-brain barrier (BBB) are considered to contribute to cerebral small vessel disease (cSVD). Angiotensin II (Ang II), as an important vasoactive peptide of the renin-angiotensin system (RAS), is not only a pivotal molecular signal in hypertension, but also causes BBB leakage, cSVD and its related cognitive impair. Hyperoside (Hyp), a flavone glycoside, has antioxidant, antiphlogistic and anti-apoptosis effects. In this study, we investigate the protection of Hyp on apoptosis of bEnd.3 cells and BBB disruption in vitro induced by Ang II. METHODS: We used bEnd.3 cells to imitate a BBB monolayer model and explored the protection of Hyp on Ang II-induced BBB leakage. The apoptotic activity was assessed by TUNEL staining and flow cytometry. The expression of apoptosis pathway related proteins, tight junction proteins and transcytosis related proteins were detected by western blot assay. The BBB model permeability was detected through measuring the flux of sodium fluorescein (Na-F). RESULTS: We found that Hyp can not only effectively inhibit the apoptosis of bEnd.3 induced by Ang II, but also protect the structural soundness and functional integrity of BBB model by affecting the expression levels of junctional adhesion molecule A (JAM-A), Claudin-5, zonula occludens-1 (ZO-1), Caveolin-1 (Cav-1) and major facilitator superfamily domain-containing protein 2a (Mfsd2a). CONCLUSION: Hyp might be a potent compound for preventing Ang II-induced BBB disruption.

Revisiting the Transcriptome Landscape of Pig Embryo Implantation Site at Single-Cell Resolution.

Litter size is one of the most economically important traits in commercial pig farming. It has been estimated that approximately 30% of porcine embryos are lost during the peri-implantation period. Despite rapid advances over recent years, the molecular mechanism underlying embryo implantation in pigs remains poorly understood. In this study, the conceptus together with a small amount of its surrounding endometrial tissues at the implantation site was collected and subjected to single-cell RNA-seq using the 10x platform. Because embryo and maternal endometrium were genetically different, we successfully dissected embryonic cells from maternal endometrial cells in the data according to single nucleotide polymorphism information captured by single-cell RNA-seq. Undoubtedly, the interaction between trophoblast cells and uterine epithelial cells represents the key mechanism of embryo implantation. Using the CellChat tool, we revealed cell-cell communications between these 2 cell types in terms of secreted signaling, ECM-receptor interaction and cell-cell contact. Additionally, by analyzing the non-pregnant endometrium as control, we were able to identify global gene expression changes associated with embryo implantation in each cell type. Our data provide a valuable resource for deciphering the molecular mechanism of embryo implantation in pigs.

Research Progress on the Application of Human Oral Microbiome in Forensic Individual Identification / 法医学杂志

The oral cavity is the second largest microbial bank in humans after the intestinal canal, colonizing a large number of microorganisms including viruses, bacteria, archaea, fungi and protozoa. The great number of microbial cells, good DNA stability, and individual has a unique microbial community, these characteristics make the human microbiome expected to become a new biomarker for forensic individual identification. This article describes the characteristics of human oral microorganisms and microbial molecular markers in detail, analyzes the potential application value of microorganisms in forensic individual identification, and reviews the research progress of human oral microorganisms in forensic individual identification.

Research progress on the effects of various macro and trace elements on fluorosis / 中华地方病学杂志

Endemic fluorosis is a common biogeochemical disease. Although the etiology is clear, its molecular mechanism is not fully understood. So far, there is no specific method to effectively treat fluorosis, mainly to prevent. In recent years, a large number of studies have confirmed that a variety of macro elements such as calcium, magnesium, phosphorus, and trace elements such as selenium and boron play a positive regulatory role in the occurrence and development of fluorosis, and have different degrees of influence in the body's antagonism against fluorosis. High levels of trace elements such as arsenic, lead, aluminum and chromium are risk factors for fluorosis. In view of the importance of a variety of macro and trace elements in human nutrition and health, this article reviews the latest developments in multiple elements and fluorosis, especially skeletal fluorosis and dental fluorosis, in order to further understand the causes of fluoride-induced health damage, and provide theoretical reference for improving the prevention strategies of fluorosis in a targeted manner.

Clinical observation on Tongdu Tiaoqi acupuncture combined with warming acupuncture for postoperative urinary retention / 中国针灸

OBJECTIVE@#To compare the therapeutic effect of Tongdu Tiaoqi acupuncture (acupuncture for unblocking governor vessel and regulating qi ) combined with warming acupuncture, Tongdu Tiaoqi acupuncture, abdominal moxibustion and oral tamsulosin hydrochloride sustained release capsule on postoperative urinary retention.@*METHODS@#A total of 120 patients with postoperative urinary retention were randomized into an acupuncture-moxibustion group, an acupuncture group, a moxibustion group and a medication group, 30 cases in each group. Tongdu Tiaoqi acupuncture combined with warming acupuncture were applied in the acupuncture-moxibustion group. Tongdu Tiaoqi acupuncture was applied at Baihui (GV 20), Shuigou (CV 26) etc. in the acupuncture group. Moxibustion was applied at Qihai (CV 6), Guanyuan (CV 4), Shuidao (ST 28) and Sanyinjiao (SP 6) in the moxibustion group. Tamsulosin hydrochloride sustained release capsule was given orally in the medication group. The treatment was once a day, and 5-day treatment was required in each group. Before and after treatment, the residual urine volume of bladder, the visual analogue scale (VAS) score and the time of first urethral catheter removal were observed, and the clinical efficacy was compared in the 4 groups.@*RESULTS@#After treatment, the residual urine volume of bladder was decreased compared before treatment in the 4 groups (P<0.05), and that in the acupuncture-moxibustion group was less than the other 3 groups (P<0.05). After treatment, the VAS scores were decreased compared before treatment in the acupuncture-moxibustion group, the acupuncture group and the moxibustion group (P<0.05), and those in the 3 groups were lower than the medication group (P<0.05). The time of first urethral catheter removal in the acupuncture-moxibustion group was earlier than the other 3 groups (P<0.05). The total effective rate was 93.3% (28/30) in the acupuncture-moxibustion group, which was superior to 63.3% (19/30) in the acupuncture group, 60.0% (18/30) in the moxibustion group and 66.7% (20/30) in the medication group (P<0.05).@*CONCLUSION@#The therapeutic effect of Tongdu Tiaoqi acupuncture combined with warming acupuncture on postoperative urinary retention is superior to simple acupuncture, abdominal moxibustion and tamsulosin hydrochloride sustained release capsule.

Reliably Assessing Duration of Protection for COVID-19 Vaccines

Decision-making about booster dosing for COVID-19 vaccine recipients hinges on reliable methods for evaluating the longevity of vaccine protection. We show that modeling of protection as a piecewise linear function of time since vaccination for the log hazard ratio of the vaccine effect provides more reliable estimates of vaccine effectiveness at the end of an observation period and also more reliably detects plateaus in protective effectiveness as compared with the traditional method of estimating a constant vaccine effect over each time period. This approach will be useful for analyzing data pertaining to COVID-19 vaccines and other vaccines where rapid and reliable understanding of vaccine effectiveness over time is desired.

Effectiveness of Covid-19 Vaccines in the United States Over 9 Months: Surveillance Data from the State of North Carolina

BackgroundThe duration of protection afforded by Covid-19 vaccines in the United States is unclear. Whether the recent increase of breakthrough infections was caused by waning immunity to the primary vaccination or by emergence of new variants that are more highly transmissible is also unknown. MethodsWe extracted data on vaccination histories and clinical outcomes (Covid-19, hospitalization, death) for the period from December 13, 2020 through September 8, 2021 by linking data from the North Carolina COVID-19 Surveillance System and COVID-19 Vaccine Management System covering [~]10.6 million residents statewide. We used the Kaplan-Meier method to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen) vaccines in reducing the incidence of Covid-19 over successive post-vaccination time periods, producing separate estimates for individuals vaccinated during different calendar periods. In addition, we used Cox regression with time-dependent vaccination status and time-varying hazard ratios to estimate the effectiveness of the three vaccines in reducing the hazard rates or current risks of Covid-19, hospitalization, and death, as a function of time elapsed since the first dose. ResultsFor the Pfizer two-dose regimen, vaccine effectiveness in reducing the current risk of Covid-19 ramps to a peak level of 94.9% (95% confidence interval [CI], 94.5 to 95.2) at 2 months (post the first dose) and drops to 70.1% (95% CI, 68.9 to 71.2) after 7 months; effectiveness in reducing the current risk of hospitalization ramps to a peak level of 96.4% (95% CI, 94.7 to 97.5) at 2 months and remains at 87.7% (95% CI, 84.3 to 90.4) at 7 months; effectiveness in reducing the current risk of death ramps to 95.9% (95% CI, 92.9 to 97.6) at 2 months and is maintained at 88.4% (95% CI, 83.0 to 92.1) at 7 months. For the Moderna two-dose regimen, vaccine effectiveness in reducing the current risk of Covid-19 ramps to a peak level of 96.0% (95% CI, 95.6 to 96.4) at 2 months and drops to 81.9% (95% CI, 81.0 to 82.7) after 7 months; effectiveness in reducing the current risk of hospitalization ramps to a peak level of 97.5% (95% CI, 96.3 to 98.3) at 2 months and remains at 92.3% (95% CI, 89.7 to 94.3) at 7 months; effectiveness in reducing the current risk of death ramps to 96.0% (95% CI, 91.9 to 98.0) at 3 months and remains at 93.7% (95% CI, 90.2 to 95.9) at 7 months. For the Janssen one-dose regimen, effectiveness in reducing the current risk of Covid-19 ramps to a peak level of 79.0% (95% CI, 77.1 to 80.7) at 1 month and drops to 64.3% (95% CI, 62.3 to 66.1) after 5 months; effectiveness in reducing the current risk of hospitalization ramps to a peak level of 89.8% (95% CI, 78.8 to 95.1) at 2 months and stays above 80% through 5 months; effectiveness in reducing the current risk of death ramps to 89.4% (95% CI, 52.3 to 97.6) at 3 months and stays above 80% through 5 months. For all three vaccines, the ramping and waning patterns are similar for individuals who were vaccinated at different dates, and across various demographic subgroups (age, sex, race/ethnicity, geographic region, county-level vaccination rate). ConclusionsThe two mRNA vaccines are remarkably effective and durable in reducing the risks of hospitalization and death. The Janssen vaccine also offers a high level of protection against hospitalization and death. The Moderna vaccine is significantly more durable than the Pfizer vaccine in reducing the risk of Covid-19. Waning vaccine effectiveness is caused primarily by declining immunity rather than emergence of new variants. It would be worthwhile to investigate the effectiveness of the Janssen vaccine as a two-dose regimen, with the second dose given approximately 1-2 months after the first dose.

The protective effect of harpagoside on angiotensin II (Ang II)-induced blood-brain barrier leakage in vitro.

Hypertension and its associated dysfunction of the blood-brain barrier (BBB) contribute to cerebral small vessel disease (cSVD). Angiotensin II (Ang II), a vasoactive peptide of the renin-angiotensin system (RAS), is not only a pivotal molecular signal in hypertension but also causes BBB leakage, cSVD, and cognitive impair. Harpagoside, the major bioactive constituent of Scrophulariae Radix, has been commonly used for the treatment of multiple diseases including hypertension in China. The effect of harpagoside on Ang II-induced BBB damage is unclear. We employed an immortalized endothelial cell line (bEnd.3) to mimic a BBB monolayer model in vitro and investigated the effect of harpagoside on BBB and found that harpagoside alleviated Ang II-induced BBB destruction, inhibited Ang II-associated cytotoxicity in a concentration-dependent manner and attenuated Ang II-induced reactive oxygen species (ROS) impair by downregulation of Nox2, Nox4, and COX-2. Harpagoside prevented Ang II-induced apoptosis via keeping Bax/Bcl-2 balance, decreasing cytochrome c release, and inactivation of caspase-8, caspase-9, and caspase-3 (the mitochondria-dependent and death receptor-mediated apoptosis pathways). Moreover, harpagoside can alleviate Ang II-induced BBB damage through upregulation of tight junction proteins and decrease of caveolae-mediated endocytosis. Thus, harpagoside might be a potential drug to treat Ang II-induced cSVD.