N6-methyladenosine methylation regulator RBM15 promotes the progression of diabetic nephropathy by regulating cell proliferation, inflammation, oxidative stress, and pyroptosis through activating the AGE-RAGE pathway.

BACKGROUND: Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world, and m6A modification plays a critical role in the progression of DN. We aimed to find m6A-related genes and their regulatory mechanisms in DN. METHODS: The expression levels of four important m6A-related genes (METTL16, RBM15, IGF2BP1, and ALKBH5) were detected by quantitative real-time PCR (RT-qPCR). RBM15 was chosen and its function was explored. The downstream pathway of RBM15 was screened by transcriptome sequencing. The levels of AGE, inflammation, and oxidative stress were determined with enzyme-linked immunosorbent assay, and the expression of AGE-RAGE pathway-related proteins were detected by Western blot (WB). Cell proliferation was assessed by Cell counting Kit-8 (CCK-8). The levels of pyroptosis-related proteins were evaluated by RT-qPCR or WB. RESULTS: METTL16 and RBM15 were up regulated in the mouse model of DN, in which RBM15 was more significant. Silencing RBM15 recovered cell proliferation, reduced the levels of inflammation factors, and inhibited cell pyroptosis in high glucose-induced HK-2 cells. Transcriptome sequencing suggested that the AGE-RAGE pathway might be downstream of RBM15. RBM15 knockdown reduced AGE level and the expression of AGE-RAGE pathway-related proteins. After silencing RBM15, we found that activating the AGE-RAGE pathway inhibited cell proliferation, increased the levels of inflammation factors, promoted oxidative stress, and induced cell pyroptosis in HK-2 cell model of DN. CONCLUSION: The m6A-related gene RBM15 inhibited cell proliferation, promoted inflammation, oxidative stress, and cell pyroptosis, thereby facilitating the progression of DN through the activation of the AGE-RAGE pathway.

[Intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length in 16 887 neonates with a gestational age of 27-42 weeks in Shenzhen, China].

OBJECTIVE: To establish the intrauterine growth curves of neonates in Shenzhen, China and to investigate the intrauterine growth of neonates in Shenzhen. METHODS: Cross-sectional cluster sampling was performed for an on-the-spot investigation of 16 887 neonates (9 418 males and 7 469 females) with a gestational age of 27-42 weeks who were born in two hospitals in Shenzhen from April 2013 to September 2015. The Lambda Mu Sigma (LMS) method was used for the curve fitting of body weight, body length, head circumference, chest circumference, and crown-rump length. RESULTS: The 3rd-97th percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length were plotted for the neonates with a gestational age of 27-42 weeks who were divided into three groups (male, female, and mixed). The male neonates had significantly higher curves for the five indices than the female counterparts. The pattern and changing trend of body weight curves of these neonates were basically consistent with those in China Neonatal Network. CONCLUSIONS: The percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length in neonates with a gestational age of 27-42 weeks in Shenzhen which has been established can provide a reference for clinical practice in the department of neonatology.

Sensitivity of the Standard Chlamydia trachomatis Culture Method Is Improved After One Additional In Vitro Passage.

BACKGROUND: Chlamydia trachomatis causes the most common bacterial sexually transmitted infection (STI) worldwide. Although highly sensitive nucleic acid amplification tests (NAATs) are used to routinely diagnose chlamydial infection, C. trachomatis isolation by cell culture is still preferred for legal cases and epidemiological studies because of its high specificity; however, the sensitivity of traditional two-passage diagnostic cultures is significantly lower than that of NAATs. Therefore, we sought to analyze if additional in vitro passaging of clinical samples would improve detection sensitivity of C. trachomatis. METHODS: Clinical swabs (n = 428) were collected from Tianjin Medical University General Hospital, grown in McCoy cells for up to five passages, and analyzed for the presence of inclusions by iodine staining. Results were confirmed by routine PCR-based methods. RESULTS: Viable C. trachomatis organisms were detected in 91 (21.26%) swabs with the traditional two-passage protocol, which increased to 145 (33.88%) and 149 (34.81%) following three and four passages, respectively. Thus, the standard protocol yielded a false-negative rate of nearly 39%. Subsequent PCR-based diagnostics revealed a concordance rate of 80.98% between these two methods without any false negatives. CONCLUSION: The results of this study support the use of a three-passage Chlamydia culture procedure to increase the detection sensitivity of this method.

[Study on height-weight indices in newborns of different gestational ages].

OBJECTIVE: To establish height-weight indices in newborns of different gestational ages and to provide reference data for evaluation of intrauterine fetal growth. METHODS: The weight, height, crown-rump length, head circumference, and chest circumference of 8 357 newborns were measured in Maternal and Child Health Care Hospital of Bao'an District of shenzhen between 2005 and 2006, with the method of fact-finding investigation with cross-sectional cluster sampling, to establish the height-weight indices in newborns of different gestational ages. RESULTS: Five gender-specific height-weight indices (Quetelet Index, QI; Kaup Index, KI; Rohrer Index, RI; Livi Index, LI; Polock Index, PI) in newborns of different gestational ages (28-44 weeks of gestation) in three different groups (boys+girls, boys, and girls) were established in Shenzhen, China, and were expressed as mean gestational weeks±SD. The five indices above all increased with increasing gestational age, and the highest values appeared at 41-43 gestational weeks, suggesting that body density and enrichment degree increased constantly with increasing gestational age. Three indices (QI, KI and PI) were higher in boys than in girls (P<0.05). CONCLUSIONS: With the increasing gestational age, the body density and enrichment degree of newborns increase, and the enrichment degree in boys is better than that in girls.

The volumetric ADC histogram analysis in differentiating stage IA endometrial carcinoma from endometrial polyp.

OBJECTIVE: This study aimed to explore the value of apparent diffusion coefficient (ADC) histogram based on whole lesion volume in distinguishing stage IA endometrial carcinoma from the endometrial polyp. METHODS: MRI of 108 patients with endometrial lesions confirmed by pathology were retrospectively analysed, including 65 cases of stage IA endometrial carcinoma and 43 cases of endometrial polyp. The volumetric ADC histogram metrics and general imaging features were evaluated and measured simultaneously. All the features were compared between the 2 groups. The receiver operating characteristic curve was utilized to evaluate the diagnostic performance. RESULTS: The mean, max, min, and percentiles (10th, 25th, 50th, 75th, 95th) ADC values of endometrial carcinoma were significantly lower than that of polyp (all P < .05). The skewness and kurtosis of ADC values in the endometrial carcinoma group were significantly higher than those in the endometrial polyp group, and the variance of ADC values in the endometrial carcinoma group was lower than those in the endometrial polyp group (all P < .05). Endometrial carcinoma demonstrated more obvious myometrial invasion combined with intralesion haemorrhage than polyp (all P < .05). The 25th percentile of ADC values achieved the largest areas under the curve (0.861) among all the ADC histogram metrics and general imaging features, and the sensitivity and specificity were 83.08% and 76.74%, with the cut-off value of 1.01 × 10-3 mm2/s. CONCLUSION: The volumetric ADC histogram analysis was an effective method in differentiating endometrial carcinoma from an endometrial polyp. The 25th percentile of ADC values has satisfactory performance for detecting malignancy in the endometrium. ADVANCES IN KNOWLEDGE: The ADC histogram metric based on whole lesion is a promising imaging-maker in differentiating endometrial benign and malignant lesions.

Antibiotic Resistance Profiles and MLST Typing of Staphylococcus Aureus Clone Associated with Skin and Soft Tissue Infections in a Hospital of China.

Objective: To analyze the antibiotic resistance profile, virulence genes, and molecular typing of Staphylococcus aureus (S. aureus) strains isolated in skin and soft tissue infections at the First Affiliated Hospital, Gannan Medical University, to better understand the molecular epidemiological characteristics of S. aureus. Methods: In 2023, 65 S. aureus strains were isolated from patients with skin and soft tissue infections. Strain identification and susceptibility tests were performed using VITEK 2 and gram-positive bacteria identification cards. DNA was extracted using a DNA extraction kit, and all genes were amplified using polymerase chain reaction. Multilocus sequence typing (MLST) was used for molecular typing. Results: In this study, of the 65 S. aureus strains were tested for their susceptibility to 16 antibiotics, the highest resistance rate to penicillin G was 95.4%. None of the staphylococcal isolates showed resistance to ceftaroline, daptomycin, linezolid, tigecycline, teicoplanin, or vancomycin. fnbA was the most prevalent virulence gene (100%) in S. aureus strains isolated in skin and soft tissue infections, followed by arcA (98.5%). Statistical analyses showed that the resistance rates of methicillin-resistant S. aureus isolates to various antibiotics were significantly higher than those of methicillin-susceptible S. aureus isolates. Fifty sequence types (STs), including 44 new ones, were identified by MLST. Conclusion: In this study, the high resistance rate to penicillin G and the high carrying rate of virulence gene fnbA and arcA of S.aureus were determine, and 44 new STs were identified, which may be associated with the geographical location of southern Jiangxi and local trends in antibiotic use. The study of the clonal lineage and evolutionary relationships of S. aureus in these regions may help in understanding the molecular epidemiology and provide the experimental basis for pathogenic bacteria prevention and treatment.

Eccrine porocarcinoma in the tempus of an elderly woman: A case report.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin tumor that mainly affects the elderly population. Tumors often present with slow growth and a good prognosis. EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry. However, surgical management alone may be inadequate if the tumor has metastasized. However, currently, surgical resection is the most commonly used treatment modality. CASE SUMMARY: A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area, with no obvious itching or pain, for more than four months. Histopathological examination showed small columnar and short spindle-shaped cells; thus, basal cell carcinoma was suspected. However, immunohistochemical analysis revealed the expression of cytokeratin 5/6, p63 protein, p16 protein, and Ki-67 antigen (40%), and EPC was taken into consideration. The skin biopsy was repeated, and hematoxylin and eosin staining revealed ductal differentiation in some cells. Finally, the patient was diagnosed with EPC, and Mohs micrographic surgery was performed. We adapted follow-up visits in a year and not found any recurrence of nodules. CONCLUSION: This case report emphasizes the diagnosis and differentiation of EPC.

Modified extended object tracker for 2D lidar data using random matrix model.

The random matrix (RM) model is a typical extended object-modeling method that has been widely used in extended object tracking. However, existing RM-based filters usually assume that the measurements follow a Gaussian distribution, which may lead to a decrease in accuracy when the filter is applied to the lidar system. In this paper, a new observation model used to modify an RM smoother by considering the characteristics of 2D LiDAR data is proposed. Simulation results show that the proposed method achieves a better performance than the original RM tracker in a 2D lidar system.

Pelvic floor parameters predict postpartum stress urinary incontinence: a prospective MRI study.

OBJECTIVE: To investigate the pelvic floor changes in primiparas with postpartum stress urinary incontinence (SUI) after vaginal delivery using pelvic floor MRI. MATERIALS AND METHODS: Fifty-two women were enrolled in the primiparous stress urinary incontinent (PSUI) group and 51 in the primiparous continent (PC) group. Thirty nulliparas were also recruited as the nulliparous control (NC) group. Levator ani muscle (LAM) injury, levator hiatus area (LHA), H-line, M-line, the distance from the bladder neck and cervix to the pubococcygeal line (B-PCL and U-PCL), levator plate angle, the anterior angle of the urethra, bladder neck descent, retrovesicourethral angle, functional urethral length, and a bladder neck funnel were evaluated on MRI images. Univariate and multivariate logistic regression analyses were used to explore anatomical predictors for SUI. RESULTS: The primiparas in the PSUI group showed more obvious LAM injuries than in the PC groups (p = 0.001). LAM function assessment: the PSUI group had larger LHA and shorter B-PCL and U-PCL than the other groups during straining. Assessment of urethral mobility and function: the PSUI group had larger anterior angle of the urethra, bladder neck descent, retrovesicourethral angle, and shorter functional urethral length than the other two groups (all p < 0.05). Up to 88.5% of primiparas in the PSUI group showed bladder funnel (p < 0.001). The logistic regression analysis showed that retrovesicourethral angle, functional urethral length, and the presence of bladder funnel were significantly associated with postpartum SUI (p < 0.05). CONCLUSIONS: Increased retrovesicourethral angle, shortened functional urethral length, and the presence of bladder funnel may be anatomical predictors for SUI in the early postpartum period. Urethral sphincter dysfunction plays an essential role in developing postpartum SUI. CRITICAL RELEVANCE STATEMENT: This study used several measurements to reflect the anatomical structure and functional changes of the pelvic floor to identify the best anatomical predictors associated with postpartum stress urinary incontinence (SUI), aiming to provide new insights into treatment strategies for postpartum SUI. KEY POINTS: • Increased retrovesicourethral angle, shortened functional urethral length, and the presence of bladder funnel are more commonly seen in primiparas with SUI. • The combination of retrovesicourethral angle, functional urethral length, and bladder funnel had the highest diagnostic performance in predicting postpartum SUI (AUC=0.947). • Urethral sphincter dysfunction may be the main pathophysiological foundation in SUI development.

Associated Outcomes of Different Intravenous Antibiotics Combined with 2% Mupirocin Ointment in the Treatment of Pediatric Patients with Staphylococcal Scalded Skin Syndrome.

Purpose: To compare treatment duration, influencing factors, and costs among intravenous antibiotic groups combined with 2% mupirocin ointment for treating staphylococcal scalded skin syndrome (SSSS). Patients and Methods: Sex, age, onset days before admission, febrile status, white blood cell (WBC) count, and C-reactive protein (CRP) level were recorded as baseline characteristics for 253 included patients. The antibiotic sensitivity results were statistically compared by Cochran's Q test. Kruskal-Wallis tests were used to compare days and the total costs of hospitalization with different intravenous antibiotic applications. Mann-Whitney U-tests or Spearman's rank correlation tests were used for the univariate analysis. Finally, a multivariate linear regression model was employed to determine the variables with statistical significance. Results: The sensitivity rates of oxacillin (84.62%), vancomycin (100%), and mupirocin (100%) were significantly higher than those of clindamycin (7.69%) (p<0.0001). The duration of intravenous ceftriaxone administration was significantly longer than that of amoxicillin-clavulanic acid, cefathiamidine, and cefuroxime (p<0.01). The total hospitalization costs for cefathiamidine were significantly higher than those for amoxicillin-clavulanic acid and cefuroxime (p<0.05). According to the multiple linear regression, ages ≥60 months old were correlated with shorter treatment duration (ß=-1.48, [95% CI: -2.29, -0.66] for amoxicillin-clavulanic acid, and ß=-1.44, [95% CI: -2.06, -0.83] for cefathiamidine, and ß=-0.96, [95% CI: -1.58, -0.34] for cefuroxime) (all p<0.01). In multivariate analysis for cefathiamidine, higher WBC count (ß=0.05, [95% CI: 0.01, 0.10], p<0.05) and CRP level (ß=1.12, [95% CI: 0.14, 2.10], p<0.05) were associated with longer treatment course. Conclusion: Oxacillin resistance was rare, and clindamycin resistance was high in pediatric patients with SSSS in our district. Intravenous amoxicillin-clavulanic acid and cefuroxime combined with topical mupirocin were favorable due to a shorter intravenous treatment course and lower costs. Younger age, elevated WBC count, and CRP levels could indicate a longer course of treatment with intravenous antibiotics.

Changes of Gut Microbiome in Adolescent Patients with Chronic Spontaneous Urticaria After Omalizumab Treatment.

Purpose: Omalizumab is a humanized anti-immunoglobulin (Ig) E monoclonal antibody that is effective in treating some patients with chronic spontaneous urticaria (CSU) who do not respond to antihistamines. Gut microbiome plays a role in the pathogenesis of allergies and autoimmune diseases. Here, we investigated differences in the gut microbiome of adolescent CSU patients before and after omalizumab treatment, which has not been previously reported. Patients and Methods: Ten adolescent CSU patients were given 300 mg omalizumab subcutaneously in three treatments at 4-week intervals. Urticaria Activity Score (UAS7) was applied to evaluate the efficacy of each omalizumab treatment during follow-up. Fecal samples were collected before and 12 weeks after the first treatment. Total DNA of the gut microbiota in all fecal samples were extracted. The 16S rRNA gene-targeted sequencing technology was used for the analysis of the diversity and distribution of gut microbiome, followed by bioinformatics analysis. Results: UAS7 scores decreased significantly after each treatment compared with the baseline (all P < 0.0001). There were five well-controlled responders and five non-responders after three treatment sessions of omalizumab. The dominant bacteria phyla in all fecal samples were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Alpha diversity analysis showed no significant difference before and after treatment (P > 0.05), whereas beta diversity analysis revealed a significant difference in the bacterial abundance before and after treatment (P < 0.01). The relative abundance of Alphaproteobacteria and Betaproteobacteria at the class level and Burkholderia, Rhodococcus, and Sphingomonas at the genus level decreased significantly after treatment (linear discriminant analysis > 4, P < 0.05). The functional prediction results showed that the dioxin and xylene degradation pathways were more abundant before treatment. Conclusion: Omalizumab is effective in treating CSU and the abundance of Alphaproteobacteria and Betaproteobacteria was reduced after treatment, which may help improve the treatment outcomes in adolescent CSU patients.

The Effect of Amoxicillin Pre-Exposure on Treatment Outcomes and Antimicrobial Susceptibility in Patients with Urogenital Chlamydia trachomatis Infection.

Purpose: We investigated the influence of amoxicillin pre-exposure on treatment outcomes, Chlamydia trachomatis (CT) culture, the presence of drug-resistant genes, minimum inhibitory concentrations (MICs), and fractional inhibitory concentrations (FICs) in CT clinical strains. Additionally, we explored the effect of different antimicrobial combinations on CT. Patients and Methods: Clinical data of 62 patients with CT infection were recorded. Of these, 33 had pre-exposure to amoxicillin and 29 did not. Among patients with pre-exposure, 17 received azithromycin and 16 received minocycline. Among the patients without pre-exposure, 15 received azithromycin and 14 received minocycline. All patients underwent microbiological cure follow-ups one month after completing the treatment. 23S rRNA gene mutations, acquisition of tet(M) and tet(C) were detected using reverse transcription PCR (RT-PCR) and PCR, respectively. The MICs and FICs of azithromycin, minocycline, and moxifloxacin, alone or in combination, were determined using the microdilution and checkerboard methods, respectively. Results: More cases of treatment failure occurred in pre-exposed patients, in both treatment groups (P <0.05). No 23S rRNA gene mutations or tet(M) and tet(C) acquisitions were found. More inclusion bodies were cultured from patients without amoxicillin pre-exposure than from those with pre-exposure (P <0.0001). The MICs of all antibiotics were higher in pre-exposed patients than in those without pre-exposure (P <0.01). The FICs of azithromycin plus moxifloxacin were lower than those of the other antibiotic combinations (P <0.0001). The synergy rate of azithromycin plus moxifloxacin was significantly higher than those of azithromycin plus minocycline and minocycline plus moxifloxacin (P <0.001). The FICs of all antibiotic combinations were comparable between isolates from the two patient groups (all P >0.05). Conclusion: Pre-exposure to amoxicillin in CT patients may inhibit CT growth and decrease sensitivity of CT strains to antibiotics. Azithromycin plus moxifloxacin may be a promising treatment regimen for genital CT infections with treatment failure.

Solitary Interdigital Condyloma Latum in a Female Adolescent: A Case Report of an Unusual Form of Secondary Syphilis.

Condylomata lata are flat-topped, moist papules or plaques usually found in the anogenital area as cutaneous manifestations of secondary syphilis. Here, we present a unique case of a solitary interdigital condyloma latum of secondary syphilis in a 16-year-old female sex worker without other cutaneous findings. Sexual contact history, histopathology, including direct detection of Treponema pallidum, and serological tests were essential for the diagnosis of this case. The patient reached serological cure with two doses of intramuscularly delivered penicillin G benzathine. Owing to the dramatic rise in the incidence of primary and secondary syphilis, medical workers should be aware of the atypical skin manifestations of secondary syphilis in adolescents who are at risk of acquiring sexually transmitted diseases to avoid the progression to late syphilis and further transmission to sexual partners.

Cognitive-adaptive Functioning Gap and Mediating Factors that Impact Adaptive Functioning in Chinese Preschool-aged Children with Autism Spectrum Disorder.

This study aimed to investigate the gap between adaptive functioning and cognitive functioning, especially verbal and nonverbal intelligence quotient (IQ) in Chinese children with ASD. We systematically explored cognitive functioning, ASD severity, early signs of developmental abnormalities, and socioeconomic factors as mediating factors of adaptive functioning. We enrolled 151 children (age: 2.5?6 years) with ASD and categorized them into one group with IQ ≥ 70 and another with IQ < 70. The two groups were calibrated for age, age at diagnosis, and IQ, and the relationship of adaptive skills with vocabulary acquisition index (VAI) and nonverbal index (NVI) were separately analyzed. Results show that the gap between IQ and adaptive functioning was significant in children with ASD having IQ ≥ 70, with both VAI and NVI showing statistically significant differences (all P < 0.001). VAI correlated positively with scores for overall adaptive skills and specific domains, whereas NVI had no significant correlations with adaptive skill scores. Age of first walking unaided had an independent positive correlation (all P < 0.05) with scores of adaptive skills and specific domains. IQ-adaptive functioning gap is significant in children with ASD having IQ ≥ 70, suggesting that defining "high-functioning autism" merely on the basis of IQ is not appropriate. Verbal IQ and early signs of motor development are specific and possible predictors of adaptive functioning in children with ASD, respectively.

Stereotactic radiosurgery for orbital cavernous hemangiomas.

OBJECTIVE: The goal of this study was to assess the safety and efficacy of single-session Gamma Knife radiosurgery (GKRS) for orbital cavernous hemangiomas (OCHs). METHODS: Patients who presented with an OCH between September 1999 and May 2022 and were treated with single-session GKRS were included in this single-center cohort study. RESULTS: There were 23 patients (7 males and 16 females) in this study. The median margin dose was 12 Gy (range 11-13 Gy). The median clinical and radiological follow-ups were 45 months (range 5-190 months) and 45 months (range 6-190 months), respectively. Nine (69.2%) of 13 patients with visual acuity impairment had improvement in best corrected visual acuity. Of the 8 patients with visual field defects, 5 patients (62.5%) had complete resolution. Tumor regression was observed in 22 patients (95.7%). The mean relative reduction in tumor volume was 82.6% ± 23.7%. The relative reductions in tumor volume were 33%, 49%, 72%, 84%, and 89% at 6, 12, 24, 36, and 48 months, respectively. Adverse effects of radiation were not observed. CONCLUSIONS: GKRS appears to be safe and efficacious for treating OCHs over long-term follow-up. The treatment is associated with a high rate of regression in OCHs and remarkable improvement in both visual acuity and visual field deficits.

Thiazolidione derivatives targeting the histidine kinase YycG are effective against both planktonic and biofilm-associated Staphylococcus epidermidis.

AIM: To evaluate the efficacies of six derivatives of Compound 2, a novel YycG histidine kinase inhibitor with the thiazolidione core structure in the treatment of medical device-related biofilm infections. METHODS: The minimal inhibitory concentration (MIC) of the derivatives was determined using the macrodilution broth method, and the minimal bactericidal concentration (MBC) was obtained via sub-culturing 100 µL from each negative tube from the MIC assay onto drug-free Mueller-Hinton agar plates. Biofilm-killing effect for immature (6 h-old) biofilms was examined using a semiquantitative plate assay, and the effect on mature (24 h-old) biofilms was observed under a confocal laser scanning microscope (CLSM). RESULTS: The derivatives potently suppressed the growth of Staphylococcus epidermidis. The MIC values of the derivatives H2-10, H2-12, H2-20, H2-29, H2-27, and H2-28 on S epidermidis ATCC 35984 were 24.3, 6.5, 6.2, 3.3, 3.1, and 1.5 µg/mL, respectively. The MBC values of these derivatives were 48.6, 52.2, 12.4, 52.6, 12.4, and 6.2 µg/mL, respectively. The derivatives killed all bacteria in immature (6 h-old) biofilms and eliminated the biofilm proliferation. The derivatives also displayed strong bactericidal activities toward cells in mature (24 h-old) biofilms, whereas they showed low cytotoxicity and hemolytic activity toward Vero cells and human erythrocytes. CONCLUSION: The bactericidal and biofilm-killing activities of the new anti-YycG compounds were significantly better than the parent Compound 2.

Involvement of microRNA/cystine/glutamate transporter in cold-stressed gastric mucosa injury.

Stress ulcers are complicated by severe trauma and other critical diseases, the mechanism of which remains unclear. An increasing number of studies have shown that microRNAs (miRNAs) are important regulators of stress responses such as hypoxia, abnormal temperature, and inflammation. The evidence indicates that miRNAs are also involved in regulating stress-induced ulcers. Recently, we demonstrated that gastric mucosal injury induced by aspirin is related to the reduction of glutamate levels by inhibition of cystine/glutamate transporter (xCT) activity. In the present study, the effect of a miRNA/xCT on gastric mucosal injury induced by cold stimulation was investigated. We found that cold stimulation induced gastric mucosa injury with a reduction in glutamate levels and xCT activity and upregulation of miR-143, miR-152, and miR-181 expression. Exogenous glutamate significantly alleviated gastric mucosa injury by cold stimulation. In vitro experiments demonstrated that treatment with miR-143, miR-152, or miR-181 mimics directly induced cell damage. The effects of these mimics were alleviated by exogenous glutamate. The present study suggests that miR-143, miR-152, and miR-181 are involved in cold stimulation-induced acute gastric mucosal injury. Furthermore, the regulatory effect of miRNAs on gastric mucosa injury induced by cold stimulation is related to a decrease in glutamate release by reduction of cystine/glutamate transporter activity.

Novel compound heterozygous mutation of SLC12A3 in Gitelman syndrome co-existent with hyperthyroidism: A case report and literature review.

BACKGROUND: Gitelman syndrome (GS) is a rare inherited autosomal recessive tubulopathy, characterized clinically by hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis, and is caused by an inactivating mutation in SLC12A3. GS is prone to misdiagnosis when occurring simultaneously with hyperthyroidism. It is important to consider the possibility of other diseases when hyperthyroidism is combined with hypokalemia, which is difficult to correct. CASE SUMMARY: A female patient with hyperthyroidism complicated with limb weakness was diagnosed with thyrotoxic hypokalemic periodic paralysis for 4 mo. However, the patient's serum potassium level remained low despite sufficient potassium replacement and remission of hyperthyroidism. GS was confirmed by whole exome and Sanger sequencing. Gene sequencing revealed compound heterozygous mutations of c.488C>T (p.Thr163Met), c.2612G>A (p.Arg871His), and c.1171_1178dupGCCACCAT (p.Ile393fs) in SLC12A3. Protein molecular modeling was performed to predict the effects of the identified missense mutations. All three mutations cause changes in protein structure and may result in abnormal protein function. All previously reported cases of GS coexisting with autoimmune thyroid disease are reviewed. CONCLUSION: We have identified a novel compound heterozygous mutation in SLC12A3. The present study provides new genetic evidence for GS.

Homogenate Extraction of Dihydroartemisinin from Artemisia Hedinii and Its Antifungal Activity.

BACKGROUND: Artemisia hedinii is a well-known traditional Chinese medicine. It can be used to extract dihydroartemisinin (DHA). OBJECTIVE: The purpose of this study was to explore the optimal conditions for the homogenate extraction of DHA from A. hedinii and the antifungal activity of DHA. METHODS: In this study, single-factor experiments and the response surface method were used to determine the optimal extraction conditions of crude extract and DHA. The method of spore germination was used to study the antifungal activity of DHA on Alternaria alternata. RESULTS: The optimal conditions were found as follows: ratio of liquid to material 22 mL/g; extraction time 60 s; and soaking time 34 min. Under these conditions, extraction yield of DHA was (1.76 ± 0.04%). When the concentrations of crude extract were 0.5 and 8 mg/mL, the spore germination inhibition rates of A. alternata were (17.00 ± 2.05%) and (92.56 ± 2.01%), which were 3.34 and 1.15 times that of the DHA standard, respectively. CONCLUSIONS: Homogenate extraction technology is a fast and efficient method for extracting DHA from A. hedinii. The crude extract has significant antifungal activity against A. alternata and is inexpensive, providing possible DHA usage in the prevention and treatment of plant pathogenic fungi. HIGHLIGHTS: The optimum conditions of the extraction of DHA from A. hedinii by homogenate extraction were obtained. DHA has antifungal activity against A. alternata. Compared with pure DHA, the crude extract has stronger antifungal activity against A. alternata.

Ferroptosis-Associated Classifier and Indicator for Prognostic Prediction in Cutaneous Melanoma.

Ferroptosis plays a critical role in different types of cancers, but the prognostic impact of ferroptosis in cutaneous melanoma remains lacking. Therefore, ferroptosis-related genes (FRGs) were firstly obtained from the FerrDb database and the differentially expressed FRGs were identified by the "limma" algorithm. Next, the prognostic differentially expressed FRGs were screened out by univariate Cox regression, which were subsequently used to cluster melanomas into two subtypes (clusters A and B). Besides, the Boruta algorithm and principal component analysis (PCA) were performed to build a 15-FRGs indicator, which can robustly predict patients' overall survival (OS) and be considered as an independent prognostic factor in melanoma. The melanoma patients were further divided into high- and low-FRGs score groups. The high score group have a good prognosis, with higher T cell immune infiltrating and lower mutation frequencies in NRAS, KRAS, and NF1. Finally, we discovered that many immune processes and several chemotherapy drugs were closely associated with FRGs score. Thus, our study provides a novel ferroptosis-associated classifier and indicator to predict the prognosis of melanoma. Besides, we identified several potential chemotherapy drugs to induce ferroptosis and could supply additional effective treatments.