Polyketides with α-glucosidase inhibitory and neuroprotective activities from Aspergillus versicolor associated with Pedicularis sylvatica.

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB.

Objective: This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40, CD80, CD83, and CD86. Method: This was a cross-sectional study in which patients were divided into a natural history group (namely NH group), a long-term oral nucleoside analogs treatment group (namely NA group), and a plateau-arriving group (namely P group). The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results: In total, 143 patients were enrolled (NH group, n = 49; NA group, n = 47; P group, n = 47). The results demonstrated that CD141/CD1c double negative myeloid dendritic cell (DNmDC)/lymphocytes and monocytes (%) in P group (0.041 [0.024, 0.069]) was significantly lower than that in NH group (0.270 [0.135, 0.407]) and NA group (0.273 [0.150, 0.443]), and CD86 mean fluorescence intensity of DNmDCs in P group (1832.0 [1484.0, 2793.0]) was significantly lower than that in NH group (4316.0 [2958.0, 5169.0]) and NA group (3299.0 [2534.0, 4371.0]), Adjusted P all < 0.001. Conclusion: Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Roxadustat Versus Erythropoietin: The Comparison of Efficacy in Reversing Ventricular Remodeling in Dialysis Patients with Anaemia.

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months.

Quality control and external quality assessment for the independent clinic-based evaluation of point-of-care testing to detect Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in eight countries.

BACKGROUND: Sexually transmitted infections caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) remain significant global health problems. The World Health Organization (WHO) has recently conducted a multi-faceted, multi-country validation study (ProSPeRo), which included an evaluation of the Xpert CT/NG and Xpert TV assays on the GeneXpert system (Cepheid, Sunnyvale, Ca., USA) in clinic-based settings across eight countries. To support the study, a training and quality management system was implemented and evaluated. METHODS: A comprehensive training program for the study was developed. Quality control (QC) and external quality assessment (EQA) samples were provided by an accredited quality assurance provider. QC testing was conducted at 14 point-of-care testing (POCT) clinics, while EQA samples were tested by the POCT sites and a reference laboratory supporting each clinic. RESULTS: For QC testing, concordance with the expected results for CT and NG was > 99% and rates of unsuccessful tests were < 4%. For TV testing, concordance was similar (97%), but rates of unsuccessful tests were high (18%), particularly in the 'TV negative' sample. For EQA testing initially conducted in 2018, concordance was 100% for CT and NG, and 90% for TV for the reference laboratory group (which used non-GeneXpert systems). Concordance for the POCT group was also high (> 94%) for all analytes, but this cohort (which used GeneXpert systems) exhibited a high rate of unsuccessful TV tests. All but one of these unsuccessful tests was subcategorised as 'invalid'. CONCLUSIONS: The high level of concordance for QC and EQA testing confirm that the trained operators at the POC clinical sites were competent to conduct POC testing and that the training and quality systems implemented for the ProSPeRo study were effective. The quality materials used were satisfactory for CT and NG but exhibited poor performance for TV testing on the GeneXpert system. The WHO should continue to work with industry and EQA providers to provide improved materials that are reliable, stable and cost effective for quality management, as it seeks to rollout molecular-based STI POCT in non-laboratory-based settings. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee.

Synthesis, structure, theoretical calculation and antibacterial property of two novel Zn(II)/Ni(II) compounds based on 3, 5-dichlorosalicylaldehyde thiocarbamide ligand.

Two new compounds namely [Zn(L1)phen]31 and Ni(L1)phen(MeOH) 2 (L1 = 3, 5-dichlorosalicylaldehyde thiosemicarbazone) were synthesized by the slow evaporation method at room temperature. The structure of ligand L1 was determined using 1H NMR and 13C NMR spectra. X-ray single crystal diffraction analysis revealed that compounds 1-2 can form 3D supramolecular network structures through π···π stacking and hydrogen bonding interactions. The DFT calculation shows that the coordination of ligand and metal is in good agreement with the experimental results. Hirshfeld surface analysis revealed that H…H and Cl…H interactions were the predominant interactions in compounds 1-2. Energy framework analysis indicated that dispersion energy played a dominant role in the energy composition of compounds 1-2. The inhibitory effects of compounds 1-2 against Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA) were tested using the paper disk diffusion method (1: E. coli: 18 mm, MRSA: 17 mm, 2: E. coli: 15 mm, MRSA: 16 mm). Ion releasing experiments were conducted to assess the ion release capacity of compounds 1-2 (Zn2+, 4 days, 38.33 µg/mL; Ni2+, 4 days, 29.12 µg/mL). Molecular docking demonstrated the interaction modes of compounds 1-2 with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and dihydrofolate reductase (DHFR) in bacteria, involving hydrophobic, stacking, hydrogen bonding and halogen bonding interactions. The generation of reactive oxygen species (ROS) in bacteria under the presence of compounds 1-2 were evaluated using a fluorescent dye known as dichlorodihydrofluorescein diacetate (DCFH-DA). Potential antibacterial mechanisms of compounds 1-2 were proposed.

The ratio of neutrophils to lymphocytes effectively predicts clinical outcomes in idiopathic membranous nephropathy.

BACKGROUND: Systemic inflammatory indicators are important in the prognoses of various diseases. Such indicators, including the neutrophil-to-lymphocyte ratio (NLR), can be meaningful in predicting the clinical outcome in patients diagnosed with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS: 112 IMN patients diagnosed by renal biopsy were recruited retrospectively. The endpoint was defined as a combination of partial and complete remission. Statistical analysis determined the independent factors associated with clinical remission and the predictive utility of NLR. RESULTS: Within the 12-month follow-up period, 72 patients achieved clinical remission after treatment. Univariate analysis identified significant differences in serum albumin, estimated glomerular filtration rate (eGFR), proteinuria, neutrophil count, and NLR between the remission group and the non-remission group (all p < 0.05). Cox proportional hazards indicated that elevated eGFR (HR 1.022, 95% CI (1.009 - 1.035), p = 0.001), lower NLR (HR 0.345, 95% CI (0.237 - 0.501), p = 0.0001), and decreased proteinuria (HR 0.826, 95% CI (0.693 - 0.984), p = 0.032) were protective elements for remission. With an optimal cut-off value of 2.61, the pre-treatment NLR had an excellent ability to identify the remission (area under the curve (AUC), 0.785). Participants were separated into low- and high-NLR groups by using 2.61. Kaplan-Meier survival curves revealed significantly higher remission rates in the lower group (p < 0.0001). CONCLUSION: The NLR is an effective indicator for predicting clinical remission in patients with IMN.

Treatment of maternal syphilis for preventing congenital syphilis: an observational study of adherence to treatment recommendation in Suzhou, China, 2019-2021.

BACKGROUND: China is one of the countries that set the goal to eliminate mother-to-child transmission (EMTCT) of syphilis by a target date. Active screening for syphilis among pregnant women, followed by effective treatment of maternal syphilis, is critical for achieving the goal. The China health authority issued national implementation protocols to guide EMTCT practice in health facilities. METHODS: Within a cohort of infants born to mothers infected with syphilis, we obtained the data of regimens used for treatment of maternal syphilis from the National Information System of Prevention of Mother-to-Child Transmission of HIV, Syphilis and Hepatitis B, and analysed the physician's treatment behaviour and its associated factors in a public hospital in Suzhou of China. RESULTS: A total of 450 pregnant women who were positive for treponemal or non-treponemal antibody, or had previous infection with syphilis were included into the study for analysis. Of them, 260 (57.8%) were positive for both treponemal and non-treponemal antibodies (syphilis seropositivity), and 353 (78.4%) were treated for syphilis according to the protocol in which 123 (34.8%) were treated with two courses. Non-adherence to treatment recommended by the protocol for maternal syphilis was significantly associated with antenatal visits in the third trimester (AOR 6.65, 95% CI 2.20-20.07, P =0.001), being positive only for a treponemal test (AOR 5.34, 95% CI 3.07-9.29, P <0.001) or having a syphilis infection before the pregnancy (AOR 2.05, 95% CI 1.14-3.69, P =0.017), whereas the uptake of treatment for two treatment courses was associated with attending antenatal care in 2020 or before (AOR 3.49, 95% CI 1.89-6.42, P <0.001), being positive for treponemal and non-treponemal tests (AOR 5.28, 95% CI 2.78-10.06, P <0.001) or having non-treponemal antibody titre of ≥1:8 (AOR 3.71, 95% CI 1.77-7.78, P =0.001). CONCLUSIONS: Implementation of the current recommendation to offer a universal treatment for syphilis among all pregnant women who are shown to be positive for a treponemal test alone is challenging in some clinical settings in China.

Activation of acetyl-CoA synthetase 2 mediates kidney injury in diabetic nephropathy.

Albuminuria and podocyte injury are the key cellular events in the progression of diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is a nucleocytosolic enzyme responsible for the regulation of metabolic homeostasis in mammalian cells. This study aimed to investigate the possible roles of ACSS2 in kidney injury in DN. We constructed an ACSS2-deleted mouse model to investigate the role of ACSS2 in podocyte dysfunction and kidney injury in diabetic mouse models. In vitro, podocytes were chosen and transfected with ACSS2 siRNA and ACSS2 inhibitor and treated with high glucose. We found that ACSS2 expression was significantly elevated in the podocytes of patients with DN and diabetic mice. ACSS2 upregulation promoted phenotype transformation and inflammatory cytokine expression while inhibiting podocytes' autophagy. Conversely, ACSS2 inhibition improved autophagy and alleviated podocyte injury. Furthermore, ACSS2 epigenetically activated raptor expression by histone H3K9 acetylation, promoting activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Pharmacological inhibition or genetic depletion of ACSS2 in the streptozotocin-induced diabetic mouse model greatly ameliorated kidney injury and podocyte dysfunction. To conclude, ACSS2 activation promoted podocyte injury in DN by raptor/mTORC1-mediated autophagy inhibition.

Identification of TMEM53 as a novel SADS-CoV restriction factor that targets viral RNA-dependent RNA polymerase.

ABSTRACTZoonotic transmission of coronaviruses (CoVs) poses a serious public health threat. Swine acute diarrhea syndrome coronavirus (SADS-CoV), originating from a bat HKU2-related CoV, causes devastating swine diseases and poses a high risk of spillover to humans. Currently, licensed therapeutics that can prevent potential human outbreaks are unavailable. Identifying the cellular proteins that restrict viral infection is imperative for developing effective interventions and therapeutics. We utilized a large-scale human cDNA screening and identified transmembrane protein 53 (TMEM53) as a novel cell-intrinsic SADS-CoV restriction factor. The inhibitory effect of TMEM53 on SADS-CoV infection was found to be independent of canonical type I interferon responses. Instead, TMEM53 interacts with non-structural protein 12 (NSP12) and disrupts viral RNA-dependent RNA polymerase (RdRp) complex assembly by interrupting NSP8-NSP12 interaction, thus suppressing viral RdRp activity and RNA synthesis. Deleting the transmembrane domain of TMEM53 resulted in the abrogation of TMEM53-NSP12 interaction and TMEM53 antiviral activity. Importantly, TMEM53 exhibited broad antiviral activity against multiple HKU2-related CoVs. Our findings reveal a novel role of TMEM53 in SADS-CoV restriction and pave the way to host-directed therapeutics against HKU2-related CoV infection.

Associations of Chlamydia trachomatis serology with fertility-related and pregnancy adverse outcomes in women: a systematic review and meta-analysis of observational studies.

BACKGROUND: Chlamydia trachomatis (CT) infection has an increased risk for fertility-related and pregnancy adverse outcomes partly due to mechanisms related to a pro-inflammatory response to CT-, or cHSP60-induced delayed hypersensitivity. This study aimed to assess the evidence on the association between CT serology and adverse outcomes. METHODS: PubMed/Medline, Embase and Web of Science databases were searched for observational studies on the association of CT-specific antibodies (e. g. IgG, IgA, IgM, etc.) with infertility, tubal factor infertility (TFIF), ectopic pregnancy (EP), spontaneous abortion (SA), or preterm labor (PL) that were published from database inception to 31 August 2022. Pooled adjusted odds ratios or relative risks with corresponding 95% confidence intervals were calculated using a random effects model. This study was registered with PROSPERO (CRD42022368366). FINDINGS: We identified 128 studies that met the inclusion criteria, comprising 87 case-control, 34 cross-sectional and 7 cohort studies, for a total of 167 records involving 128,625 women participants included into the meta-analyses. Based on the adjusted estimates, it was found that CT-specific IgG was significantly associated with TFIF (pooled adjusted OR = 2.09, 95% CI 1.33-3.27, I2 = 63.8%) or EP (pooled adjusted OR = 3.00, 95% CI 1.66-5.40, I2 = 93.0%). Analyses of the unadjusted estimates indicated significant associations between CT-specific IgG and infertility, TFIF, EP or SA (four pooled unadjusted ORs ranging between 1.60 and 5.14, I2 ranging between 40% and 83%); IgA and infertility, TFIF, EP (three pooled unadjusted ORs ranging between 3.64 and 4.91, I2 ranging between 0% and 74%); IgM and TFIF (pooled unadjusted OR = 5.70, 95% CI 1.58-20.56, I2 = 56%); or cHSP60 and TFIF (pooled unadjusted OR = 7.83, 95% CI 5.42-11.31, I2 = 49%). INTERPRETATION: A broad range of CT-specific antibodies have been studied in association with fertility-related and pregnancy adverse outcomes. However, our study identified a low- or moderate-quality evidence for an association of CT serology with the outcomes. There are substantial research gaps in relation to the clinical implications of CT serological biomarkers. FUNDING: The work was supported by the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021).

Ergostane-type sterols and sesquiterpenes with anti-neuroinflammatory activity from a Nigrograna species associated with Clematis shensiensis.

Nigrograna sp. LY66, an endophytic fungus associated with the herbal medicinal plant Clematis shensiensis, produced four undescribed steroids, nigergostanes A-D (1-4), including an unusual ketal-containing nigergostane (1), and four undescribed sesquiterpenoids decorated with cyclohexanone motifs, nigbisabolanes A-D (7-10), along with three known compounds, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one (5), ergosta-5,7,22-trien-3ß-ol (6), and curculonone A (11). The structures and absolute configurations of these undescribed compounds were confirmed using spectroscopic data (NMR and HRESIMS), modified Mosher's method, and ECD experiments. Additionally, compounds 5 and 8 displayed significant inhibition of nitric oxide generation in lipopolysaccharide-induced BV-2 microglial cells with IC50 values of 2.8 and 2.7 µM, respectively, and is thus more potent than that of the positive control, quercetin (IC50 = 8.77 µM). A molecular docking study revealed that 23-OH of 5 binds to the Y347 residue of inducible nitric oxide synthase (iNOS), whereas the 2-OH and 9,10-diol moieties of 8 bind to R381 and W463 and haeme residues of iNOS, respectively, which has rarely been reported in previous studies. These findings provide a set of undescribed lead compounds that can be developed into anti-neuroinflammatory agents.

The clinical significance of macrolide resistance in pediatric Mycoplasma pneumoniae infection during COVID-19 pandemic.

Background: Mycoplasma pneumoniae (MP) is a commonly occurring pathogen causing community-acquired pneumonia (CAP) in children. The global prevalence of macrolide-resistant MP (MRMP) infection, especially in Asian regions, is increasing rapidly. However, the prevalence of MRMP and its clinical significance during the COVID-19 pandemic is not clear. Methods: This study enrolled children with molecularly confirmed macrolide-susceptible MP (MSMP) and MRMP CAP from Beijing Children's Hospital Baoding Hospital, Capital Medical University between August 2021 and July 2022. The clinical characteristics, laboratory findings, chest imaging presentations, and strain genotypes were compared between patients with MSMP and MRMP CAP. Results: A total of 520 hospitalized children with MP-CAP were enrolled in the study, with a macrolide resistance rate of 92.7%. Patients with MRMP infection exhibited more severe clinical manifestations (such as dyspnea and pleural effusion) and had a longer hospital stay than the MSMP group. Furthermore, abnormal blood test results (including increased LDH and D-dimer) were more common in the MRMP group (P<0.05). Multilocus variable-number tandem-repeat analysis (MLVA) was performed on 304 samples based on four loci (Mpn13-16), and M3562 and M4572 were the major types, accounting for 74.0% and 16.8% of the strains, respectively. The macrolide resistance rate of M3562 strains was up to 95.1%. Conclusion: The prevalence of MRMP strains in hospitalized CAP patients was extremely high in the Baoding area, and patients infected with MRMP strains exhibited more severe clinical features and increased LDH and D-dimer. M3562 was the predominant resistant clone.

Using pooled urogenital, anorectal and oropharyngeal specimens to detect Chlamydia trachomatis and Neisseria gonorrhoeae among men who have sex with men in China: a multisite diagnostic accuracy study.

OBJECTIVES: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at both urogenital and extragenital sites has been recommended in many countries. Testing of the infections using pooled specimens from urogenital and extragenital sites offer the opportunity to shorten the testing time and reduce the testing cost. Ex-ante pooling is placing the original single-site specimens in a tube with transport media, while ex-post pooling is making a pool of the transport media from both anorectal and oropharyngeal specimens and the urine. This study aimed to conduct a multisite performance evaluation of two pool-specimen approaches (ex-ante and ex-post) in detection of CT and NG using the Cobas 4800 platform among men who have sex with men (MSM) in China. DESIGN: Diagnostic accuracy study. SETTING, PARTICIPANTS AND OUTCOME MEASURES: Participants were recruited from MSM communities at six cities in China. Two oropharyngeal and anorectal swabs collected by clinical staff and 20 mL first-void urine collected by the participant himself were used for evaluating sensitivity and specificity. RESULTS: A total of 1311 specimens were collected from 437 participants in six cities. The sensitivities of ex-ante pooling approach as compared with single-specimen approach (reference standard) were 98.7% (95% CI, 92.7% to 100.0%) for detection of CT and 89.7% (95% CI, 75.8% to 97.1%) for NG, and the specificities were 99.5% (95% CI, 98.0% to 99.9%) and 98.7% (95% CI, 97.1% to 99.6%), respectively. The sensitivities of ex-post pooling approach were 98.7% (95% CI, 92.7% to 100.0%) for CT and 100.0% (95% CI, 91.0% to 100.0%) for NG, and the specificities were 100.0% (95% CI, 99.0% to 100.0%) and 100.0% (95% CI, 99.1% to 100.0%), respectively. CONCLUSIONS: The ex-ante and ex-post pooling approaches show good sensitivity and specificity in detecting urogenital and extragenital CT and/or NG, indicating that these approaches can be used in epidemiological surveillance and clinical management of CT and NG infections, particularly among MSM population.

Knowledge on Chlamydia trachomatis and Acceptance to Testing for It Among Young Students in China.

BACKGROUND: Actively screening for Chlamydia trachomatis (CT) is important for young people because of a high prevalence of asymptomatic infection in this population. This study aimed to investigate knowledge on CT and preference to the screening services for CT among young students in China. METHODS: From June to July 2022, a web-based questionnaire survey was conducted to collect information on sociodemographic characteristics, sexual behaviors, knowledge of CT, previous testing for CT, and preference to platform of testing for CT among Chinese young students. An online home-based self-sampling test (HBSST) service was offered free of charge if the participant was willing to be tested for CT. Statistical analyses included descriptive analysis, χ 2 test, and multivariable logistic regression. RESULTS: Of 520 participants, 419 (80.6%) were aged between 16 and 24 years, 235 (45.2%) reported having sexual experience in the past, and 27 (5.2%) being tested before for CT. Slightly higher than 10% (57/520) of students were knowledgeable about CT. About one-third (36.9%) expressed their willingness to have a testing for CT but majority of them (63.1%) preferred to a free testing. Having sexual experience was significantly associated with the willingness to take the HBSST service (adjusted odds ratio, 2.96; 95% confidence interval, 1.92-4.58). A total of 139 (26.7%) participants requested the HBSST service online and 43.2% (60/139) returned the specimen for testing, in which 2 positives (3.3%) were found. CONCLUSIONS: The knowledge on CT and the previous uptake or current willingness to have a testing for CT was low among Chinese young students.

Review on the systems biology research of Yin-deficiency-heat syndrome in traditional Chinese medicine.

Traditional Chinese medicine (TCM) is a systematic medical method that has existed for more than 3,000 years. Unlike Western medicine, the disease diagnosis in TCM is carried out by inspection, auscultation, olfaction, interrogation, and palpation. The patient is then treated according to the disease and corresponding TCM syndrome. However, the development of Chinese medicine is stagnated, partially because it can be influenced by subjective factors, such as the experience and knowledge of TCM practitioners, and there is a lack of relevant biological research on TCM syndromes. Yin-deficiency-heat (YDH) syndrome in TCM is characterized by a series of pathological changes caused by the insufficiency of Yin-fluid, inability to moisturize, and the failure to suppress Yang. In recent years, systems biology research on TCM syndromes has gradually become the focus of TCM research, including syndrome differentiation and functional research using systems biology methodologies such as proteomics, transcriptomics, and metabolomics. This journal aims to publish a series of issues on the systems biology research of TCM syndromes that can provide biological indicators for the syndrome differentiation of YDH syndrome and can provide perspectives on the biological research of YDH syndrome.

Developmental characteristics of visual evoked potentials to different stimulation in normal children.

OBJECTIVE: To determine the developmental characteristics of flash visual evoked potentials (FVEP) and pattern-reversal visual evoked potentials (PVEP) of healthy children. METHODS: The data were collected with a Keypoint Workstation 9033A07; 168 children (2 months-13 years) were tested with FVEP and 101 (4-13 years) were tested with PVEP. RESULTS: A triphasic waveform with clear components (N2, P2, and N3) was recorded steadily after 1 year, with occurrence rates over 97% at all frequencies. FVEP latency significantly decreased with age. The amplitude difference of FVEP was greater for binocular than monocular fields. FVEP amplitude increased and amplitude differences decreased with stimulation frequency. The occurrence rate of PVEP was 100% after 4 years, and PVEP latency was significantly prolonged with age. N75 and P100 amplitudes and the N75-P100 amplitude difference increased with field of vision. CONCLUSION: FVEP can be evoked in normal children at less than 2 Hz. Stimulation frequency can be adjusted to improve early detection and verification of subclinical lesions. The PVEP waveform is simple and stable, and its results are easier to analyze and interpret than FVEP, but it is limited by visual acuity and fixation force, whereas FVEP is affected less by visual acuity. but it is necessary to establish normal reference values of each age in each laboratory because of complicated analysis. According to the specific situation of the patient (vision, fixation) and clinical demand, we need to choose the right stimulation.

Deposition of platelet-derived microparticles in podocytes contributes to diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the developed world. Podocyte injury is a critical cellular event involved in the progression of DN. Our previous studies demonstrated that platelet-derived microparticles (PMPs) mediated endothelial injury in diabetic rats. This study aimed to investigate whether PMPs are deposited in podocytes and to assess their potential effects on podocyte injury in DN. METHODS: The deposition of PMPs in podocytes was assessed by immunofluorescent staining and electron microscopy. The changes in renal pathology and ultra-microstructure were assessed by periodic acid-Schiff staining and electron microscopy, respectively. The expression of inflammatory cytokines and extracellular matrix proteins was measured by immuno-histochemical staining and western blot. RESULTS: PMPs were widely deposited in podocytes of glomeruli in diabetic patients and animal models and closely associated with DN progression. Interestingly, aspirin treatment significantly inhibited the accumulation of PMPs in the glomeruli of diabetic rats, alleviated mesangial matrix expansion and fusion of foot processes, and decreased the protein expression of inflammatory cytokines and extracellular matrix secretion. An in vitro study further confirmed the deposition of PMPs in podocytes. Moreover, PMP stimulation induced the phenotypic transition of podocytes through decreased podocin protein expression and increased protein expression of α-SMA and fibronectin, which was correlated with increased production of inflammatory cytokines. CONCLUSION: Our findings demonstrated for the first time that the deposition of PMPs in podocytes contributed to the development of DN.

Meropenem for children with severe pneumonia: Protocol for a randomized controlled trial.

Background: Pneumonia, caused by infection or other factors, seriously endangers the health of children. Meropenem is an effective broad-spectrum antibiotic using in the treatment of infectious diseases. In the therapy of pneumonia, meropenem is mostly employed for the treatment of moderate to severe pneumonia. Previously, we established a population pharmacokinetics (PPK) model for meropenem in pediatric severe infection and simulated the control rate of the time during which the free plasma concentration of meropenem exceeds the minimum inhibitory concentration (MIC) is 70% of the dosing interval (70% fT > MIC). Therefore, we plan to conduct a multicenter randomized controlled trial (RCT) to compare the efficacy and safety between conventional regimen and model regimen for meropenem in pediatric severe pneumonia. Methods: One hundred patients (aged 3 months to 15 years) will be recruited in this RCT. They will be assigned randomly (at a 1:1 ratio) to a conventional treatment group (20 mg/kg, q8h, with 0.5-1 h infusion) and a model treatment group (20 mg/kg, q8 h, with 4 h infusion). The primary outcome will be 70% fT > MIC. Secondary outcomes will be the prevalence of meropenem therapy failure, duration of antibiotic therapy, changes in levels of inflammatory indicators, changes in imaging examination results, and prevalence of adverse events. Ethical approval of our clinical trial has been granted by the ethics committee of Beijing Children's Hospital ([2022]-E-133-Y). This trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200061207). Discussion: Based on our previous PPK data, we have designed this RCT. It is hoped that it will promote rational use of antibacterial drugs in children suffering from severe pneumonia. Clinical Trial Registration: http://www.chictr.org.cn identifier, ChiCTR2200061207.

Using a machine learning model to predict the development of acute kidney injury in patients with heart failure.

Background: Heart failure (HF) is a life-threatening complication of cardiovascular disease. HF patients are more likely to progress to acute kidney injury (AKI) with a poor prognosis. However, it is difficult for doctors to distinguish which patients will develop AKI accurately. This study aimed to construct a machine learning (ML) model to predict AKI occurrence in HF patients. Materials and methods: The data of HF patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database was retrospectively analyzed. A ML model was established to predict AKI development using decision tree, random forest (RF), support vector machine (SVM), K-nearest neighbor (KNN), and logistic regression (LR) algorithms. Thirty-nine demographic, clinical, and treatment features were used for model establishment. Accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) were used to evaluate the performance of the ML algorithms. Results: A total of 2,678 HF patients were engaged in this study, of whom 919 developed AKI. Among 5 ML algorithms, the RF algorithm exhibited the highest performance with the AUROC of 0.96. In addition, the Gini index showed that the sequential organ function assessment (SOFA) score, partial pressure of oxygen (PaO2), and estimated glomerular filtration rate (eGFR) were highly relevant to AKI development. Finally, to facilitate clinical application, a simple model was constructed using the 10 features screened by the Gini index. The RF algorithm also exhibited the highest performance with the AUROC of 0.95. Conclusion: Using the ML model could accurately predict the development of AKI in HF patients.