Navigating therapeutic challenges in VEXAS syndrome: exploring IL-6 and JAK inhibitors at the forefront.

VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.

Correlation between Antibiotics-Resistance, Virulence Genes and Genotypes among Klebsiella pneumoniae Clinical Strains Isolated in Guangzhou, China.

Klebsiella pneumoniae is an important opportunistic pathogen causing community-acquired and hospital-acquired infections. This aim of this study was to analysis the antibiotic-resistance phenotypes, carbapenemase genes, virulence genes, and genotypes the 62 K. pneumoniae clinical isolates, and to explore the correlations between these isolates. The antimicrobial susceptibility profiles were determined using the BD Phoenix-100 system. Carbapenemase and virulence genes were detected using multiplex PCR. Out of the 62 K. pneumoniae clinical isolates, 79.0% were exhibited resistance to antibiotics, with 69.4% displaying multi-drug resistance. The rate of antibiotic-resistance was highest for penicillin (71.0%), followed by cephalosporins (66.1%), and lowest for carbapenems (29.0%). The detection rates of carbapenemase genes were as follows: KPC (56.5%), VIM (35.5%), and NDM (1.61%). Additionally, seven virulence genes were detected with the highest prevalence rates, of which entB and mrkD were at the top of the carrier rates with 95.2% each. The study classified 62 isolates into 13 clusters and 46 genotypes using ERIC-PCR. Cluster A6 exhibited the highest genetic diversity, comprising 20 strains and 13 genotypes. The statistical analysis revealed a strong correlation between MDR and resistance to penicillin and cephalosporin. Furthermore, genes related to siderophores were closely associated with mrkD. Genotypes identified by ERIC-PCR showed a negative correlation with allS. The study revealed a negative correlation between antibiotic resistance and genes kfu, ybtS, iutA, rmpA, and allS. Conversely, a positive correlation was observed between antibiotic resistance and genes entB and mrkD. The correlations identified in this study provide insights into the occurrence of hospital-acquired infections. The findings of this study may guide the prevention and control of K. pneumoniae outbreaks by utilizing appropriate medication.

The OsNAC24-OsNAP protein complex activates OsGBSSI and OsSBEI expression to fine-tune starch biosynthesis in rice endosperm.

Starch accounts for up to 90% of the dry weight of rice endosperm and is a key determinant of grain quality. Although starch biosynthesis enzymes have been comprehensively studied, transcriptional regulation of starch-synthesis enzyme-coding genes (SECGs) is largely unknown. In this study, we explored the role of a NAC transcription factor, OsNAC24, in regulating starch biosynthesis in rice. OsNAC24 is highly expressed in developing endosperm. The endosperm of osnac24 mutants is normal in appearance as is starch granule morphology, while total starch content, amylose content, chain length distribution of amylopectin and the physicochemical properties of the starch are changed. In addition, the expression of several SECGs was altered in osnac24 mutant plants. OsNAC24 is a transcriptional activator that targets the promoters of six SECGs; OsGBSSI, OsSBEI, OsAGPS2, OsSSI, OsSSIIIa and OsSSIVb. Since both the mRNA and protein abundances of OsGBSSI and OsSBEI were decreased in the mutants, OsNAC24 functions to regulate starch synthesis mainly through OsGBSSI and OsSBEI. Furthermore, OsNAC24 binds to the newly identified motifs TTGACAA, AGAAGA and ACAAGA as well as the core NAC-binding motif CACG. Another NAC family member, OsNAP, interacts with OsNAC24 and coactivates target gene expression. Loss-of-function of OsNAP led to altered expression in all tested SECGs and reduced the starch content. These results demonstrate that the OsNAC24-OsNAP complex plays key roles in fine-tuning starch synthesis in rice endosperm and further suggest that manipulating the OsNAC24-OsNAP complex regulatory network could be a potential strategy for breeding rice cultivars with improved cooking and eating quality.

Comparison of pulsed-field gel electrophoresis and a novel amplified intergenic locus polymorphism method for molecular typing of Campylobacter jejuni.

Campylobacter is regarded as the leading cause of zoonotic diseases and Campylobacter jejuni (C. jejuni) is one of the predominant pathogenic species. To track C. jejuni infections, various genotyping methods have been used. In this study, amplified intergenic locus polymorphism (AILP) was used to type C. jejuni for the first time. To confirm its feasibility, pulsed-field gel electrophoresis (PFGE) was performed as a control, and the results obtained by the AILP and PFGE methods were compared. Fifty-one isolates were resolved into 34 and 29 different genotypes with Simpson's indices of 0.976 and 0.967 using the AILP and PFGE methods, respectively. The adjusted Rand coefficient of the two approaches was as high as 0.845. In summary, the data showed that the two genotyping methods were similar for discriminating isolates and were both appropriate methods to distinguish whether two isolates were indistinguishable, but the AILP was faster and less costly than PFGE. Therefore, the AILP is a reliable, rapid, and highly discriminative method to genotype C. jejuni collected from poultry meat, which is helpful to effectively monitor C. jejuni.

Microwave ablation without subsequent lumpectomy versus breast-conserving surgery for early breast cancer: a propensity score matching study.

PURPOSE: To compare the efficacy of ultrasound-guided percutaneous microwave ablation (MWA) without subsequent lumpectomy and breast-conserving surgery (BCS) in patients with early breast cancer (BC). MATERIALS AND METHODS: This retrospective cohort study enrolled 106 patients with early BC (T0/1/2 N0/1 M0) treated by MWA (n = 21) or BCS (n = 85) from October 2014 to December 2020. Propensity score matching (PSM) was performed to balance the baseline characteristics between MWA and BCS groups. The tumor progression, overall survival (OS), disease-specific survival (DSS), complications, and cosmetic results were compared. RESULTS: After PSM, there were 21 patients with balanced baseline characteristics in each group. After a median follow-up of 43 months (range, 15-89 months), there was no significant difference in tumor progression (10% vs 2%, p = 0.18), OS (96% vs 99%, p = 0.36), DSS (100% vs 99%, p > 0.99), and complications (0% vs 19%, p = 0.58). The operation time of MWA was shorter (60 min vs 101 min, p < 0.001) than that of BCS. For the management of metastatic lymph nodes, five (5/21, 24%) patients with six metastatic nodes underwent ablation in the MWA group and three patients (3/21, 14%) with six metastatic nodes underwent axillary lymph node dissection in the BCS group. All the patients in the MWA group reported excellent cosmetic results, but 29% of BCS patients expressed dissatisfaction with breast asymmetry (10%) and scar formation (19%) (p < 0.001). CONCLUSION: This pilot study indicated that in selected early BC patients, microwave ablation without subsequent lumpectomy had comparable tumor control effect with breast-conserving surgery and better cosmetic results at an intermediate follow-up.HighlightsMWA without subsequent lumpectomy has a comparable interim survival effect and better cosmetic results as BCS in the treatment of selected early breast cancer.MWA has the potential to be a viable and promising therapeutic option for breast cancer patients reluctant or intolerant to surgery with the advantage of minimal invasion.

Rapid Genotyping of Campylobacter coli Strains from Poultry Meat by PFGE, Sau-PCR, and fla-DGGE.

The genotyping of Campylobacter coli was done using three methods, pulsed-field gel electrophoresis (PFGE), Sau-polymerase chain reaction (Sau-PCR), and denaturing gradient gel electrophoresis assay of flagellin gene (fla-DGGE) and the characteristics of these assays were compared. The results showed that a total of 53 strains of C. coli were isolated from chicken and duck samples in three markets. All isolates were clustered into 31, 33, and 15 different patterns with Simpson's index of diversity (SID) values of 0.972, 0.974, and 0.919, respectively. Sau-PCR assay was simpler, more rapid, and had higher discriminatory power than PFGE assay. Fla-DGGE assay could detect and illustrate the number of contamination types of C. jejuni and C. coli without cultivation, which saved more time and cost than Sau-PCR and PFGE assays. Therefore, Sau-PCR and fla-DGGE assays are both rapid, economical, and easy to perform, which have the potential to be promising and accessible for primary laboratories in genotyping C. coli strains.

Tanshinone IIA inhibits Leu27IGF-II-induced insulin-like growth factor receptor II signaling and myocardial apoptosis via estrogen receptor-mediated Akt activation.

Different stress condition stimulates the expression level of insulin-like growth factor receptor II (IGF-IIR) in cardiomyoblasts that lead to apoptosis. Tanshinone IIA (TSN), a pharmacologically active component from Danshen, has been shown cardioprotective effects against cardiac apoptosis induced by several stress conditions. Therefore, this study was conducted to assess the cardioprotective effects of TSN IIA mediated through the estrogen receptor (ER) in order to inhibit the Leu27IGF-II-enhanced IGF-IIR-mediated cardiac apoptosis. The estrogenic activity of TSN IIA was examined after myocardial cells were pretreated with the ER antagonist, and inhibited the phospho-inositide-3 kinase (PI3K). Here, we found that TSN IIA significantly induced ER that phosphorylated Akt. Further, Akt activation considerably suppressed the Leu27IGF-II induced IGF-IIR expression level and the downstream effectors, including Gαq and calcineurin as well as mitochondrial dependent apoptosis proteins including Bad, cytochrome c, and active caspase-3 that result in cardiac apoptosis resistance. However, the western blot analysis, JC-1 staining, and terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay revealed that TSN IIA attenuated Leu27IGF-II-induced IGF-IIR mediated cardiac apoptosis was reversed by an ER antagonist such as ICI 182780, and PI3K inhibition. All these findings demonstrate that TSN IIA exerts estrogenic activity, which can activate PI3K-Akt pathway, and thereby inhibits Leu27IGFII induced IGF-IIR mediated cardiac apoptosis. Thus, TSN IIA can be considered as an effective therapeutic strategy against IGF-IIR signaling cascade to suppress cardiac apoptosis.

Impact of COVID-19 on pediatric emergencies and hospitalizations in Singapore.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has impacted the provision of health services in all specialties. We aim to study the impact of COVID-19 on the utilization of pediatric hospital services including emergency department (ED) attendances, hospitalizations, diagnostic categories and resource utilization in Singapore. METHODS: We performed a retrospective review of ED attendances and hospital admissions among children < 18 years old from January 1st to August 8th 2020 in a major pediatric hospital in Singapore. Data were analyzed in the following time periods: Pre-lockdown (divided by the change in Disease Outbreak Response System Condition (DORSCON) level), during-lockdown and post-lockdown. We presented the data using proportions and percentage change in mean counts per day with the corresponding 95% confidence intervals (CIs). RESULTS: We attended to 58,367 children with a mean age of 5.1 years (standard deviation, SD 4.6). The mean ED attendance decreased by 331 children/day during lockdown compared to baseline (p < 0.001), attributed largely to a drop in respiratory (% change - 87.9, 95% CI - 89.3 to - 86.3, p < 0.001) and gastrointestinal infections (% change - 72.4, 95%CI - 75.9 to - 68.4, p < 0.001). Trauma-related diagnoses decreased at a slower rate across the same periods (% change - 40.0, 95%CI - 44.3 to - 35.3, p < 0.001). We saw 226 children with child abuse, with a greater proportion of total attendance seen post-lockdown (79, 0.6%) compared to baseline (36, 0.2%) (p < 0.001). In terms of ED resource utilization, there was a decrease in the overall mean number of procedures performed per day during the lockdown compared to baseline, driven largely by a reduction in blood investigations (% change - 73.9, 95%CI - 75.9 to - 71.7, p < 0.001). CONCLUSIONS: We highlighted a significant decrease in infection-related presentations likely attributed to the lockdown and showed that the relative proportion of trauma-related attendances increased. By describing the impact of COVID-19 on health services, we report important trends that may provide guidance when planning resources for future pandemics.

Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses.

Moringa oleifera Lam. (MO) is called the "Miracle Tree" because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta-analysis.

BACKGROUND: The present study focused on understanding the prognostic value of the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms rs1801133 (C667T) and rs1801131 (A1298C) in patients with colorectal cancer (CRC). METHODS: A systematic literature search was conducted in March 2016. Databases, including Medline, EMBASE, Cochrane and Chinese databases (including CNKI, Wanfang and VIP), were searched to identify the relevant articles describing MTHFR polymorphisms in patients with CRC. Data regarding overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were collected and analysed. RESULTS: Twenty-four studies with 5423 patients with CRC were included. Significant differences in OS, PFS and DFS were not observed among the different comparisons of patients carrying different alleles of the MTHFR rs1801133 polymorphism (including TT versus CC, TT versus CT + CC, CT + TT versus CC and CT versus CC). Compared with patients with the rs1801131 CA + AA genotypes, patients with the CC genotype had a shorter OS (hazard ratio = 1.85; 95% confidence interval = 1.30-2.65) and DFS (hazard ratio = 2.16; 95% confidence interval= 1.19-3.93). Significant differences in OS, PFS and DFS were not observed among the other patient groups (including CC versus AA, CC + CA versus AA and CA versus AA). Subgroup analysis of rs1801133 and rs1801131 showed that patients with CRC from Asian regions and Western regions demonstrated similar results. CONCLUSIONS: The MTHFR rs1801133 polymorphism was not associated with the prognosis of patients with CRC; however, rs1801131 may be associated with the prognosis of patients with CRC. Well-designed prospective studies are necessary to obtain a better understanding of the prognostic value of rs1801133 and rs1801131.

Molecular Detection and Genotyping of Toxoplasma gondii in Edward's Long-Tailed Rats (Leopoldamys edwardsi).

Toxoplasma gondii is an important zoonotic parasite infecting humans and various animals with a worldwide distribution. However, limited information is available on T. gondii infection in wild rats. The present study aimed to examine the prevalence and characterize the genotypes of T. gondii in wild rats in two regions of China. Brain tissues were collected from 111 Edward's long-tailed rats (Leopoldamys edwardsi) and 117 Bower's white-toothed rats (Berylmys bowersi) between November 2017 and January 2018. Genomic DNA was extracted and amplified by PCR targeting the T. gondii B1 gene. B1 gene-positive samples were genotyped at 10 genetic markers (SAG1, SAG2 [5', 3'] and [alternative], SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) using multilocus nested polymerase chain reaction/restriction fragment length polymorphism. Six (5.41%, 6/111) Edward's long-tailed rats from Chongqing Municipality were positive for T. gondii B1 gene, whereas no T. gondii infection was detected in Bower's white-toothed rats (n = 117) from Guangdong province. T. gondii prevalence in female and male rats was 1.77% (2/113) and 3.48 (4/115), respectively. Four of the six positive DNA samples were completely genotyped at 10 genetic loci and were identified as ToxoDB#20. The present study revealed the occurrence of T. gondii infection in Edward's long-tailed rats. These findings raised public health concerning about T. gondii infection in wild rats. These results provide reference data for understanding the distribution of T. gondii genotypes in wild rats in China.

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis.

BACKGROUND: Transforming growth factor-beta (TGF-ß) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-ß can be used as a prognostic indicator of colorectal cancer (CRC) remains controversial. METHODS: The Medline, EMBASE and Cochrane databases were searched from their inception to March 2016. The studies that focused on TGF-ß as a prognostic factor in patients with CRC were included in this analysis. Overall survival (OS) and disease-free survival (DFS) were analysed separately. A meta-analysis was performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. RESULTS: Twelve studies were included in the analysis, of which 8 were used for OS and 7 for DFS. In all, 1622 patients with CRC undergoing surgery were included. Combined HRs suggested that high expression of TGF-ß had a favourable impact on OS (HR = 1.68, 95% CI: 1.10-2.59) and DFS (HR = 1.11, 95% CI: 1.03-1.19) in CRC patients. For OS, the combined HRs of Asian studies and Western studies were 1.50 (95% CI: 0.61-3.68) and 1.80 (95% CI: 1.33-2.45), respectively. For DFS, the combined HRs of Asian studies and Western studies were 1.42 (95% CI: 0.61-3.31) and 1.11 (95% CI: 1.03-1.20), respectively. CONCLUSIONS: This meta-analysis demonstrates that TGF-ß can be used as a prognostic biomarker for CRC patients undergoing surgery, especially for CRC patients from Western countries.

Preventing intrahepatic infection after ablation of liver tumours in biliary-enteric anastomosis patients.

PURPOSE: To assess the value of bowel preparation plus targeted antibiotics for preventing intrahepatic infections after MWA of liver tumours in BEA patients. MATERIALS AND METHODS: This retrospective study included 21 patients (divided into two groups) with a history of BEA undergoing ultrasound-guided MWA of liver tumours from November 2008 to June 2014. Group A (n = 10) received single-antibiotic therapy (cefazedone 2 g bid 4, amoxicillin and flucloxacillin sodium 2 g bid 3, levofloxacin 0.5 g qd 3) after ablation, and group B (n = 11) received bowel preparation before ablation plus combined antibiotic therapy (imipenem and cilastatin sodium 1 g 1/12 h, linezolid 0.6 g 1/12 h). Patients were followed for 3 months. Incidences of fever, bacteraemia, and intrahepatic infections were compared, including the duration of fever and length of hospital stay. RESULTS: Following ablation, in group A, 90% of the patients (9/10) had fever, 60% (6/10) had bacteraemia, 60% (6/10) had liver abscess, and 10% (1/10) had biliary tract infection. In group B, no cases of bacteraemia or intrahepatic infection were reported, and the incidences of fever, bacteraemia, and liver abscess were substantially lower than group A (p = 0.002, 0.004, 0.004). Duration of fever and length of hospital stay were markedly shorter than group A (p = 0.002 0.003). CONCLUSIONS: Bowel preparation plus targeted antibiotic therapy can significantly reduce the incidences of fever, bacteraemia, and intrahepatic infections in BEA patients undergoing MWA of liver tumours. These preliminary results need to be further validated in randomised trials.

Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for the treatment of patients with adenomyosis and prior abdominal surgical scars: A retrospective study.

OBJECTIVE: The aim of this paper was to retrospectively compare the therapeutic efficacy and adverse effects of ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment for adenomyotic patients with or without prior abdominal surgical scars. METHODS: From January 2011 to March 2014, 534 patients with adenomyosis were referred for HIFU treatment. Among them, 118 patients had prior abdominal surgical scars, 416 patients did not have prior abdominal surgical scars. Contrast-enhanced MRI was used to evaluate the treatment outcomes. All the adverse effects were recorded. RESULTS: All patients completed USgHIFU treatment. A fractional ablation of 74.8 ± 27.8% was achieved in the group of patients without abdominal scars; the fractional ablation was 75.6 ± 22.3% in the group of patients with prior abdominal surgical scars. No significant difference in fractional ablation between the two groups was observed (p > 0.05). The rate of skin burn in the group of patients with prior abdominal surgical scars was significantly higher than that in the group without abdominal scars (2.5% vs. 0.2%, p < 0.05), but it is still acceptable. CONCLUSION: The prior abdominal surgical scars have no significant influence on the effectiveness of HIFU treatment for adenomyosis. The risk of skin burn is higher in patients with abdominal scars than without, but the incidence rate is still acceptable.

Evaluation of potential antidepressant-like activity of chalcone-1203 in various murine experimental depressant models.

Two classic animal behavior despair tests-the forced swimming test (FST) and the tail suspension test (TST) were used to evaluate antidepressant-like activity of a new chalcone compound, chalcone-1203 in mice. It was observed that chalcone-1203 at dose of 1, 5, and 10 mg/kg significantly reduced the immobility time in the FST and TST in mice 30 min after treatment. In addition, chalcone-1203 was found to exhibit significant oral activity in the FST in mice. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The main monoamine neurotransmitters and their metabolites in mouse brain regions were also simultaneously determined by HPLC-ECD. It was found that chalcone-1203 significantly increased the concentrations of the main neurotransmitters 5-HT and NE in the hippocampus, hypothalamus and cortex. Chalcone-1203 also significantly reduced the ratio of 5-HIAA/5-HT in the hippocampus and cortex, shown down 5-HT metabolism compared with mice treated with stress vehicle. In conclusion, chalcone-1203 produced significant antidepressant-like activity, and the mechanism of action may be due to increased 5-HT and NE in the mouse hippocampus and cortex.

Copper Deficiency Induces Oxidative Stress in Liver of Mice by Blocking the Nrf2 Pathway.

Copper (Cu) is an essential metal required for many physiological processes and biological reactions. Liver is the main organ of metabolism of Cu and is also the site where synthesis of some metalloproteins. The purpose of this study is to explore the effects of Cu deficiency on the liver and to evaluate the changes in liver oxidative stress levels to reveal its possible impact mechanisms. Mice were feed to a nutritional Cu-deficiency diet from weaning and injected with copper sulfate (CuSO4) intraperitoneally to correct Cu deficiency. Cu deficiency resulted in reduced liver index, liver histological alteration, and oxidative stress; decreased the contents of Cu and ALB; elevated ALT and AST concentrations in serum together with decreased mRNA and protein expressions of Nrf2 pathway related molecules (Nrf2, HO-1, NQO1); and increased mRNA and protein expressions of Keap1. However, the supplement of copper sulfate (CuSO4) significantly ameliorated the changes mentioned above. Our results indicate that Cu deficiency can cause hepatic damage in mice is associated with the activation of oxidative stress and inhibition of Nrf2 pathway.

Emerging biologic frontiers for Sjogren's syndrome: Unveiling novel approaches with emphasis on extra glandular pathology.

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral EBNA-1 and BamHI-W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression-free survival (PFS) was significantly longer in EBNA-1 high or BamHI-W high groups. A longer PFS was also observed in patients with both high plasma EBNA-1 or BamHI-W and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA-1 and BamHI-W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

[The application of network scale-up method on female sex workers and clients size estimation in Taizhou city].

OBJECTIVE: To estimate the size of female sex workers and clients in Taizhou city. METHODS: A household survey using network scale-up method (NSUM) was conducted among the 3000 community residents in Taizhou city from August to October in 2011, which aimed to estimate the social network size (c value) of Taizhou residents, and the c value was adjusted by demographic characteristics, back estimation and outlier elimination. Using the adjusted c value, the number of acquaintance of female sex workers or clients and the respect level toward female sex workers or clients were used to estimate the size of female sex workers and clients. RESULTS: A total of 2783 valid questionnaires were collected, among which 1380 (49.6%) were collected from Taixing city, 1403 (50.4%) were collected from Jingjiang city. 1334 respondents were male (47.9%) and 1449 (47.9%) respondents were female. The mean age was (39.4 ± 10.7) years. The average personal social network size using original data for Taizhou residents was 525, which differed from place, sex, age, educational level and marriage status. Using the remaining known populations through back estimation, the social network size was 419 and became 424 after the elimination of outliers. The estimated population size for female sex worker was 6370 (95%CI: 5886 - 6853), which accounted for 0.52% (6370/1 229 980) of the total number of female aged from 15 to 49. The estimated population size for clients was 15 202 (95%CI: 14 560 - 15 847), which accounted for 1.28% (15 202/1 190 340) of the total number of males aged from 15 to 49 and the ration of clients to female sex worker was 2.39:1. CONCLUSION: NSUM is an easy and quick way to estimate the size of female sex workers or clients, but the estimated sizes are subject to bias and error due to estimate effect and sample representativeness.

Application of artificial intelligence for automatic cataract staging based on anterior segment images: comparing automatic segmentation approaches to manual segmentation.

Purpose: Cataract is one of the leading causes of blindness worldwide, accounting for >50% of cases of blindness in low- and middle-income countries. In this study, two artificial intelligence (AI) diagnosis platforms are proposed for cortical cataract staging to achieve a precise diagnosis. Methods: A total of 647 high quality anterior segment images, which included the four stages of cataracts, were collected into the dataset. They were divided randomly into a training set and a test set using a stratified random-allocation technique at a ratio of 8:2. Then, after automatic or manual segmentation of the lens area of the cataract, the deep transform-learning (DTL) features extraction, PCA dimensionality reduction, multi-features fusion, fusion features selection, and classification models establishment, the automatic and manual segmentation DTL platforms were developed. Finally, the accuracy, confusion matrix, and area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the performance of the two platforms. Results: In the automatic segmentation DTL platform, the accuracy of the model in the training and test sets was 94.59 and 84.50%, respectively. In the manual segmentation DTL platform, the accuracy of the model in the training and test sets was 97.48 and 90.00%, respectively. In the test set, the micro and macro average AUCs of the two platforms reached >95% and the AUC for each classification was >90%. The results of a confusion matrix showed that all stages, except for mature, had a high recognition rate. Conclusion: Two AI diagnosis platforms were proposed for cortical cataract staging. The resulting automatic segmentation platform can stage cataracts more quickly, whereas the resulting manual segmentation platform can stage cataracts more accurately.