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.

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.

Insights into the photocatalytic activation of peroxymonosulfate by visible light over BiOBr-cyclodextrin polymer complexes for efficient degradation of dye pollutants in water.

The combination of adsorption-photocatalysis and advanced oxidation processes (AOP) based on sulfate (SO4•-) for the treatment of organic pollution has the advantages of a high degradation rate, affordability, and an absence of secondary pollution. This study combined amphiphilic super-crosslinked porous cyclodextrin resin (PBCD-B-D), bismuth oxybromide (BiOBr), a composite material with dual functions of adsorption and photocatalysis, and AOP based on SO4•- for the treatment of Acid Orange 7 (AO7) in water. The combination of BiOBr/PBCD-B-D (BOP-24) with peroxymonosulfate (PMS) showed an optimal adsorption-photocatalytic effect. Compared to the 24% PBCD-B-D (BOP-24)/visible light system, the degradation efficiency of BOP-24/PMS system for AO7 is increased from 64.1% to 99.2% within shorter time (∼60 min). Moreover, the BOP-24/PMS system showed a wide range of pH application (pH = 3-11). The addition of Cl-, SO42-, and NO3- promoted the photodegradation of AO7, whereas the addition of CO32- did not. The free radical capture experiments of the BOP-24/PMS AO7 degradation system showed that •O2-, h+, •OH, and SO4•- are reactive species. The proposed BOP-24 system used adsorption and a unique cavity structure to enrich AO7 near the active site, thereby reducing the path for PMS activation. PMS also acted as an electron (e-) acceptor to promote the transfer of part of e- to PMS, thereby further improving the efficiency of carrier separation. The proposed system is an effective method to improve the degradation of pollutants and broadens the range of application of SO4•--based AOP technology.

Head circumference trajectories during the first two years of life and cognitive development, emotional, and behavior problems in adolescence: a cohort study.

The associations of early-life head circumference (HC) with child neurodevelopmental and mental health among generally healthy population remain unclear. We aimed to examine the associations of early-life HC trajectories with cognitive development and emotional and behavioral problems in adolescence and to identify the HC growth-sensitive period. We conducted a prospective, community-based birth cohort study in rural western China, and 745 adolescents aged 10-14 years were followed between June and December 2016. We assessed their HC eight times during the first 2 years of life and their adolescent cognitive, emotional, and behavioral outcomes using the Wechsler Intelligence Scale for Children-IV and Youth Self-Report-2001, respectively. We applied group-based trajectory modeling to identify the HC trajectories and conditional growth to derive the HC growth-sensitive periods. We identified five distinct HC trajectories characterized as Start below average-then decrease (7.8% of the sample), Start below average-then increase (6.8%), Start average-then decrease (33%), Consistently average (38%), and Consistently above average (14%). Infants in the trajectory of consistently above average had higher cognitive scores in adolescence compared to those from suboptimal trajectories, with adjusted mean differences ranging from 2.84 to 8.99 points. The conditional gains showed that the HC growth-sensitive period was between 0 and 18 months for child cognition. We found null associations between HC measures and adolescent emotional and behavioral problem scores. CONCLUSION: Early-life HC trajectories were associated with adolescent cognitive development. HC may serve as an inexpensive screening tool to monitor child development at risk during the first 18 months, particularly in resource-limited settings. WHAT IS KNOWN: • Postnatal head circumference (HC) has been shown to be associated with cognitive development in infants who were born premature and/or fetal growth restriction, while inconsistent associations were reported among generally healthy populations, especially in low- and middle- income countries, challenging its utility in public health practices. WHAT IS NEW: • Adolescents in the HC growth trajectory of consistently above average had higher cognitive scores compared to those with other suboptimal trajectories, while null findings were observed for adolescent emotional and behavioral health. • HC may serve as an inexpensive screening tool to monitor child development at risk during the first 18 months of life, particularly in resource-limited settings.

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.

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).

Sociodemographic disparities in the establishment of health records among 0.5 million migrants from 2014 to 2017 in China: a nationwide cross-sectional study.

BACKGROUND: Migrants account for a large part of China's population. Many policies and inventions have been taken to improve access to public health services and the health of migrants. China's Basic Public Health Services(BPHS) are a series of public health services in this policy domain, which aims at promoting the access of public health sevices and improve health equity of residents. The establishment of health records is the fundamental service of BPHS. However, there is little known about the establishment of health records among migrants in China, which hinders the more efficient provision of health services for migrants, and health equity is difficult to achieve. Based on the research gap, this study aims at showing the sociodemographic disparities in the establishment rate of health records, and identifying priorities and recommendations for promoting health equity of migrants in China. METHODS: This study used national data from China Migrants Dynamic Survey (CMDS) from 2014 to 2017 to evaluate the sociodemographic disparities in the establishment rate of health records and utilization of relevant public health services. The study included 539,926 respondents. Following the descriptive statistics of migrants, we showed the establishment rate of health records by sociodemographic characteristics and migrating related characteristics. Multivariate analysis was conducted to explore the associations between sociodemographic charicteristics, migrating related charicteristics and the establishment of health records. RESULTS: The establishment rate of health records among migrants in the sampled years were 22.99, 38.44, 27.29% respectively, and 29.18% in general, and there existed heterogeneity in the establishment rate of health records by sociodemographic charicteristics and migrating related charicteristics. Female migrants who were older, from middle age, married or living with partner, with higher educational attainment, with urban household registration, migrated for longer time, migrated for the reason of studying or family issues, migrated in province were more likely to establish health records. CONCLUSION: There existed sociodemographic disparities in the establishment rate of health records and inequalities in the utilization of health records services among migrants in China. Migrating related characteristics also had impact on the establishment status. Policies should take both supply side and demand side of health services to improve the health equity of migrants, which means that relative departments should continue to invest in primary healthcare centers to improve their ability to provide services as well as migrants' health literacy.

Thymocytes induce renal tubular epithelial cells to undergo the epithelial-to-mesenchymal transition.

BACKGROUND: Renal tubulointerstitial fibrosis is known to occur as a result of epithelial cell transformation into myofibroblasts via the epithelial-to-mesenchymal transition (EMT) process. It has been reported that macrophages, regulatory T (Treg) cells, and gamma delta T (γδ T) cells can promote fibrosis via EMT in vivo. OBJECTIVE: Our study intended to detect whether thymocytes can induce renal tubular cells to undergo the EMT. METHODS: Rat thymocytes were activated by phytohemagglutinin and concanavalin A. The rat renal tubular epithelial cells (NRK-52E) were incubated in a conditioned medium harvested from activated thymocytes or co-cultured with freshly isolated thymocytes for 48 hours. Real-time reverse transcription-polymerase chain reaction, immunofluorescence, and western blotting analysis were used to test the expression of the epithelial and mesenchymal markers in NRK-52E cells. Scratch assay was designed to test the cell migration abilities of NRK-52E cells. Student's t test and oneway analysis of variance test were used for statistical analysis. RESULTS: The combined stimulation with phytohemagglutinin and concanavalin A activated the primary isolated rat thymocytes. After treatment with conditioned medium or freshly isolated thymocytes, the expression levels of cytokeratin 19 and E-cadherin were downregulated in NRK-52E cells, while the mRNA and protein expression levels of alpha-smooth muscle actin, desmin, and vimentin were upregulated (P < 0.05). We found that the cell migration abilities of the induced NRK-52E cells were significantly improved. CONCLUSIONS: Both activated rat thymocytes (more percentage of CD8+ T cells) and freshly isolated thymocytes have promoting effects on the EMT of NRK-52E cells.

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.

Modulation of human induced neural stem cell-derived dopaminergic neurons by DREADD reveals therapeutic effects on a mouse model of Parkinson's disease.

BACKGROUND: Stem cell-based therapy is a promising strategy for treating Parkinson's disease (PD) characterized by the loss of dopaminergic neurons. Recently, induced neural stem cell-derived dopaminergic precursor cells (iNSC-DAPs) have been emerged as a promising candidate for PD cell therapy because of a lower tumor-formation ability. Designer receptors exclusively activated by designer drugs (DREADDs) are useful tools for examining functional synaptic connections with host neurons. METHODS: DREADD knock-in human iNSCs to express excitatory hM3Dq and inhibitory hM4Di receptors were engineered by CRISPR. The knock-in iNSCs were differentiated into midbrain dopaminergic precursor cells (DAPs) and transplanted into PD mice. The various behavior test such as the Apomorphine-induced rotation test, Cylinder test, Rotarod test, and Open field test were assessed at 4, 8, or 12 weeks post-transplantation with or without the administration of CNO. Electrophysiology were performed to assess the integrated condition and modulatory function to host neurons. RESULTS: DREADD expressing iNSCs were constructed with normal neural stem cells characteristics, proliferation ability, and differentiation potential into dopaminergic neuorns. DAPs derived from DREADD expressing iNSC showed matched function upon administration of clozapine N-oxide (CNO) in vitro. The results of electrophysiology and behavioral tests of transplanted PD mouse models revealed that the grafts established synaptic connections with downstream host neurons and exhibited excitatory or inhibitory modulation in response to CNO in vivo. CONCLUSION: iNSC-DAPs are a promising candidate for cell replacement therapy for Parkinson's disease. Remote DREADD-dependent activation of iNSC-DAP neurons significantly enhanced the beneficial effects on transplanted mice with Parkinson's disease.

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.

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.

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.

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.

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.

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.

An image reconstruction algorithm for electrical capacitance tomography based on robust principle component analysis.

Electrical capacitance tomography (ECT) attempts to reconstruct the permittivity distribution of the cross-section of measurement objects from the capacitance measurement data, in which reconstruction algorithms play a crucial role in real applications. Based on the robust principal component analysis (RPCA) method, a dynamic reconstruction model that utilizes the multiple measurement vectors is presented in this paper, in which the evolution process of a dynamic object is considered as a sequence of images with different temporal sparse deviations from a common background. An objective functional that simultaneously considers the temporal constraint and the spatial constraint is proposed, where the images are reconstructed by a batching pattern. An iteration scheme that integrates the advantages of the alternating direction iteration optimization (ADIO) method and the forward-backward splitting (FBS) technique is developed for solving the proposed objective functional. Numerical simulations are implemented to validate the feasibility of the proposed algorithm.

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.