Single-cell landscape of immunological responses in patients with COVID-19.

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.

Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients.

OBJECTIVE: A comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure. DESIGN: We performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation. RESULTS: Both IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell-cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores. CONCLUSION: Our study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies.

[Application of Animal Model Training in Preclinical Skills Teaching for Graduate Students of Dentistry].

Objective: To explore the potential application value of animal model training in improving the comprehensive clinical ability of postgraduate students of dentistry and to provide reference for new methods of preclinical skills teaching. Methods: A total of 40 postgraduate students of dentistry were assigned to two groups, an experimental group and a control group. The control group took the routine teaching course on root canal treatment for the right mandibular first molar, using a simulated model of human head. The experimental group also took a teaching course on root canal therapy for the right mandibular first molar, but an animal model was used for the group. After the course was completed, the instructor conducted comprehensive evaluation of the students' psychological quality, patient communication skills, diagnosis and treatment logic, speed of performing procedures, and treatment plan design. A questionnaire survey was conducted to examine the students' attitudes toward and evaluation of animal model training. Results: The scores for psychological quality (0.430±0.024 vs. 0.115±0.036), patient communication skills (0.878±0.065 vs. 0.115±0.036), diagnosis and treatment logic (0.630±0.066 vs. 0.372±0.033), speed of performing procedures (0.8975±0.019 vs. 0.055±0.080), and treatment plan design (0.539±0.036 vs. 0.396±0.017) of the experimental group were significantly higher than those of the control group ( P<0.0001). The total score of the experimental group (3.374±0.184) was significantly higher than that of the control group (1.053±0.082) and the difference was statistically significant ( P<0.001). 95% of the students in the control group and 100% of those in the experimental group were willing to participate in animal model training to improve their level of diagnosis and treatment skills for dental and endodontic diseases, showing no statistically significant difference ( χ 2=1.026, P=0.3112). In the experimental group, 30% of the students believed that their psychological qualities had been improved, 50% believed that their procedure skills had been improved, and 20% believed that animal model training had expanded the scope of their theoretical knowledge. Conclusion: Adding animal model training can improve dentistry graduate students' comprehensive abilities, including their psychological quality, patient communication skills, diagnosis and treatment logic, speed of performing procedures, and treatment plan design. In addition, it helps students familiarize themselves in advance with animal experimental operations for basic research, thus helping them acquire dual professional skills.

UPLC-MS/MS Method for Detection of Etomidate and Its Metabolite Etomidate Acid Quantity in Blood.

OBJECTIVES: To establish a method for the simultaneous quantitative analysis of etomidate and its metabolite etomidate acid in blood, and to discuss its application value in actual cases. METHODS: Acetonitrile precipitate protein method was used, and C18 column was selected. Gradient elution was performed with acetonitrile and 5 mmol/L ammonium acetate within 6 min. Electrospray ionization source in positive ion mode was used. The internal standard etomidate acid-d5 was obtained by etomidate-d5 alkaline hydrolysis reaction. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for quantitative analysis. The methodological verification was conducted. RESULTS: Etomidate and etomidate acid in blood showed good linear relationship in the quantitative linear range (r>0.999), with the lower limit of quantification was 2.5 ng/mL and 7.5 ng/mL, respectively. The accuracy, precision, recovery rate, and matrix effect of the method met the professional verification standards. The practical application results showed that etomidate and etomidate acid could be detected in the blood of the abusers, and their mass concentrations ranged from 17.24 to 379.93 ng/mL. CONCLUSIONS: The method established in this study can simultaneously quantify etomidate and etomidate acid in blood, which is simple and convenient to operate with accuracy. It can meet the detection needs of actual cases and provide technical support for law enforcement to crack down on etomidate abuse.

Evaluation of egg white hydrolysates on the hepatoprotective effect in vitro and in vivo.

The small molecule characteristics and nutritional value of egg white hydrolysates have been widely used. In the present study, in vitro and in vivo models were used to investigate the hepatoprotective effect of egg protein hydrolysate (EWH) by regulating the expression of antioxidant enzymes. The in vitro experiment results showed that 0.1, 0.5, and 1 mg/mL of EWH enhanced antioxidant activity in HepG2 cells by increased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels. The in vivo experiment results showed that EWH (L) (38.5 mg/kg BW) and EWH (H) (385 mg/kg BW) alleviated carbon tetrachloride (CCl4)-induced hepatotoxicity in SD rats through reduced levels of serum aspartate aminotransferase (AST) alanine aminotransferase (ALT), and lipid peroxidation products malondialdehyde (MDA). In addition, EWH also ameliorates CCl4-induced hepatotoxicity in SD rats by increasing the antioxidant activity of GSH levels with a decrease in oxidized glutathione (GSSG) levels. Besides, EWH ameliorates liver tissue injuries by CCl4-induction. EWH has the highest glutamic acid in free amino acid composition, the second highest was aspartic acid, and the third was cystine, 204, 141, and 125 mg/100 g, respectively. These results suggest EWH has hepatoprotective potential through reduced lipid peroxidation products and enhanced antioxidant activity.

Compromised long-lived memory CD8+ T cells are associated with reduced IL-7 responsiveness in HIV-infected immunological nonresponders.

Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long-lived memory CD8+ T cells (LLMCs) are essential executors of long-term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological nonresponders (INRs). We found that both TNs and INRs showed severely compromised LLMCs compared with HCs and CRs, respectively. The decrease of LLMCs in TNs correlated positively with the reduction of their precursors, namely memory precursor effector T cells (MPECs), which might be associated with elevated pro-inflammatory cytokines. Strikingly, INRs showed an accumulation of MPECs, which exhibited diminished responsiveness to interleukin 7 (IL-7), thereby indicating abrogated differentiation into LLMCs. Moreover, in vitro studies showed that treatment with dexamethasone could improve the IL7-phosphorylated (p)-signal transducer and activator of transcription (STAT5) response by upregulating the expression of the interleukin 7 receptor (IL-7Rα) on MPECs in INRs. These findings provide insights that will encourage the development of novel therapeutics to improve immune function in PLWH.

Dynamics of HIV reservoir decay and naïve CD4 T-cell recovery between immune non-responders and complete responders on long-term antiretroviral treatment.

BACKGROUND: The dynamics of viral reservoir decay and naïve CD4 T-cell recovery between immunological non-responders (INR) and complete responders (CR) during long-term antiretroviral treatment (ART) are not fully known. METHODS: Twenty-eight chronic HIV-infected individuals on 5-year ART were divided into two groups: INR (CD4 counts ≤350 cells/µL, n = 13) and CR (CD4 counts ≥500 cells/µL, n = 15). The levels of HIV DNA and cell-associated HIV RNA (CA-RNA), CD4 counts, naïve CD4 counts and their correlations were analyzed at baseline, years 1, 3 and 5 of ART between the two groups. Expression of PD-1 on CD4 T-cells was quantified by flow cytometry. Linear mixed effect models were used to estimate the change procession in repeated measurements over 5 years. Slopes of the above-mentioned indicators were estimated using participant-specific linear regressions, respectively. RESULTS: INR maintained higher levels of HIV DNA and CA-RNA with higher percentages of PD-1+CD4 T-cells compared with CR during 5-year ART, concurrent with lower naïve CD4 T-cells. However, the rates of HIV DNA and CA-RNA decay in INR were not different from that in CR over time, and INR had higher rates of naïve CD4 T-cell percentage recovery. The baseline levels of HIV DNA were positively associated with the 5-year levels of HIV DNA, but negatively associated with the 5-year naïve CD4 counts. CONCLUSIONS: INR maintained significantly higher viral reservoir and lower naïve CD4 T-cells compared with CR during 5-year ART, however, the rates of reservoir decay and naïve CD4 T-cell percentage growth within INR were not lower than that in CR over time.

Transforming growth factor-ß promotes the function of HIV-specific CXCR5+ CD8 T cells.

HIV replication can be inhibited by CXCR5+ CD8 T cells (follicular cytotoxic T cell [TFC]) which transfer into B-cell follicles where latent HIV infection persists. However, how cytokines affect TFC remain unclear. Understanding which cytokines show the ability to affect TFC could be a key strategy toward curing HIV. Similar mechanisms could be used for the growth and transfer of TFCs and follicular helper T (TFH) cells; as a result, we hypothesized that cytokines IL-6, IL-21, and transforming growth factor-ß (TGF-ß), which are necessary for the differentiation of TFH cells, could also dictate the development of TFCs. In this work, lymph node mononuclear cells and peripheral blood mononuclear cells from HIV-infected individuals were cocultured with IL-6, IL-21, and TGF-ß. We then carried out T-cell receptor (TCR) repertoire analysis to compare the differences between CXCR5- and CXCR5+ CD8 T cells. Our results showed that the percentage and function of TFC can be enhanced by stimulation with TGF-ß. Besides, TGF-ß stimulation enhanced the diversity of TCR and complementarity-determining region 3 sequences. HIV DNA showed a negative correlation with TFC. The use of TGF-ß to promote the expression of CXCR5+ CD8 T cells could become a new treatment approach for curing HIV.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17ß-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic reticulum, increased the mitochondrial Ca2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.

Identification of nitroimidazole-oxime derivatives targeting the polo-box domain of polo-like kinase 1.

Recent progress in the development of small molecular skeleton-derived polo-like kinase (PLK1) catalytic domain (KD) inhibitors has led to the synthesis of multiple ligands with high binding affinity. However, few systematic analyses have been conducted to identify key PLK1-PBD domain and characterize their interactions with potent PLK1 inhibitors. Therefore, we designed a series of PLK1-PBD inhibitors with an in silico scaffold modification strategy. A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. The biological profile of 4v suggests that this compound may be developed as a potential anticancer agent.

Broadly Conserved Fungal Effector BEC1019 Suppresses Host Cell Death and Enhances Pathogen Virulence in Powdery Mildew of Barley (Hordeum vulgare L.).

The interaction of barley, Hordeum vulgare L., with the powdery mildew fungus Blumeria graminis f. sp. hordei is a well-developed model to investigate resistance and susceptibility to obligate biotrophic pathogens. The 130-Mb Blumeria genome encodes approximately 540 predicted effectors that are hypothesized to suppress or induce host processes to promote colonization. Blumeria effector candidate (BEC)1019, a single-copy gene encoding a putative, secreted metalloprotease, is expressed in haustorial feeding structures, and host-induced gene silencing of BEC1019 restricts haustorial development in compatible interactions. Here, we show that Barley stripe mosaic virus-induced gene silencing of BEC1019 significantly reduces fungal colonization of barley epidermal cells, demonstrating that BEC1019 plays a central role in virulence. In addition, delivery of BEC1019 to the host cytoplasm via Xanthomonas type III secretion suppresses cultivar nonspecific hypersensitive reaction (HR) induced by Xanthomonas oryzae pv. oryzicola, as well as cultivar-specific HR induced by AvrPphB from Pseudomonas syringae pv. phaseolicola. BEC1019 homologs are present in 96 of 241 sequenced fungal genomes, including plant pathogens, human pathogens, and free-living nonpathogens. Comparative analysis revealed variation at several amino acid positions that correlate with fungal lifestyle and several highly conserved, noncorrelated motifs. Site-directed mutagenesis of one of these, ETVIC, compromises the HR-suppressing activity of BEC1019. We postulate that BEC1019 represents an ancient, broadly important fungal protein family, members of which have evolved to function as effectors in plant and animal hosts.

Impact of innovative immunization strategy on PCV13 vaccination coverage among children under 5 years in Weifang city, China: A retrospective study.

BACKGROUND: Pneumococcal Diseases (PDs) remains a serious public health problem around the world and in China. Pneumococcal vaccination is the most cost-effective measure to prevent PDs. In 2021, the government of Weifang City, Shandong Province, China introduced a free dose of domestic 13-valent Pneumococcal Conjugate Vaccine (PCV 13) to vaccinate registered children aged 6 months-2 years. This study aimed to evaluate the vaccination rate of PCV13 in children aged under 5 years before and after the vaccination program to provide evidences for further improving the prevention and control strategy for PDs. METHODS: We collected data from the children's vaccination information management system in Weifang City and analyzed the PCV13 vaccination coverage and characteristics in all vaccination clinics of Weifang City for children aged under 5 years. We compared the differences in vaccination rates by gender, birth year, manufacturer, and county before and after innovative immunization strategy. RESULTS: Among the included 593,784 children aged under 5 years, the PCV13 vaccination rate in Weifang was generally low before the innovative immunization strategy. Urban children had a higher PCV13 coverage than rural children (P < 0.001), and parents tended to vaccinate their children with imported PCV13.The full vaccination rate for domestic and imported PCV13 was 0.67 % and 1.70 %, respectively. After the vaccination program, the PCV13 coverage of children increased significantly in all counties within Weifang City (P < 0.001), especially for children above 12 months of age. Most parents preferred to vaccinate their children with domestic PCV13, and the full vaccination rate of domestic and imported PCV13 was 6.59 % and 0.16 %, respectively. CONCLUSIONS: The vaccination rate of PCV13 in children is still much lower than the global average, posting a severe health challenge that needs to be addressed thoroughly. To improve the prevention and control strategy for PDs, it is recommended to continue to explore other relevant incentives based on the innovative immunization strategy. Furthermore, it is also recommended that China should incorporate PCV13 into the National Immunization Programs (NIP) as soon as possible.

Host-induced gene silencing in barley powdery mildew reveals a class of ribonuclease-like effectors.

Obligate biotrophic pathogens of plants must circumvent or counteract defenses to guarantee accommodation inside the host. To do so, they secrete a variety of effectors that regulate host immunity and facilitate the establishment of pathogen feeding structures called haustoria. The barley powdery mildew fungus Blumeria graminis f. sp. hordei produces a large number of proteins predicted to be secreted from haustoria. Fifty of these Blumeria effector candidates (BEC) were screened by host-induced gene silencing (HIGS), and eight were identified that contribute to infection. One shows similarity to ß-1,3 glucosyltransferases, one to metallo-proteases, and two to microbial secreted ribonucleases; the remainder have no similarity to proteins of known function. Transcript abundance of all eight BEC increases dramatically in the early stages of infection and establishment of haustoria, consistent with a role in that process. Complementation analysis using silencing-insensitive synthetic cDNAs demonstrated that the ribonuclease-like BEC 1011 and 1054 are bona fide effectors that function within the plant cell. BEC1011 specifically interferes with pathogen-induced host cell death. Both are part of a gene superfamily unique to the powdery mildew fungi. Structural modeling was consistent, with BEC1054 adopting a ribonuclease-like fold, a scaffold not previously associated with effector function.

Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors.

An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (SCH 900229), a potent, PS1-selective γ-secretase inhibitor and clinical candidate for the treatment of Alzheimer's disease. Specifically, 4-CF(3) and 4-Br substituted arylsulfone analogs, (-)-1b and (-)-1c, are equipotent to compound (-)-1a. On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated.

Low-intensity ultrasound directly modulates neural activity of the cerebellar cortex.

BACKGROUND: Low-intensity ultrasound is a noninvasive neuromodulation technique with the potential to focally manipulate deep brain activity at millimeter-scale resolution. However, there have been controversies over the direct influence of ultrasound on neurons, due to an indirect auditory activation. Besides, the capacity of ultrasound to stimulate the cerebellum remains underestimated. OBJECTIVE: To validate the direct neuromodulation effects of ultrasound on the cerebellar cortex from both cellular and behavioral levels. METHODS: Two-photon calcium imaging were used to measure the neuronal responses of cerebellar granule cells (GrCs) and Purkinje cells (PCs) to ultrasound application in awake mice. And a mouse model of paroxysmal kinesigenic dyskinesia (PKD), in which direct activation of the cerebellar cortex leads to dyskinetic movements, was used to assess the ultrasound-induced behavioral responses. RESULTS: Low-intensity ultrasound stimulus (0.1 W/cm2) evoked rapidly increased and sustained neural activity in GrCs and PCs at targeted region, while no significant changes in calcium signals were observed responding to off-target stimulus. The efficacy of ultrasonic neuromodulation relies on acoustic dose modified by ultrasonic duration and intensity. In addition, transcranial ultrasound reliably triggered dyskinesia attacks in proline-rich transmembrane protein 2 (Prrt2) mutant mice, suggesting that the intact cerebellar cortex were activated by ultrasound. CONCLUSION: Low-intensity ultrasound directly activates the cerebellar cortex in a dose-dependent manner, and thus serves as a promising tool for cerebellar manipulation.

Advanced gastric cancer achieving major pathologic regression after chemoimmunotherapy combined with hypofractionated radiotherapy: A case report.

BACKGROUND: Currently, chemotherapy combined with immunotherapy is the established first-line standard treatment for advanced gastric cancer (GC). In addition, the combination of radiotherapy and immunotherapy is considered a promising treatment strategy. CASE SUMMARY: In this report, we present a case of achieving nearly complete remission of highly advanced GC with comprehensive therapies. A 67-year-old male patient was referred to the hospital because he presented with dyspepsia and melena for several days. Based on fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), endoscopic examination and abdominal CT, he was diagnosed with GC with a massive lesion and two distant metastatic lesions. The patient received mFOLFOX6 regimen chemotherapy, nivolumab and a short course of hypofractionated radiotherapy (4 Gy × 6 fractions) targeting the primary lesion. After the completion of these therapies, the tumor and the metastatic lesions showed a partial response. After having this case discussed by a multidisciplinary team, the patient underwent surgery, including total gastrectomy and D2 lymph node dissection. Postoperative pathology showed that major pathological regression of the primary lesion was achieved. Chemoimmunotherapy started four weeks after surgery, and examination was performed every three months. Since surgery, the patient has been stable and healthy with no evidence of recurrence. CONCLUSION: The combination of radiotherapy and immunotherapy for GC is worthy of further exploration.

A partially open conformation of an androgen receptor ligand-binding domain with drug-resistance mutations.

Mutations in the androgen receptor (AR) ligand-binding domain (LBD) can cause resistance to drugs used to treat prostate cancer. Commonly found mutations include L702H, W742C, H875Y, F877L and T878A, while the F877L mutation can convert second-generation antagonists such as enzalutamide and apalutamide into agonists. However, pruxelutamide, another second-generation AR antagonist, has no agonist activity with the F877L and F877L/T878A mutants and instead maintains its inhibitory activity against them. Here, it is shown that the quadruple mutation L702H/H875Y/F877L/T878A increases the soluble expression of AR LBD in complex with pruxelutamide in Escherichia coli. The crystal structure of the quadruple mutant in complex with the agonist dihydrotestosterone (DHT) reveals a partially open conformation of the AR LBD due to conformational changes in the loop connecting helices H11 and H12 (the H11-H12 loop) and Leu881. This partially open conformation creates a larger ligand-binding site for AR. Additional structural studies suggest that both the L702H and F877L mutations are important for conformational changes. This structural variability in the AR LBD could affect ligand binding as well as the resistance to antagonists.

Effect of different interventions on the efficacy of postpartum urinary incontinence in China: A systematic review and network meta-analysis.

BACKGROUND: Currently, numerous treatment measures exist for postpartum stress urinary incontinence (PSUI); however, the study results are inconsistent. METHOD: Computer searches of PubMed, Embase, Web of Science, CKNI, and Wanfang databases were conducted to search the literature on 13 different intervention modalities for PSUI from the date of establishment to January 2023 for analysis. The literature was independently screened, and the information was extracted by 2 researchers. A reticulated meta-analysis was conducted using Stata software. RESULTS: The findings of the reticulated meta-analysis revealed that, in terms of the effectiveness of the 13 interventions for treating PSUI from highest to lowest, the most effective was acupressure + pelvic floor muscle training (94.6%). Following this, the interventions ranked from best to worst were electroacupuncture + trans moxibustion (79.1%), pelvic floor muscle training + acupuncture (64.3%), pelvic floor muscle training + pelvic floor electrical stimulation (60.3%), biofeedback electrical stimulation + acupuncture (60.0%), pelvic floor muscle training + biofeedback electrical stimulation (59.8%), biofeedback electrical stimulation + acupuncture + herbal hot compresses (56.6%), moxibustion + pelvic floor muscle training (56.6%), pelvic floor muscle training + pelvic floor electrical stimulation + acupuncture (53.1%), biofeedback electrical stimulation + moxibustion (52.1%), pelvic floor muscle training (17.6%), biofeedback electrical stimulation (16.1%), and health coaching (0.2%). The evidence indicates that acupressure + pelvic floor muscle training may be the most effective intervention for treating PSUI occurrence. CONCLUSION: Improvement in 13 clinical indicators was observed in patients with PSUI, and significant enhancement was achieved through acupressure + pelvic floor muscle training.

Serum Copper Concentrations, Effect Modifiers and Blood Pressure: Insights from NHANES 2011-2014.

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74-1.42), 1.23 (0.88-1.72), and 1.08 (0.74-1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the ß (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was -0.92 (-2.07-0.23), -0.05 (-1.30-1.20), and -0.48 (-1.83-0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88-2.10), 1.35 (0.87-2.09), and 1.56 (0.98-2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97-1.37)-fold increased risk of hypertension in multivariable analysis (p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension.

The potential mechanism of the progression from latent to active tuberculosis based on the intestinal microbiota alterations.

INTRODUCTION: Tuberculosis (TB) poses a serious challenge to global health systems. The altered intestinal microbiota is associated with the pathogenesis of TB, but the exact links remain unclear. METHODS: 16 S rDNA sequencing was performed to comprehensively detect the changes in the intestinal microbiota of feces from active TB (ATB), latent TB infection (LTBI) and healthy controls (HC). RESULTS: The rarefaction curves demonstrated the sequencing results' validity. The alpha diversity was lowest in ATB, while highest in HC. Boxplot of beta diversity showed significant differences in every two groups. LDA Effect Size (LEfSe) Analysis revealed differences in probiotic bacteria like Romboutsia, Bifidobacterium and Lactobacillus in LTBI, and pro-inflammatory bacteria like R. gnavus, Streptococcus and Erysipelatoclostridium in ATB, corresponding to the cluster analysis. PICRUST2 analysis revealed the pentose phosphate pathway was active in ATB and LTBI (more active in ATB). The differences between the groups are statistically significant at the P<0.05 level. CONCLUSION: Our study indicated that from LTBI to ATB, some intestinal microbiota inhibit the synthesis of interferon (INF)-γ and interleukin (IL)-17, promoting the survival and spread of Mycobacterium tuberculosis (M. tb). In addition, the metabolites secreted by intestinal microbiota and dysbiosis in intestine also have an effect on the development of LTBI to ATB.