Cathepsin S (CTSS) in IgA nephropathy: an exploratory study on its role as a potential diagnostic biomarker and therapeutic target.

Introduction: IgA nephropathy (IgAN), a prevalent form of glomerulonephritis globally, exhibits complex pathogenesis. Cathepsins, cysteine proteases within lysosomes, are implicated in various physiological and pathological processes, including renal conditions. Prior observational studies have suggested a potential link between cathepsins and IgAN, yet the precise causal relationship remains unclear. Methods: We conducted a comprehensive bidirectional and multivariable Mendelian randomization (MR) study using publicly available genetic data to explore the causal association between cathepsins and IgAN systematically. Additionally, immunohistochemical (IHC) staining and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate cathepsin expression levels in renal tissues and serum of IgAN patients. We investigated the underlying mechanisms via gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Molecular docking and virtual screening were also performed to identify potential drug candidates through drug repositioning. Results: Univariate MR analyses demonstrated a significant link between increased cathepsin S (CTSS) levels and a heightened risk of IgAN. This was evidenced by an odds ratio (OR) of 1.041 (95% CI=1.009-1.073, P=0.012) as estimated using the inverse variance weighting (IVW) method. In multivariable MR analysis, even after adjusting for other cathepsins, elevated CTSS levels continued to show a strong correlation with an increased risk of IgAN (IVW P=0.020, OR=1.037, 95% CI=1.006-1.069). However, reverse MR analyses did not establish a causal relationship between IgAN and various cathepsins. IHC and ELISA findings revealed significant overexpression of CTSS in both renal tissues and serum of IgAN patients compared to controls, and this high expression was unique to IgAN compared with several other primary kidney diseases such as membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis. Investigations into immune cell infiltration, GSEA, and GSVA highlighted the role of CTSS expression in the immune dysregulation observed in IgAN. Molecular docking and virtual screening pinpointed Camostat mesylate, c-Kit-IN-1, and Mocetinostat as the top drug candidates for targeting CTSS. Conclusion: Elevated CTSS levels are associated with an increased risk of IgAN, and this enzyme is notably overexpressed in IgAN patients' serum and renal tissues. CTSS could potentially act as a diagnostic biomarker, providing new avenues for diagnosing and treating IgAN.

Artificial neural network based on strong track and square root UKF for INS/GNSS intelligence integrated system during GPS outage.

When INS/GNSS (inertial navigation system/global navigation satellite system) integrated system is applied, it will be affected by the insufficient number of visible satellites, and even the satellite signal will be lost completely. At this time, the positioning error of INS accumulates with time, and the navigation accuracy decreases rapidly. Therefore, in order to improve the performance of INS/GNSS integration during the satellite signals interruption, a novel learning algorithm for neural network has been presented and used for intelligence integrated system in this article. First of all, determine the input and output of neural network for intelligent integrated system and a nonlinear model for weighs updating during neural network learning has been established. Then, the neural network learning based on strong tracking and square root UKF (unscented Kalman filter) is proposed for iterations of the nonlinear model. In this algorithm, the square root of the state covariance matrix is used to replace the covariance matrix in the classical UKF to avoid the filter divergence caused by the negative definite state covariance matrix. Meanwhile, the strong tracking coefficient is introduced to adjust the filter gain in real-time and improve the tracking capability to mutation state. Finally, an improved calculation method of strong tracking coefficient is presented to reduce the computational complexity in this algorithm. The results of the simulation test and the field-positioning data show that the proposed learning algorithm could improve the calculation stability and robustness of neural network. Therefore, the error accumulation of INS/GNSS integration is effectively compensated, and then the positioning accuracy of INS/GNSS intelligence integrated system has been improved.

MoS2@MWCNTs with Rich Vacancy Defects for Effective Piezocatalytic Degradation of Norfloxacin via Innergenerated-H2O2: Enhanced Nonradical Pathway and Synergistic Mechanism with Radical Pathway.

Molybdenum disulfide (MoS2)-based materials for piezocatalysis are unsatisfactory due to their low actual piezoelectric coefficient and poor electrical conductivity. Herein, 1T/3R phase MoS2 grown in situ on multiwalled carbon nanotubes (MWCNTs) was proposed. MoS2@MWCNTs exhibited the interwoven morphology of thin nanoflowers and tubes, and the piezoelectric response of MoS2@MWCNTs was 4.07 times higher than that of MoS2 via piezoresponse force microscopy (PFM) characterization. MoS2@MWCNTs exhibited superior activity with a 91% degradation rate of norfloxacin (NOR) after actually working 24 min (as for rhodamine B, reached 100% within 18 min) by pulse-mode ultrasonic vibration-triggered piezocatalysis. It was found that piezocatalysis for removing pollutants was attributed to the synergistic effect of free radicals (•OH and O2•-) and nonfree radical (1O2, key role) pathways, together with the innergenerated-H2O2 promoting the degradation rate. 1O2 can be generated by electron transfer and energy transfer pathways. The presence of oxygen vacancies (OVs) induced the transformation of O2 to 1O2 by triplet energy transfer. The fast charge transfer in MoS2@MWCNTs heterostructure and the coexistence of sulfur vacancies and OVs enhanced charge carrier separation resulting in a prominent piezoelectric effect. This work opens up new avenues for the development of efficient piezocatalysts that can be utilized for environmental purification.

IgM kappa proliferative glomerulonephritis with monoclonal immunoglobulin deposition complicated with nocardiosis dermatitis: a case report and review of literature.

Rationale: Monoclonal gammopathy of renal significance (MGRS) represents a group of disorders caused by monoclonal immunoglobulin (M protein) secreted by B cells or plasma cells. Proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID) is a glomerular disease and a form of MGRS. Here, we presented a rare case of a patient with IgM kappa PGNMID complicated with nocardiosis dermatitis. Patient concerns and diagnoses: A 56-year-old man was admitted to the hospital because of cutaneous purpura and proteinuria. His initial pathological diagnosis indicated membranous proliferative glomerulonephritis, IgM(++), and subacute interstitial nephritis. Based on further examination, he was finally diagnosed to have IgM kappa PGNMID and subacute interstitial nephritis. After the initial diagnosis, the patient received hormonal therapy. During the treatment, nocardiosis dermatitis emerged as a complication, and the hormonal therapy was gradually reduced. The patient refused further treatment with rituximab, and his health is currently stable. Outcomes: IgM kappa PGNMID complicated with nocardiosis dermatitis is an extremely rare occurrence. Laboratory examination and pathological analysis are required to confirm the diagnosis of this disorder. Timely and accurate diagnosis is essential for the appropriate treatment of PGNMID.

Hepatitis B Virus-Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape.

Hepatitis B viral (HBV) persistent infection plays a significant role in hepatocellular carcinoma (HCC) tumorigenesis. Many studies have revealed the pivotal roles of N6-methyladenosine (m6A) in multiple cancers, while the regulatory mechanism in stemness maintenance of HBV persistent infection-related HCC remains elusive. Here, we demonstrated that the level of m6A modification was downregulated by HBV in HBV-positive HCC, through enhanced stability of ALKBH5 mRNA. More specifically, we also identified that ALKBH5 mRNA was functionally required for the stemness maintenance and self-renewal in the HBV-positive HCC, but dispensable in HBV-negative HCC. Mechanistically, ALKBH5 demethylated the m6A modification in the 3' untranslated region of the oncogenic gene SNAI2 to prevent the recognition of YTHDF2 therewith stabilize SNAI2 transcripts, contributing to cancer stem cell traits in HBV-positive HCC. Moreover, the expression of SNAI2 reversed the suppression of stemness properties by knocking down ALKBH5. In addition, ALKBH5/SNAI2 axis accelerates tumor immune evasion through activated ligand of immune checkpoint CD155. Our study unveiled that the ALKBH5 induces m6A demethylation of the SNAI2 as a key regulator in HBV-related HCC, and identifies the function of ALKBH5/SNAI2/YTHDF2 axis in promoting the stem-like cells phenotype and immune escape during HBV infection. IMPLICATIONS: HBV promotes HCC stemness maintenance through elevate m6A modification of SNAI2 in an ALKBH5-YTHDF2-dependent manner and increases the expression of the ligand of immune checkpoint CD155.

Faecal hsa-miR-7704 inhibits the growth and adhesion of Bifidobacterium longum by suppressing ProB and aggravates hepatic encephalopathy.

Both gut microbiome and microRNAs (miRNAs) play a role in the development of hepatic encephalopathy (HE). However, the functional link between the microbiome and host-derived miRNAs in faeces remains poorly understood. In the present study, patients with HE had an altered gut microbiome and faecal miRNAs compared with patients with chronic hepatitis B. Transferring faeces and faecal miRNAs from patients with HE to the recipient mice aggravated thioacetamide-induced HE. Oral gavage of hsa-miR-7704, a host-derived miRNA highly enriched in faeces from patients with HE, aggravated HE in mice in a microbiome-dependent manner. Mechanistically, hsa-miR-7704 inhibited the growth and adhesion of Bifidobacterium longum by suppressing proB. B. longum and its metabolite acetate alleviated HE by inhibiting microglial activation and ammonia production. Our findings reveal the role of miRNA-microbiome axis in HE and suggest that faecal hsa-miR-7704 are potential regulators of HE progression.

Dual-state emission, mechanofluorochromism, and lipid droplet imaging of asymmetric D-π-A-D'-type triads.

Dual-state emission (DSE) is an emerging phenomenon wherein organic luminescent molecules display bright emissions in both molecularly isolated and packed states, addressing the challenge associated with the traditional paradigm of dyes with mono-state emission. This study presents the design and synthesis of two unsymmetrical triads, TPCA and TPCT, featuring a D-π-A-D' electronic structure by integrating phenothiazines, triphenylamines, and cyanostilbene. Photophysical assessments reveal that both molecules serve as robust DSEgens, exhibiting strong emissions in both solution and solid phases. TPCA displays ΦTHF 53.2% and Φsolids 43.2%, while TPCT exhibits ΦTHF 49.6% and Φsolids 37.5%. However, due to differences in molecular conformation and packing, they diverge in solid-state emission wavelengths and mechanofluorochromic behavior. In the solid state, TPCA emits strong red fluorescence, contrasting with TPCT, which emits orange fluorescence. Furthermore, TPCA demonstrates significant mechanofluorochromism (MFC), shifting from yellow to yellow-red upon mechanical grinding, while TPCT exhibits negligible MFC owing to conformational distinctions. As robust and low-toxic bioimaging agents, both TPCA and TPCT prove highly effective for lipid-droplet imaging studies. This research contributes valuable insights to the evolving field of DSE materials, elucidating the promising applications and mechanisms governing their versatile emission behaviors.

Complement C4d as a biomarker for systemic lupus erythematosus and lupus nephritis.

Background: Increasing studies in the last decade have led to the widespread understanding that C4d, a split product of complement component 4 (C4), is a potential biomarker for systemic lupus erythematosus (SLE) and lupus nephritis (LN).Purpose: The aim of this review is to summarize the highlights of studies investigating the use of C4d as a biomarker for diagnosing and monitoring SLE and LN patients.Data collection: we searched PubMed/Medline and Wanfang databases using the terms "C4d and systemic lupus erythematosus", "C4d and lupus nephritis", and "Complement C4d".Results: The deposition of C4d on circulating blood cells has been shown in several clinical studies to be a potential diagnostic marker that can be used to monitor patients with SLE. In addition, C4d deposits on circulating blood cells may be a helpful diagnostic marker for LN, one of the most severe complications of SLE. Meanwhile, studies utilizing renal biopsy specimens have indicated that C4d deposition in the renal peritubular capillaries of LN patients may predict more severe LN or a worse patient prognosis. Generally, a high plasma C4d level and a high plasma C4d/C4 ratio may also be promising indicators that can be used to monitor patients with SLE and LN.Conclusions: C4d detection may be a novel strategy for further clinical prediction and therapy.

The association between social integration and utilization of primary health care among migrants in China: a nationwide cross-sectional study.

BACKGROUND: Migrants is a large population in China. To improve the health and wellbeing of migrants is a critical policy and social issue in China, and to enhance the utilization of primary health care by migrants is one of the most important approaches in promoting equity in health. However, there exists little research about the association between social integration and the utilization of primary health care. To address the research gap, this research aims at exploring the relation between social integration and the utilization of primary health care among migrants in China. METHODS: Using the national data from China Migrants Dynamic Survey (CMDS) in 2017, 169,989 migrants were included in this study. Social integration was measured by social communication, acculturation and self-identity, with 8 indicators. The utilization of primary health care was measured by the receiving of health education on infectious diseases (ID) and noncommunicable diseases (NCD) as well as the first visit institution when migrants were sick. After the descriptive statistical analysis, binary logistic regression was employed to evaluate the association between social integration and the utilization of primary health care. RESULTS: 65.99% of the migrants received health education on infectious diseases (ID), 40.11% of the migrants received health education on noncommunicable diseases (NCD) and 8.48% of the migrants chose to go to Community Health Center (CHC) seeking for health services. There was a positive effect of social organization participation, the influence of hometown customs, differences of hygiene habits between migrants and local people, integration willingness and evaluation of identity on the receiving of health education on ID and NCD, as well as a positive effect of civil activities engagement and differences of hygiene habits between migrants and local people on the utilization of CHC after getting sick. CONCLUSIONS: Social integration was associated with the utilization of primary health care among migrants in China. Generally speaking, greater social integration was associated with higher possibility of receiving health education on ID and NCD. However, the effect of social integration on the utilization of CHC was more complex among different indicators. There should be more policy interventions to improve the social integration of migrant which help them to get familiar with the health resource available, as well as improve the capacity of CHC.

Target Genes of c-MYC and MYCN with Prognostic Power in Neuroblastoma Exhibit Different Expressions during Sympathoadrenal Development.

Deregulation of the MYC family of transcription factors c-MYC (encoded by MYC), MYCN, and MYCL is prevalent in most human cancers, with an impact on tumor initiation and progression, as well as response to therapy. In neuroblastoma (NB), amplification of the MYCN oncogene and over-expression of MYC characterize approximately 40% and 10% of all high-risk NB cases, respectively. However, the mechanism and stage of neural crest development in which MYCN and c-MYC contribute to the onset and/or progression of NB are not yet fully understood. Here, we hypothesized that subtle differences in the expression of MYCN and/or c-MYC targets could more accurately stratify NB patients in different risk groups rather than using the expression of either MYC gene alone. We employed an integrative approach using the transcriptome of 498 NB patients from the SEQC cohort and previously defined c-MYC and MYCN target genes to model a multigene transcriptional risk score. Our findings demonstrate that defined sets of c-MYC and MYCN targets with significant prognostic value, effectively stratify NB patients into different groups with varying overall survival probabilities. In particular, patients exhibiting a high-risk signature score present unfavorable clinical parameters, including increased clinical risk, higher INSS stage, MYCN amplification, and disease progression. Notably, target genes with prognostic value differ between c-MYC and MYCN, exhibiting distinct expression patterns in the developing sympathoadrenal system. Genes associated with poor outcomes are mainly found in sympathoblasts rather than in chromaffin cells during the sympathoadrenal development.

Renal interferon-inducible protein 16 expression is associated with disease activity and prognosis in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). However, the current management of LN remains unsatisfactory due to sneaky symptoms during early stages and lack of reliable predictors of disease progression. METHODS: Bioinformatics and machine learning algorithms were initially used to explore the potential biomarkers for LN development. Identified biomarker expression was evaluated by immunohistochemistry (IHC) and multiplex immunofluorescence (IF) in 104 LN patients, 12 diabetic kidney disease (DKD) patients, 12 minimal change disease (MCD) patients, 12 IgA nephropathy (IgAN) patients and 14 normal controls (NC). The association of biomarker expression with clinicopathologic indices and prognosis was analyzed. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were utilized to explore potential mechanisms. RESULTS: Interferon-inducible protein 16 (IFI16) was identified as a potential biomarker for LN. IFI16 was highly expressed in the kidneys of LN patients compared to those with MCD, DKD, IgAN or NC. IFI16 co-localized with certain renal and inflammatory cells. Glomerular IFI16 expression was correlated with pathological activity indices of LN, while tubulointerstitial IFI16 expression was correlated with pathological chronicity indices. Renal IFI16 expression was positively associated with systemic lupus erythematosus disease activity index (SLEDAI) and serum creatinine while negatively related to baseline eGFR and serum complement C3. Additionally, higher IFI16 expression was closely related to poorer prognosis of LN patients. GSEA and GSVA suggested that IFI16 expression was involved in adaptive immune-related processes of LN. CONCLUSION: Renal IFI16 expression is a potential biomarker for disease activity and clinical prognosis in LN patients. Renal IFI16 levels may be used to shed light on predicting the renal response and develop precise therapy for LN.

Trends and influencing factors of HIV health education receive rate among 0.57 million migrants in China from 2009 to 2017: a national population-based study.

INTRODUCTION: China has implemented Basic Public Health Service (BPHS) in 2009, aiming to improve the health status of the people, and the content of service includes implying health education for residents. As an important group of people, the migrants can easily become main reason for major infectious diseases such as HIV between different provinces, but the effect of receiving health education is still unknown for migrants. Therefore, the health education of China's migrant population has received widespread attention. METHODS: This study used the data of the China Migrants Dynamic Survey (CMDS) from 2009 to 2017, and evaluated the trend of HIV health education acceptance rate of different migrant groups across the country (n = 570,614). Logistic regression model was used to test the influencing factors of HIV health education rate. RESULTS: The study found that the overall HIV health education rate of Chinese migrants decreased from 2009 to 2017, and different types of migrants showed different trends. The proportion of migrants aged 20-35 who receive education fluctuates, and ethnic minorities, western regions, and migrants with high education were more likely to receive HIV health education. CONCLUSION: These findings identify when implementing health education for migrants, we can carry out more education for specific groups to promote the health equity of the migrant population.

Vaccination in the childhood and awareness of basic public health services program among internal migrants: a nationwide cross-sectional study.

BACKGROUND: Vaccination is proved to be one of the most effective and efficient way to prevent illness and reduce health inequality. Studies about association between vaccination inequalities in the childhood and awareness of basic public health services program among internal migrants in China are lacking. In this study, we aimed to explore the association between migrants' vaccination status between 0 and 6 years old and their awareness of the National Basic Public Health Services (BPHSs) project in China. METHODS: We included 10,013 respondents aged 15 years old or above of eight provinces from 2017 Migrant Population Dynamic Monitoring Survey in China, a nationwide cross-sectional study. Univariate and multivariable logistic regressions were used to assess vaccination inequalities and the awareness of public health information. RESULTS: Only 64.8% migrants were vaccinated in their childhood, which is far below the goal of national requirement of 100% vaccination. This also indicated the vaccination inequalities among migrants. Female, the middle-aged, married or having a relationship, the highly educated and the healthy population had higher awareness of this project than others. Both univariate and multivariate logistic regressions showed greatly significant association between vaccination status and some vaccines. Specifically, after adding convariates, the results showed that there were significant associations between the vaccination rates of eight recommended vaccines in the childhood and their awareness of BPHSs project (all p values < 0.001), including HepB vaccine (OR: 1.28; 95%CI: 1.19, 1.37), HepA vaccine (OR: 1.27; 95%CI: 1.15, 1.41), FIn vaccine (OR: 1.28; 95%CI: 1.16, 1.45), JE vaccine (OR: 1.14; 95%CI: 1.04, 1.27), TIG vaccine (OR: 1.27; 95%CI: 1.05, 1.47), DTaP vaccine (OR: 1.30; 95%CI: 1.11-1.53), MPSV vaccine (OR: 1.26; 95%CI: 1.07-1.49), HF vaccine (OR: 1.32; 95%CI: 1.11, 1.53), except for RaB vaccine (OR: 1.07; 95%CI: 0.89, 1.53). CONCLUSIONS: The vaccination inequalities exist among migrants. There is a strong relationship between the vaccination status in the childhood and the awareness rate of BPHSs project among migrants. From our findings we could know that the promotion of vaccination rates of the disadvantaged population such as the internal migrants or other minority population can help them increase the awareness of free public health services, which was proved to be beneficial for health equity and effectiveness and could promote public health in the future.

Renal C4d is a potential biomarker of disease activity and severity in pediatric lupus nephritis patients.

Background: Systemic lupus erythematosus (SLE), a multisystemic autoimmune disease, is very aggressive in pediatric-onset patients as they are prone to develop lupus nephritis (LN). Although renal C4d positivity is correlated with the activity of renal disease and SLE in adult-onset LN patients, available information for pediatric-onset patients is limited. Methods: To evaluate the potential diagnostic significance of renal C4d staining in pediatric LN patients, we retrospectively detected C4d staining by immunohistochemistry on renal biopsy specimens from 58 pediatric LN patients. The clinical and laboratory data at the time of the kidney biopsy and the renal disease activity of histological injury were analyzed according to the C4d staining status. Results: Glomerular C4d (G-C4d)-positive staining was detected in all 58 cases of LN. Patients with a G-C4d score of 2 displayed more severe proteinuria than those with a G-C4d score of 1 (24-h urinary protein: 3.40 ± 3.55 g vs. 1.36 ± 1.24 g, P < 0.05). Peritubular capillary C4d (PTC-C4d) positivity was found in 34 of 58 LN patients (58.62%). The PTC-C4d-positive patient groups (patients with a PTC-C4d score of 1 or 2) had higher serum creatinine and blood urea nitrogen levels as well as renal pathological activity index (AI) and SLE disease activity index (SLEDAI) scores; however, they had lower serum complement C3 and C4 levels compared to PTC-C4d-negative patients (P < 0.05). In addition, there was positive tubular basement membrane C4d (TBM-C4d) staining in 11 of 58 LN patients (18.96%), and a higher proportion of TBM-C4d-positive patients than TBM-C4d-negative patients (63.63% vs. 21.27%) had hypertension. Conclusion: Our study revealed that G-C4d, PTC-C4d, and TMB-C4d were positively correlated with proteinuria, disease activity and severity, and hypertension, respectively, in pediatric LN patients. These data suggest that renal C4d is a potential biomarker for disease activity and severity in pediatric LN patients, providing insights into the development of novel identification and therapeutic approaches for pediatric-onset SLE with LN.

Human iPSC-derived midbrain organoids functionally integrate into striatum circuits and restore motor function in a mouse model of Parkinson's disease.

Rationale: Parkinson's disease (PD) is a prevalent neurodegenerative disorder that is characterized by degeneration of dopaminergic neurons (DA) at the substantia nigra pas compacta (SNpc). Cell therapy has been proposed as a potential treatment option for PD, with the aim of replenishing the lost DA neurons and restoring motor function. Fetal ventral mesencephalon tissues (fVM) and stem cell-derived DA precursors cultured in 2-dimentional (2-D) culture conditions have shown promising therapeutic outcomes in animal models and clinical trials. Recently, human induced pluripotent stem cells (hiPSC)-derived human midbrain organoids (hMOs) cultured in 3-dimentional (3-D) culture conditions have emerged as a novel source of graft that combines the strengths of fVM tissues and 2-D DA cells. Methods: 3-D hMOs were induced from three distinct hiPSC lines. hMOs at various stages of differentiation were transplanted as tissue pieces into the striatum of naïve immunodeficient mouse brains, with the aim of identifying the most suitable stage of hMOs for cellular therapy. The hMOs at Day 15 were determined to be the most appropriate stage and were transplanted into a PD mouse model to assess cell survival, differentiation, and axonal innervation in vivo. Behavioral tests were conducted to evaluate functional restoration following hMO treatment and to compare the therapeutic effects between 2-D and 3-D cultures. Rabies virus were introduced to identify the host presynaptic input onto the transplanted cells. Results: hMOs showed a relatively homogeneous cell composition, mostly consisting of dopaminergic cells of midbrain lineage. Analysis conducted 12 weeks post-transplantation of day 15 hMOs revealed that 14.11% of the engrafted cells expressed TH+ and over 90% of these cells were co-labeled with GIRK2+, indicating the survival and maturation of A9 mDA neurons in the striatum of PD mice. Transplantation of hMOs led to a reversal of motor function and establishment of bidirectional connections with natural brain target regions, without any incidence of tumor formation or graft overgrowth. Conclusion: The findings of this study highlight the potential of hMOs as safe and efficacious donor graft sources for cell therapy to treat PD.

Effects of acupuncture on age-related macular degeneration: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In recent years, an increasing number of patients with age-related macular degeneration (AMD) have received acupuncture treatment, but there has been no systematic review to evaluate the effect of acupuncture on patients with AMD. PURPOSE: This meta-analysis aims to review the clinical efficacy of acupuncture in the treatment of AMD. METHODS: Randomized controlled trials up to September 4, 2022 were searched in the following databases: PubMed, Ovid Medline, Embase, Cochrane Library, The Chinese National Knowledge Infrastructure Database, VIP, Wanfang, and SINOMED. Two reviewers independently performed literature screening and data extraction. RevMan 5.4 was used for the meta-analysis. RESULTS: Nine of the 226 articles were finally included. A total of 508 AMD patients (631 eyes) were enrolled, including 360 dry eyes and 271 wet eyes. The results showed that acupuncture alone or as an adjunct therapy improved both the clinical efficacy and best-corrected visual acuity (BCVA) of AMD patients and reduced their central macular thickness. The certainty of the evidence ranged from "low" to "very low". CONCLUSION: There is no high-quality evidence that acupuncture is effective in treating patients with AMD; patients with dry AMD may benefit from acupuncture treatment. Considering the potential of acupuncture treatment for AMD, it is necessary to conduct a rigorously designed randomized controlled trials to verify its efficacy.

MicroRNAs of extracellular vesicles derived from mesenchymal stromal cells alleviate inflammation in dry eye disease by targeting the IRAK1/TAB2/NF-κB pathway.

PURPOSE: To investigate the efficacy and mechanisms of human umbilical cord-derived MSC-derived extracellular vesicles (hucMSC-EVs) in a mouse model of desiccation-induced dry eye disease (DED). METHODS: hucMSC-EVs were enriched by ultracentrifugation. The DED model was induced by desiccating environment combined with scopolamine administration. The DED mice were divided into the hucMSC-EVs group, fluorometholone (FML) group, PBS group, and blank control group. Tear secretion, corneal fluorescein staining, the cytokine profiles in tears and goblet cells, TUNEL-positive cell, and CD4+ cells were examined to assess therapeutic efficiency. The miRNAs in the hucMSC-EVs were sequenced, and the top 10 were used for miRNA enrichment analysis and annotation. The targeted DED-related signaling pathway was further verified by using RT‒qPCR and western blotting. RESULTS: Treatment with hucMSC-EVs increased the tear volume and maintained corneal integrity in DED mice. The cytokine profile in the tears of the hucMSC-EVs group presented with a lower level of proinflammatory cytokines than PBS group. Moreover, hucMSC-EVs treatment increased goblet cell density and inhibited cell apoptosis and CD4+ cell infiltration. Functional analysis of the top 10 miRNAs in hucMSC-EVs showed a high correlation with immunity. Among them, miR-125 b, let-7b, and miR-6873 were conserved between humans and mice and were associated with the IRAK1/TAB2/NF-κB pathway that was activated in DED. Furthermore, IRAK1/TAB2/NF-κB pathway activation and the abnormal expression of IL-4, IL-8, IL-10, IL-13, IL-17, and TNF-α were reversed by hucMSC-EVs. CONCLUSIONS: hucMSCs-EVs alleviate DED signs, suppress inflammation and restore homeostasis of the corneal surface by multitargeting the IRAK1/TAB2/NF-κB pathway via certain miRNAs.

[Evolution of auditory brainstem response in 0-6 years old normal hearing children and characteristics of children with abnormal acoustic conduction].

Objective:To explore the normal reference range of Click-ABR latency and interwave period in 0-6 years old children, and to analyze the clinical characteristics of Click-ABR in children with sound transmission function is abnormal. Methods:A total of 1791（3582 ears） normal hearing children aged 0-6 years and 176（258 ears） conductive hearing loss children were selected for Click-ABR. The differences of Click-ABR parameters in children of different months were analyzed, and the correlation between the degree of conductive hearing loss and Click-ABR parameters was explored. Results:The incubation period of wave Ⅰ was not correlated with the age of month, while the incubation period of wave Ⅲ, wave Ⅴ, waveⅠ-Ⅲ and wave Ⅰ-Ⅴ were highly correlated with the age of month. There was a positive correlation between the latency of wave Ⅰ and hearing threshold in the children with sound transmission function is abnormal under 80 dB nHL stimulation, and there was no difference between the standard values of wave Ⅰ-Ⅲ and Ⅰ-Ⅴ in the children with sound transmission function is abnormal and normal children. Conclusion:The latency of ABR wave Ⅲ and Ⅴ, and the interval between wave Ⅰ-Ⅲ and Ⅰ-Ⅴ shorten with the increase of age in children aged 0-6 years. The normal ABR values of children of different ages should be established in each hearing clinic for children as a reference. Combined with Click-ABR threshold and 80 dB nHL acoustic subwave Ⅰlatency, the abnormal conduction function can be preliminatively screened out, which should be further supplemented with other combinations of hearing diagnosis.

The impact of early-life antibiotics and probiotics on gut microbial ecology and infant health outcomes: a Pregnancy and Birth Cohort in Northwest China (PBCC) study protocol.

BACKGROUND: Unreasonable use of antibiotics and probiotics can alter the gut ecology, leading to antibiotic resistance and suboptimal health outcomes during early life. Our study aims are to clarify the association among antibiotic and probiotic exposure in early life, the microecology of the gut microbiota, and the development of antibiotic resistance; to investigate the long-term impact of antibiotics and probiotics on the health outcomes of infants and young children; and to provide a theoretical basis for the rational use of antibiotics and probiotics from a life course perspective. METHODS: The study is a prospective, longitudinal birth cohort study conducted in Shaanxi Province, China from 2018 to 2024. A total of 3,000 eligible mother-child pairs will be enrolled from rural, suburban, and urban areas. The recruitment of the participants begins at pregnancy, and the newborns will be followed up for 2 years at successive timepoints: within 3 days after birth, 42 days after birth, and at 3, 6, 12, 18, and 24 months of age. Sociodemographic data, environmental exposures, dietary patterns, psychological conditions, and medical and drug histories are collected. Cognitive and behavioural development among infants and young children and questionnaires on antibiotic knowledge and behaviour among caregivers will be collected at 12 and 24 months of age. The faecal samples are collected and analysed by 16S rRNA high-throughput sequencing and quantitative PCR (qPCR) for antibiotic resistance genes. DISCUSSION: The findings will inform antibiotic and probiotic use for pregnant women and infants and contribute to establishing rational use strategies of antibiotics and probiotics for paediatricians, health practitioners, and drug administration policy-makers. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Registry (ChiCTR) platform, http://www.chictr.org.cn (Record ID: ChiCTR2100047531, June 20, 2021).

Analgesic effect of epidural anesthesia via the intervertebral foramen approach in percutaneous transforaminal endoscopic discectomy: a retrospective study.

BACKGROUND: Satisfactory intraoperative analgesia is critical for percutaneous transforaminal endoscopic discectomy (PTED). Local anesthesia (LA) and epidural anesthesia (EA) are recommended for PTED. LA alone does not achieve satisfactory pain management during PTED and other analgesics or sedatives are usually needed. Traditional EA, which involves implanting an epidural catheter through the midline or paramedian, has disadvantages such as difficulty in catheterization and increased preoperative preparation time. Rather than performing conventional EA, we injected local anesthetics through the intervertebral foramen during the puncture process, which we termed lumbar transforaminal EA (LTEA), and observed its feasibility and safety. This study aimed to conduct a comprehensive comparison of differences in analgesia between LA and LTEA in patients with PTED. METHODS: We performed a retrospective analysis of patients who underwent PTED between January 2018 and January 2021. Patients were divided into LA and LTEA groups. Data obtained from the electronic medical records included primary outcomes (visual analog scale [VAS] scores and anesthesia satisfaction rate) and secondary outcomes, including vital signs such as heart rate (HR), mean arterial pressure (MAP), total dosage of fentanyl, operation time, X-ray exposure time, Oswestry Disability Index (ODI) scores, and complications. RESULTS: In total, 160 patients (80 in each group) were analyzed in this study. The VAS scores for lumbar and leg pain were significantly lower in the LTEA group than in the LA group (P < 0.0001). The anesthesia satisfaction rate was 90.0% in the LTEA group and 72.5% in the LA group (P < 0.005). MAP and HR values in the LTEA group were significantly lower than those in the LA group (P < 0.05). The total dose of fentanyl in the LTEA group was significantly lower than that in the LA group (P < 0.05). As for ODI values, the average operation time, X-ray exposure time, and incidence of complications were not significantly different between the two groups (P > 0.05). CONCLUSIONS: LTEA simplifies the process of EA and can achieve a good analgesic effect intraoperatively without increasing the preoperative preparation time; thus, it may be adopted as an alternative mode of anesthesia during PTED surgery.