Unraveling the link between childhood maltreatment and depression: Insights from the role of ventral striatum and middle cingulate cortex in hedonic experience and emotion regulation.

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

Effects of irrigation fluid temperature during flexible ureteroscopic holmium laser lithotripsy on postoperative fever and shivering: a randomized controlled trial.

BACKGROUND: Flexible ureteroscopic holmium laser lithotripsy is used to treat urinary tract calculi, but postoperative complications include shivering, fever and infection. To investigate the effects of irrigation fluid temperature on postoperative complications. METHODS: This randomized controlled trial included 120 consecutive patients undergoing flexible ureteroscopic holmium laser lithotripsy at the Urology Department, Suining Central Hospital, Sichuan, China between January 2017 and July 2019. Patients were randomized 1:1:1 into three groups (17 °C, 27 °C or 37 °C). Primary outcome was fever incidence (body temperature > 37.5 °C) within 48 h after surgery. Secondary outcomes included shivering incidence during recovery from anesthesia, white blood cell count (WBC), serum procalcitonin (PCT) and incidence of suspected infection (temperature > 38.5 °C and PCT > 0.5 µg/L). RESULTS: There were 108 patients, (17 °C group, n = 36; 27 °C group, n = 35; 37 °C group, n = 37), received flexible ureteroscopic holmium laser lithotripsy and analyzed. Age, gender distribution, body mass index, ASA grade, stone burden, preoperative creatinine, preoperative core temperature and irrigation fluid volume did not differ significantly between groups. 17 °C, 27 °C and 37 °C groups exhibited significant differences in the incidences of postoperative fever (38.9% vs. 17.1% vs. 13.5%) and shivering (22.2% vs. 5.7% vs. 2.7%) (p < 0.05 for all pairwise comparisons). There was no significant difference of WBC, PCT and incidence of suspected infection in 37 °C or 27 °C group compared with 17 °C group. One case each of flash pulmonary edema and bleeding occurred in 37 °C group. CONCLUSION: Warming the irrigation fluid can reduce the incidence of postoperative fever and shivering, but further studies are needed to determine the optimal temperature. Trial registration The trial was registered at the Chinese Clinical Trials Registry and allocated as ChiCTR2000031683. The trial was registered on 07/04/2020 and this was a retrospective registration.

Temporal dynamics of activated sludge bacterial communities in two diversity variant full-scale sewage treatment plants.

Bacterial community in activated sludge (AS) is diverse and highly dynamic. Little is known about the mechanism shaping bacterial community composition and dynamics of AS and no study had quantitatively compared the contribution of abiotic environmental factors and biotic associations to the temporal dynamics of AS microbial communities with significantly different diversity. In this study, two full-scale sewage treatment plants (STPs) with distinct operational parameters and influent composition were sampled biweekly over 1 year to reveal the correlating factors to whole and sub-groups of AS bacterial community diversity and dynamics. The results show that the bacterial communities of the two STPs were entirely different and correlated with the influent composition and operating configurations. Bacterial associations represented by cohesion metrics and the environmental factor temperature were the primary correlated factors to the temporal bacterial community dynamics within each STP. The STP with high diversity and evenness could treat influent with higher suspended solid and a shorter sludge retention time, and was less correlated with environmental factors, implying the importance of diversity for AS system.

Differential expression profile of long non-coding RNA in cardiomyocytes autophagy induced by angiotensin II.

Autophagy is a ubiquitous intracellular process for cellular homeostasis maintenance by recycling damaged protein and organelles. Dysregulation of cardiomyocytes autophagic activity is implicated in various heart diseases. Recent studies had demonstrated that long non-coding RNAs (lncRNAs) played crucial roles on modulation of autophagic activity. In this study, we first established an angiotensin II-induced autophagy model on neonatal rat cardiomyocytes. Western blot assay confirmed that the expression of Beclin 1 and the conversion of soluble LC3-I to lipid bound LC3-II were significantly increased at 12 h after angiotensin II stimulation, but the cardiomyocytes surface area and hypertrophic markers expression had no significant change. Then microarray analysis and real-time PCR were applied to detect differentially expressed lncRNAs during cardiomyocytes autophagy. A total of 1,249 lncRNAs were determined as differentially expressed, including 700 upregulated lncRNAs and 549 downregulated lncRNAs. LncRNAs subgroup analysis showed there were 43 transcribed ultra-conserved noncoding RNAs (T-UCRs) differentially expressed in cardiomyocytes autophagy, of which 26 T-UCRs were upregulated and 17 T-UCRs were downregulated. Bioinformatics analysis further showed that 94 differentially expressed lncRNAs contained potential binding sites of miR-22, a pro-hypertrophic and pro-autophagic microRNA. Therefore, these differentially expressed lncRNAs might play critical roles in cardiomyocytes autophagy. This finding would provide an experimental basis for future investigation on ischemic heart disease.

Diagnostic Value of Cerebrospinal Fluid T-SPOT.TB for Tuberculousis Meningitis in China.

The aim of this study was to evaluate the diagnostic value of the cerebrospinal fluid (CSF) T-SPOT.TB test for the diagnosis of TB meningitis (TBM). A retrospective analysis of 96 patients with manifested meningitis was conducted; T-SPOT.TB test was performed for diagnosing TBM to determine the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A receiver operating characteristic (ROC) curve was also drawn to assess the diagnostic accuracy. The sensitivity, specificity, PPV, and NPV of CSF T-SPOT.TB test were 97.8%, 78.0%, 80.3%, and 97.5%, respectively, for 52 patients (54.2%) of the 96 enrolled patients. The area under the curve (AUC) was 0.910, and the sensitivities of CSF T-SPOT.TB for patients with stages I, II, and III of TBM were 96.7%, 97.2%, and 98.9%, respectively. CSF T-SPOT.TB test is a rapid and accurate diagnostic method with higher sensitivity and specificity for diagnosing TBM.

Role of Diabetes Mellitus on Treatment Effects in Drug-susceptible Initial Pulmonary Tuberculosis Patients in China.

We assessed the role of diabetes mellitus (DM) on treatment effects in drug-susceptible initial pulmonary tuberculosis (PTB) patients. A prospective study was conducted in eight provinces of China from October 2008 to December 2010. We enrolled 1,313 confirmed drug-susceptible initial PTB patients, and all subjects received the treatment regimen (2H3R3E3Z3/4H3R3) as recommended by the national guidelines. Of the 1,313 PTB patients, 157 (11.9%) had DM; these patients had more sputum smear-positive rates at the end of the second month [adjusted odds ratios (aOR) 2.829, 95% confidence intervals (CI) 1.783-4.490], and higher treatment failure (aOR 2.120, 95% CI 1.565-3.477) and death rates (aOR 1.536, 95% CI 1.011-2.628). DM was a contributing factor for culture-positive rates at the end of the second month and treatment failure and death of PTB patients, thus playing an unfavorable role in treatment effects of PTB.

A self-contrast approach to evaluate the inhibitory effect of chrysosplenetin, in the absence and presence of artemisinin, on the in vivo P-glycoprotein-mediated digoxin transport activity.

In this study, we used a self-contrast method, which excluded the individual difference, to evaluate the inhibitory effect of chrysosplentin (CHR) in the presence or absence of artemisinin (ART) on the P-glycoprotein (P-gp) transport activity. A sensitive and rapid UHPLC-MS/MS method was applied for quantification of digoxin, a P-gp-specific substrate, in rat plasma. A pharmacokinetic study was carried out: first after an oral administration of digoxin at a dose of 0.09 mg/kg (first period), followed by a 20-day wash-out, then after another administration of digoxin (second period). During the second period, test compounds were orally given three times per day for seven consecutive days. Results showed that the t1/2 of digoxin in all the groups had no significant difference between the first and second periods. The AUC0-24 , Cmax , tmax , and Clz /F of the negative control and ART alone groups showed no difference. However, the AUC0-24 and Cmax in the CHR alone, CHR-ART (1:2) and verapamil (positive control) groups showed 2.34-, 3.04-, 1.79-, and 1.81-, 1.99-, 2.06-fold increases along with 3.50-, 3.84- and 4.76-fold decreases for CLz /F, respectively. The tmax in the CHR-ART (1:2) group increased 3.73-fold. In conclusion, our self-contrast study suggested that CHR, especially when combined with ART in a ratio of 1:2, inhibited P-gp activity while ART alone has no effect. Copyright © 2016 John Wiley & Sons, Ltd.

Risk of Treatment Failure in Patients with Drug-susceptible Pulmonary Tuberculosis in China.

The objective of this prospective study of the risks of treatment failure in patients with drug-susceptible pulmonary tuberculosis (PTB) was to provide reference data to help develop a disease control strategy. Participants were recruited in eight provinces of China from October 2008 to December 2010. A total of 1447 patients with drug-susceptible PTB and older than 15 years of age were enrolled. Demographic characteristics, bacteriological test results, and patient outcome, i.e., cure or treatment failure were recorded and compared using the chi-square or Fisher's exact tests. Multivariate logistic regression was used to identify factors associated with risk of treatment failure. Of the 1447 patients who were enrolled, 1349 patients (93.2%) were successfully treated and 98 (6.8%) failed treatment. Failure was significantly associated with age 365 years [odds ratio (OR)=2.522, 95% confidence interval (CI): (1.097-5.801)], retreatment [OR=2.365, 95% CI: (1.276-4.381)], missed medicine [OR=1.836, 95% CI: (1.020-3.306)], treatment not observed [OR=1.879 95% CI: (1.105-3.195)], and positive culture result after the first [OR=1.971, 95% CI: (1.080-3.597)] and second month [OR=4.659, 95% CI: (2.590-8.382)]. The risk factors associated with treatment failure were age 365 years, retreatment, missed medication, treatment not observed, and positive culture at the end of month 1 or month 2. These risk factors should be monitored during treatment and interventions carried out to reduce or prevent treatment failure and optimize treatment success.

Quantitative Analysis of the Migration and Accumulation of Bacillus subtilis in Asparagus officinalis.

Bacillus subtilis B96-II is a broad-spectrum biological control strain. It effectively suppresses soil-borne fungal diseases in vegetables. A green fluorescence protein (GFP) was expressed in B96-II to detect migration of B96-II into the root and stem of asparagus. The GFP-tagged B96-II (B96-II-GFP) strain exhibited bright green fluorescence under a fluorescence microscope. GFP was stable and had no apparent effects on the growth of the strain. Asparagus plants were planted in the soil inoculated with B96-II-GFP. Our results showed that B96-II-GFP was detected in both the root and stem 15, 30, and 45 days after the asparagus seedlings were planted. B96-II-GFP was also detected in leaves but at a lower concentration. The highest concentration was detected in 15 days, and the number of bacteria decreased subsequently irrespective of duration of growth or sampling period. The highest concentration of B96-II-GFP was present in the root base suggesting that the root base served as the hub of bacterial migration from the soil to the stem.

Biodosimetry Based on Gamma-H2AX Quantification in Human Peripheral Blood Lymphocytes after Partial-body Irradiation.

ABSTRACT: Quantification of gamma-H2AX foci can estimate exposure to ionizing radiation. Most nuclear and radiation accidents are partial-body irradiation, and the doses estimated using the total-body irradiation dose estimation formula are often lower than the actual dose. To evaluate the dose-response relation of gamma-H2AX foci in human peripheral blood lymphocytes after partial-body irradiation and establish a simple and high throughput model to estimate partial-body irradiation dose, we collected human peripheral blood and irradiated with 0-, 0.5-, 1-, 2-, 3-, 4-, 5-, 6-, and 8-Gy gamma rays to simulate total-body irradiation in vitro. Gamma-H2AX foci were quantitated by flow cytometry at 1 h after irradiation, and a dose-response curve was established for total-body irradiation dose estimation. Then, a partial-body irradiation dose-response calibration curve was established by adding calibration coefficients based on the Dolphin method. To reflect the data distribution of all doses more realistically, the partial-body irradiation dose-response calibration curve was divided into two sections. In addition, partial-body irradiation was simulated in vitro, and the PBI data were substituted into curves to verify the accuracy of the two partial-body irradiation calibration curves. Results showed that the dose estimation variations were all less than 30% except the 25% partial-body irradiation group at 1 Gy, and the partial-body irradiation calibration dose-response curves were YF 1 = - 3.444 x 2 + 18.532 x + 3.109, R 2 = 0.92 (YF ≤ 27.95); YF 2 = - 2.704 x 2 + 37.97 x - 56.45, R 2 = 0.86 (YF > 27.95). Results also suggested that the partial-body irradiation dose-response calibration curve based on the gamma-H2AX foci quantification in human peripheral blood lymphocytes is a simple and high throughput model to assess partial-body irradiation dose.

Multiple exposures to low-dose ionizing radiation induced the initiation and progression of pro-atherosclerotic phenotypes in mice and vascular endothelial cell damage.

OBJECTIVE: This study aimed to investigate the effects of low-dose radiation on the abdominal aorta of mice and vascular endothelial cells. METHODS: Wild-type and tumor-bearing mice were exposed to 15 sessions of low-dose irradiation, resulting in cumulative radiation doses of 187.5, 375, and 750 mGy. The effect on the cardiovascular system was assessed. Immunohistochemistry analyzed protein expressions of PAPP-A, CD62, P65, and COX-2 in the abdominal aorta. Microarray technology, Gene Ontology analysis, and pathway enrichment analysis evaluated gene expression changes in endothelial cells exposed to 375 mGy X-ray. Cell viability was assessed using the Cell Counting Kit 8 assay. Immunofluorescence staining measured γ-H2AX levels, and real-time polymerase chain reaction quantified mRNA levels of interleukin-6 (IL-6), ICAM-1, and Cx43. RESULTS: Hematoxylin and eosin staining revealed thickening of the inner membranes and irregular arrangement of smooth muscle cells in the media membrane at 375 and 750 mGy. Inflammation was observed in the inner membranes at 750 mGy, with a clear inflammatory response in the hearts of tumor-bearing mice. Immunohistochemistry indicated increased levels of PAPP-A, P65, and COX-2 post-irradiation. Microarray analysis showed 425 up-regulated and 235 down-regulated genes, associated with processes like endothelial cell-cell adhesion, IL-6, and NF-κB signaling. Cell Counting Kit 8 assay results indicated inhibited viability at 750 mGy in EA.hy926 cells. Immunofluorescence staining demonstrated a dose-dependent increase in γ-H2AX foci. Reverse transcription quantitative PCR results showed increased expression of IL6, ICAM-1, and Cx43 in EA.hy926 cells post 750 mGy X-ray exposure. CONCLUSION: Repeated low-dose ionizing radiation exposures triggered the development of pro-atherosclerotic phenotypes in mice and damage to vascular endothelial cells.

Major vault protein promotes locomotor recovery and regeneration after spinal cord injury in adult zebrafish.

In contrast to mammals, adult zebrafish recover locomotor functions after spinal cord injury (SCI), in part due to axonal regrowth and regeneration permissivity of the central nervous system. Upregulation of major vault protein (MVP) expression after spinal cord injury in the brainstem of the adult zebrafish prompted us to probe for its contribution to recovery after SCI. MVP is a multifunctional protein expressed not only in many types of tumours but also in the nervous system, where its importance for regeneration is, however, unclear. Using an established zebrafish SCI model, we found that MVP mRNA and protein expression levels were increased in ependymal cells in the spinal cord caudal to the lesion site at 6 and 11 days after SCI. Double immunolabelling showed that MVP was co-localised with Islet-1 or tyrosine hydroxylase around the central canal of the spinal cord in sham-injured control fish and injured fish 11 days after surgery. MVP co-localised with the neural stem cell marker nestin in ependymal cells after injury. By using an in vivo morpholino-based knock-down approach, we found that the distance moved by MVP morpholino-treated fish was reduced at 4, 5 and 6 weeks after SCI when compared to fish treated with standard control morpholino. Knock-down of MVP resulted in reduced regrowth of axons from brainstem neurons into the spinal cord caudal to the lesion site. These results indicate that MVP supports locomotor recovery and axonal regrowth after SCI in adult zebrafish.

Pregabalin induced balance disorder, asthenia, edema, and constipation in an elderly adult: A case report.

BACKGROUND: Pregabalin is widely used to treat neuropathic pain associated with postherpetic neuralgia. To our knowledge, this is the first report on simultaneously occurring dose-related adverse drug reactions (ADRs) of balance disorder, asthenia, peripheral edema, and constipation in an elderly patient after pregabalin. CASE SUMMARY: A 76-year-old female with a history of postherpetic neuralgia was prescribed pregabalin (300 mg daily). After taking pregabalin for 7 d, the patient developed balance disorder, weakness, peripheral pitting edema (2+), and constipation. On days 8-14, the pregabalin dose was reduced to 150 mg/d based on creatinine clearance. The patient's peripheral edema improved significantly with the disappearance of all other adverse symptoms. On day 15, the pregabalin dose was increased to 225 mg/d to relieve pain. Unfortunately, the symptoms mentioned earlier gradually reappeared after 1 wk of pregabalin treatment. However, the complaints were not as severe as when taking 300 mg/d pregabalin. The patient consulted her pharmacist by telephone and was advised to reduce the dose of pregabalin to 150 mg/d and add acetaminophen (0.5 g, q6h) to relieve pain. The patient's ADRs gradually improved over the following week. CONCLUSION: Older patients should be prescribed a lower initial dose of pregabalin. The dose should be titrated to the maximum tolerable dose to avoid dose-limiting ADR. Dose reduction and the addition of acetaminophen may help limit ADR and improve pain control.

Melatonin inhibits senescence-associated melanin pigmentation through the p53-TYR pathway in human primary melanocytes and the skin of C57BL/6 J mice after UVB irradiation.

UVB exposure accelerates skin aging and pigmentation. Melatonin effectively regulates tyrosinase (TYR) activity and aging. The purpose of this study was to determine the association between premature senescence and pigmentation, and the mechanism of melanin synthesis effected by melatonin. Primary melanocytes were extracted and identified from the male foreskin. To inhibit TYR expression, primary melanocytes were transduced with the lentivirus pLKD-CMV-EGFP-2A-Puro-U6-TYR. The wild-type TYR(+/+) and TYR(-/-) or TYR(+/-) knockout C57BL/6 J mice were used to determine the role of TYR on melanin synthesis in vivo. Results showed that UVB-induced melanin synthesis is dependent on TYR in primary melanocytes and mice. Furthermore, in primary melanocytes pretreated with Nutlin-3 or PFT-α to up or downregulate p53, results showed that premature senescence and melanin synthesis increased in primary melanocytes after UVB irradiation at 80 mJ/cm2, and further increased after being treated with Nutlin-3, while significantly decreased with PFT-α. In addition, melatonin inhibited UVB-induced premature senescence associated with inactivation of p53 and phosphorylation of p53 on Ser15 (ser-15), a decrease of melanin synthesis accompanied by reduced TYR expression. Moreover, skin erythema and pigmentation induced by UVB were reduced in the dorsal and ear skin of mice topically pretreated with 2.5% melatonin. These indicate that melatonin inhibits UVB-induced senescence-associated pigmentation via the p53-TYR pathway in primary melanocytes and prevents pigmentation obviously in the dorsal and ear skin of C57BL/6 J mice after UVB irradiation. KEY MESSAGES: P53 links UVB irradiation-induced senescence and senescence-associated pigmentation and regulates TYR in primary melanocytes after UVB irradiation. Melatonin inhibits senescence-associated pigmentation through the p53-TYR pathway in primary melanocytes. Melatonin prevents skin erythema and melanin pigmentation induced by UVB irradiation in the dorsal and ear skin of C57BL/6J mice.

Case Report: Community-Acquired Burkholderia cepacia Pneumonia of a Patient with Pulmonary Tuberculosis.

Community-acquired Burkholderia cepacia pneumonia is rare. We report a 29-year-old female who suffered pulmonary tuberculosis and developed community-acquired Burkholderia cepacia pneumonia, which was confirmed by the culture of the pulmonary tissue. The patient received antitubercular therapy. Meanwhile, she was treated with meropenem and minocycline. The patient was followed up for 6 months, and she achieved complete absorption of lung lesions.

Emphysematous pyelonephritis: Six case reports and review of literature.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a severe acute necrotizing infection of the renal parenchyma and surrounding tissues that causes the presence of gas in the renal parenchyma, collecting system, or perinephric tissue and has a poor prognosis. EPN occurs primarily in people with diabetes mellitus (DM), but can occur in those without DM when the associated renoureteral unit is obstructed. CASE SUMMARY: We describe our experience with six patients who developed EPN. Five patients had DM, including one with diabetic ketoacidosis, one with multisystem involvements, including eye, lung and brain. Bilateral urolithiasis was present in one case, along with emphysematous cystitis. Unilateral kidney stones were present in one patient. One patient was an older man in poor general health. Five individuals survived and underwent surgical procedures including ureteral stent installation (Double J stent placement), percutaneous nephrostomy and perinephric abscess puncture drainage, while one died because the patient's family chose to terminate therapy. Klebsiella pneumoniae and Escherichia coli were the microorganisms implicated. CONCLUSION: We conclude that EPN is a potentially fatal illness. A positive outcome necessitates early detection. Therapeutic measures should be implemented as soon as a diagnosis is made.

Diabetic Ketoacidosis With Acute Pancreatitis in Patients With Type 2 Diabetes in the Emergency Department: A Retrospective Study.

Objective: This study aims to explore the incidence and clinical features of acute pancreatitis (AP) in patients with type 2 diabetes diabetic ketoacidosis (DKA) in the emergency department and discuss the predictive value of some pathological indicators for AP in DKA. Methods: Inpatient medical data of DKA patients hospitalized to our hospital's emergency department between January 2017 and January 2021 were evaluated retrospectively. These DKA patients were split into two groups based on whether they had AP or not. We examined the two groups' epidemiologic features, baseline laboratory results, and clinical outcomes. The Bedside Index for Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), and Logistic Organ Failure System (LODS) scores were computed and compared across groups. Results: The prevalence of AP in DKA patients was 15.53%. The difference in Abdominal pain between the two groups of patients was statistically significant (p < 0.001), and there was no statistical difference in age, gender, and BMI. The DKA and AP group LOS (P < 0.001), ICU admission rate (P = 0.046), anion gap (P < 0.001), red blood cell (P = 0.002), hemoglobin (P < 0.001), hematocrit (P = 0.002), serum triglyceride (P < 0.001), serum cholesterol (P < 0.001), serum amylase (P = 0.004), random glucose (P = 0.028), plasma fibrinogen (P < 0.001), glycosylated hemoglobin [HbA1c (%); P = 0.008] higher than the DKA group, pH (P < 0.001), carbon dioxide combining power (CO2CP; P < 0.001), ionized calcium (Ca2+; P = 0.022), ionized sodium (Na+; P = 0.001), and correction Na (P = 0.034) lower than the DKA group. Multivariate analysis showed that low pH (P < 0.05), hypertriglyceridemia (P = 0.001), and hypercholesterolemia (P = 0.01) were risk factors for DKA combined with AP. ROC curve analysis showed that the three cut-off value: serum triglycerides of 10.52 mmol/L, serum cholesterol of 9.03 mmol/L, and pH of 7.214. Serum triglyceride has the largest area under the curve (0.93). Under this cut-off value, the sensitivity (80%) and specificity of serum triglyceride, the degree (93.7%) is the highest, while the positive predictive value (62.0%) and negative predictive value (94.7%) of serum cholesterol are the highest. Conclusions: A severe episode of DKA with significant acidosis and hyperlipidemia is more likely to be linked with AP. The frequently used critical illness score is ineffective in determining the severity of the condition. When the serum triglyceride cut-off value is 10.52mmol/L, it has a higher predicted value for AP in DKA.

Chemical Shift-Encoded MRI of Bone Metabolic Markers in Ankylosing Spondylitis.

Objective: To investigate the feasibility and correlation of sacroiliac joint (SIJ) fat fraction (FF) and R2∗ as markers of bone metabolism in patients with ankylosing spondylitis (AS). Methods: 75 AS patients were classified into an early active group (EA), late active group (LA), and inactive group (IA). Additionally, 54 matched healthy individuals were selected to be part of the normal control group (NC). All participants underwent chemical shift encoded based MRI (IDEAL-IQ) and routine clinical SIJ MRI at 3.0 T. FF and R2∗ were measured in subchondral bone, bone marrow edema (BME), and fat metaplasia (FM). Out of the participants, 39 with BME lesions (15 from EA, 16 from LA, 8 from IA) and 39 with FM lesions (9 from EA, 17 from LA, 13 from IA) were included. Differences in FF, R2∗ value for subchondral bone of all participants and for BME, FM lesions were evaluated. Subsequently, different stages of BME and FM in patient groups were compared, and the relationship between FF and R2∗ was analyzed. Results: A significant difference in FF was demonstrated among the BME, FM and the normal bone marrow (p < 0.001), meanwhile, the difference of R2∗ value in FM was significantly lower (p = 0.034, 0.012) than that of BME and that of normal bone marrow. At lever of different lesions, only the FF for BME was significantly different among 3 patient groups (p = 0.001), while there was no significantly different FF for FM among 3 patient groups. Unlike in BME lesions, the FF in FM lesions had a negative correlation with R2∗ (p < 0.001, r = -0.488). Conclusion: FF and R2∗ measurements help to quantitatively analyze the bone marrow fat composition and bony trabecular microstructure changes in AS, providing a noninvasive and accurate assessment basis for AS bone metabolism abnormalities.

Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro.

Objective: To evaluate the clinical efficacy and safety of baricitinib, a Janus kinase (JAK) inhibitor, in treating patient with progressing vitiligo, and to further explore the regulation of baricitinib on melanocytes (MCs) in vitro. Methods: Four patients with progressing vitiligo were treated with oral baricitinib for a total of 12 weeks. MCs were cultured in vitro and irradiated by high-dose ultraviolet B (UVB, 150mJ/cm2) to make an MC damaged model (MC-Ds). Baricitinib was added at a final concentration of 25 µM. Dopamine staining and NaOH method were used to measure the tyrosinase activity and melanin level, respectively, real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1). Results: Significant re-pigmentation was observed in the week 12 without obvious side effects. Depigmentation occurred in 2 patients at the 3-month follow-up. Laboratory research found that higher doses of UVB irradiation (150mJ/cm2) could decrease melanin content of MCs, baricitinib (25 µM) could significantly promote tyrosinase activity, melanin content, and TYR, TRP-1 gene expression of MC-Ds. Conclusion: Our preliminary study showed that baricitinib was effective and safe in treating progressing vitiligo. Baricitinib could promote tyrosinase activity, melanin content and TYR, TRP1 gene expression of MC-Ds in vitro.

Effect of Ultraviolet B Irradiation on Melanin Content Accompanied by the Activation of p62/GATA4-Mediated Premature Senescence in HaCaT Cells.

OBJECTIVE: To explore the effect and mechanism of ultraviolet B (UVB) on melanin synthesis and premature senescence in human immortalized keratinocytes (HaCaT) cells. METHODS: HaCaT cells were irradiated with 0, 20, 50, 80, 100, 150, and 200 mJ/cm2 of UVB. NaOH method was used for melanin content assay, cellular tyrosinase (TYR) activity was determined by 3,4-Dihydroxy-L-phenylalanine (L-DOPA) oxidation to dopachrome, premature senescence was analyzed by senescence-associated beta-galactosidase (SA-ß-gal) staining kit, and the levels of p21, p16, p62, and GATA4 proteins were detected by Western blotting. Premature senescence was inhibited by the inhibitors of ataxia telangiectasia mutated (ATM) or ataxia telangiectasia and Rad3-related (ATR), and the p53 signaling pathway was activated by Nutlin-3. The mRNA levels of senescence-associated secretory phenotype (SASP) factors including tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor A (VEGF-A), and interleukin-8 (IL-8) were measured by real-time quantitative polymerase chain reaction in HaCaT cells after 80 mJ/cm2 of UVB irradiation. RESULTS: The melanin level increased significantly with the elevation of irradiation dose (F = 28.19, 43.82, 143.60, P < .05), reaching the peak at the dose of 80 mJ/cm2. The tyrosinase activity increased significantly (F = 84.50, P < .05), the percentage of premature senescence increased (F = 16.31, P < .05), the levels of p62 decreased, and the level of GATA4 increased obviously with the increase of UVB dose after irradiation. The UVB-induced promotion of GATA4 level was significantly inhibited by being treated with ATM or ATR inhibitor. However, this did not occur in the Nutlin-3-treated group. The mRNA and protein expression of TNF-α increased significantly at 72 h at 80 mJ/cm2 of UVB irradiation. CONCLUSIONS: Melanin contents increased first and decreased afterward with the increasing of UVB irradiation. The decrease of p62-mediated selective autophagy was accompanied by the accumulation of GATA4 after different doses of UVB irradiation. Activation of this p62/GATA4 pathway depends on the ATM and ATR but is independent of p53, and the SASP factor was activated in HaCaT cells at 80 mJ/cm2 of UVB irradiation.