Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

Hypothyroidism's effect on stroke limited to specific subtypes: A Mendelian randomization study.

BACKGROUND: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes. RESULTS: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant. CONCLUSION: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS.

Causal Association between Tea Intake and Acute Cerebrovascular Events: A Multivariate Mendelian Randomized Study in European Populations.

BACKGROUND: Numerous research works have investigated the association between tea consumption and the risk of acute cerebrovascular events; however, the results are inconsistent. OBJECTIVES: We used Mendelian randomization (MR) to evaluate the causal association between tea intake and several acute cerebrovascular events, including any ischemic stroke, large atherosclerotic stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), intracranial hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS: We obtained summary genome-wide association study (GWAS) data on tea intake and acute cerebrovascular events in populations of European ancestry. The GWAS on tea intake is derived from the UK Biobank, where we have chosen single-nucleotide polymorphisms (SNPs) closely associated with it as instrumental variables. We also obtained summary data on ischemic stroke from a GWAS meta-analysis, as well as summary data on ICH and SAH from the FinnGen study. We first explored the causal association between tea intake and several acute cerebrovascular events using univariate Mendelian randomization (UVMR), and then further assessed the causal association between tea intake and SVS using multivariate Mendelian randomization (MVMR) corrected for multiple confounders. RESULTS: In UVMR, genetically predicted increases in tea intake were linked to a lower risk of SVS (OR: 0.58; 95% CI: 0.39, 0.86). There was no causal association between tea intake and the risk of other acute cerebrovascular events. In the MVMR, our results show that there was still a significant causal association between drinking tea and SVS, after adjusting body mass index, total cholesterol, low-density lipoprotein cholesterol, diabetes, hypertension, smoking, and alcohol consumption. CONCLUSION: This MR study provides new genetic evidence that increased tea intake reduces the risk of SVS in the European population. However, possibly because of limited statistical power, the study did not find that tea consumption reduced the risk of several other acute cerebrovascular events.

Causal relationship between rheumatoid arthritis and hypothyroidism or hyperthyroidism: a bidirectional two-sample univariable and multivariable Mendelian randomization study.

Objective: The causal relationship between Rheumatoid arthritis (RA) and hypothyroidism/hyperthyroidism remains controversial due to the limitations of conventional observational research, such as confounding variables and reverse causality. We aimed to examine the potential causal relationship between RA and hypothyroidism/hyperthyroidism using Mendelian randomization (MR). Method: We conducted a bidirectional two-sample univariable analysis to investigate the potential causal relationship between hypothyroidism/hyperthyroidism and RA. Furthermore, we performed a multivariate analysis to account for the impact of body mass index (BMI), smoking quantity, and alcohol intake frequency. Results: The univariable analysis indicated that RA has a causative influence on hypothyroidism (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.01-1.14, P=0.02) and hyperthyroidism (OR=1.32, 95% CI=1.15-1.52, P<0.001). When hypothyroidism/hyperthyroidism was considered as an exposure variable, we only observed a causal relationship between hypothyroidism (OR=1.21, 95% CI=1.05-1.40, P=0.01) and RA, whereas no such connection was found between hyperthyroidism (OR=0.91, 95% CI=0.83-1.01, P=0.07) and RA. In the multivariate MR analyses, after separately and jointly adjusting for the effects of daily smoking quantity, alcohol intake frequency, and BMI, the causal impact of RA on hypothyroidism/hyperthyroidism and hypothyroidism on RA remained robust. However, there is no evidence to suggest a causal effect of hyperthyroidism on the risk of RA (P >0.05). Conclusion: Univariate and multivariate MR analyses have validated the causal association between RA and hypothyroidism/hyperthyroidism. Hypothyroidism confirmed a causal relationship with RA when employed as an exposure variable, whereas no such relationship was found between hyperthyroidism and RA.

Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients.

BACKGROUND: Tenofovir alafenamide (TAF) has a serum lipid-raising effect in patients with HIV; however, its effect on serum lipids and nonalcoholic fatty liver disease (NAFLD) risk in patients with chronic hepatitis B (CHB) is unclear. AIM: To compare the effects of TAF and entecavir (ETV) on serum lipid levels in patients with CHB. METHODS: In this retrospective cohort study, the data including the clinical features, serum lipids, and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed. We used propensity score-matched models to assess the effects on high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol (TCHO). RESULTS: A total of 336 patients (75.60% male) were included; 63.69% received TAF and 36.31% received ETV. Compared with the ETV group, the TAF group had significantly higher TCHO levels after treatment (4.67 ± 0.90 vs 4.36 ± 1.05, P = 0.006). In a propensity score-matched model for body mass index, age, sex, smoking, drinking, presence of comorbidities such as NAFLD, cirrhosis, diabetes mellitus, and hypertension, TAF-treated patients had significantly increased TCHO levels compared to that at baseline (P = 0.019). There was no difference for the ETV group. Body mass index, sex, hypertension, baseline TCHO, and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis. However, 1-year TAF treatment did not increase the incidence of NAFLD. CONCLUSION: A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV. However, TAF-induced dyslipidemia did not increase the incidence of NAFLD.

The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian randomization study.

Objective: Investigating the association between inflammatory cytokines and hypothyroidism remains challenging due to limitations in traditional observational studies. In this study, we employed Mendelian randomization (MR) to assess the causal relationship between 41 inflammatory cytokines and hypothyroidism. Method: Inflammatory cytokines in 30,155 individuals of European ancestry with hypothyroidism and in a GWAS summary containing 8,293 healthy participants were included in the study for bidirectional two-sample MR analysis. We utilized inverse variance weighting (IVW), weighted median (WM), and Mendelian randomization-Egger (MR-Egger) methods. Multiple sensitivity analyses, including MR-Egger intercept test, leave-one-out analysis, funnel plot, scatterplot, and MR-PRESSO, were applied to evaluate assumptions. Results: We found evidence of a causal effect of IL-7 and macrophage inflammatory protein-1ß (MIP-1ß) on the risk of hypothyroidism, and a causal effect of hypothyroidism on several cytokines, including granulocyte colony-stimulating factor (G-CSF), IL-13, IL-16, IL-2rα, IL-6, IL-7, IL-9, interferon-γ-inducible protein 10 (IP10), monokine induced by interferon (IFN)-γ (MIG), macrophage inflammatory protein-1ß (MIP-1ß), stem cell growth factors-ß (SCGF-ß), stromal cell derived factor-1α (SDF-1α), and tumor necrosis factor-α (TNF-α). Conclusion: Our study suggests that IL-7 and MIP-1ß may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications. However, further experimental studies are needed to validate the causal relationships and the potential of these cytokines as drug targets.

Have one's view of the important overshadowed by the trivial: chronic progressive external ophthalmoplegia combined with unilateral facial nerve injury: a case report and literature review.

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial encephalomyopathy that is characterized by progressive ptosis and impaired ocular motility. Owing to its nonspecific clinical manifestations, CPEO is often misdiagnosed as other conditions. Herein, we present the case of a 34-year-old woman who primarily presented with incomplete left eyelid closure and limited bilateral eye movements. During the 6-year disease course, she was diagnosed with myasthenia gravis and cranial polyneuritis. Finally, skeletal muscle tissue biopsy confirmed the diagnosis. Biopsy revealed pathological changes in mitochondrial myopathy. Furthermore, mitochondrial gene testing of the skeletal muscle revealed a single chrmM:8469-13447 deletion. In addition, we summarized the findings of 26 patients with CPEO/Kearns-Sayre syndrome who were misdiagnosed with other diseases owing to ocular symptoms. In conclusion, we reported a rare clinical case and emphasized the symptomatic diversity of CPEO. Furthermore, we provided a brief review of the diagnosis and differential diagnosis of the disease.

Clinical value of predictive models based on liver stiffness measurement in predicting liver reserve function of compensated chronic liver disease.

BACKGROUND: Assessment of liver reserve function (LRF) is essential for predicting the prognosis of patients with chronic liver disease (CLD) and determines the extent of liver resection in patients with hepatocellular carcinoma. AIM: To establish noninvasive models for LRF assessment based on liver stiffness measurement (LSM) and to evaluate their clinical performance. METHODS: A total of 360 patients with compensated CLD were retrospectively analyzed as the training cohort. The new predictive models were established through logistic regression analysis and were validated internally in a prospective cohort (132 patients). RESULTS: Our study defined indocyanine green retention rate at 15 min (ICGR15) ≥ 10% as mildly impaired LRF and ICGR15 ≥ 20% as severely impaired LRF. We constructed predictive models of LRF, named the mLPaM and sLPaM, which involved only LSM, prothrombin time international normalized ratio to albumin ratio (PTAR), age and model for end-stage liver disease (MELD). The area under the curve of the mLPaM model (0.855, 0.872, respectively) and sLPaM model (0.869, 0.876, respectively) were higher than that of the methods for MELD, albumin-bilirubin grade and PTAR in the two cohorts, and their sensitivity and negative predictive value were the highest among these methods in the training cohort. In addition, the new models showed good sensitivity and accuracy for the diagnosis of LRF impairment in the validation cohort. CONCLUSION: The new models had a good predictive performance for LRF and could replace the indocyanine green (ICG) clearance test, especially in patients who are unable to undergo ICG testing.

An Emerging Role of Proanthocyanidins on Psoriasis: Evidence from a Psoriasis-Like Mouse Model.

Background: Psoriasis is an immune-mediated, chronic inflammatory disease, and genetic, immune, oxidative stress (OS), and environmental factors are all thought to contribute to its occurrence. Proanthocyanidins (PCs) are natural flavonoids consisting of catechins and epicatechins which have anti-inflammatory and anti-OS activities. PCs have been widely used to treat various diseases, but reports regarding psoriasis are rare. Objective: To investigate the therapeutic effect and potential mechanisms of action of PCs in a psoriasis-like mouse model. Methods: Thirty male BALB/c hairless mice were assigned to six groups (n = 5): normal, model, low-dose PCs, medium-dose PCs, high-dose PCs, and control groups. The final five groups were dorsally exposed to 5% imiquimod (IMQ) cream once a day for 6 consecutive days, while the normal group received no intervention. Following the first day of IMQ application, mice in the PC-treated group were dosed with different amounts of PCs daily by oral gavage for six days, whereas mice in the control group received normal saline in the same way. One week later, skin lesions were evaluated by the severity of scoring system based on psoriasis area and severity index (PASI), and pathological alterations were assessed by hematoxylin-eosin (HE) staining. Indicators of inflammation or OS, such as interleukin- (IL-) 17, IL-23, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), and heme oxygenase-1 (HO-1), were determined by ELISA, RT-PCR, western blot, and immunohistochemistry (IHC) analysis. Results: IMQ administration induced the formation of large dark red plaques with thickly layered scales on the dorsal skin of mice; nevertheless, the lesions were substantially alleviated by PC administration. Histopathological alterations were observed in both model and control groups with epidermal hyperkeratosis, granulosa layer thinning, acanthosis, downward extension of rete ridges, dermal papillae expansion, capillary hyperplasia, and infiltration by inflammatory cells around blood vessels. These pathological changes, however, were restored by a range of doses of PCs, high-dose PCs in particular. Different doses of PCs significantly lowered the spleen index, levels of inflammatory or oxidative proteins (IL-17, IL-23, MDA, ROS, p-PI3K, and p-STAT3), and the mRNA expression of Il-17, Il-23, Vegf, and iNos. Protein and mRNA levels of anti-OS and anti-inflammatory biomarkers, including SOD, CAT, GSH, and HO-1, greatly increased after PC treatment, especially at the highest dose. Conclusions: Our findings reveal that PCs ameliorate psoriasis-like symptoms, suppressing the inflammatory response and mitigating OS damage in an IMQ-induced psoriasis-like mouse model. These effects are probably related to the inactivation of STAT3 and PI3K and activation of HO-1 signaling.

Postoperative Ileus with the Topical Application of Tongfu Decoction Based on Network Pharmacology and Experimental Validation.

Objective: Postoperative gastrointestinal dysfunction is a common and important complication of surgery. This study aimed to explore the key pharmacological mechanisms of Tongfu decoction in treating postoperative ileus (POI). Methods: The active ingredients of Tongfu decoction and their targets were screened using the TCMSP database and STITCH and SwissTargetPrediction databases, respectively. The GeneCards and DisGeNET databases were used to obtain POI dysfunction-related therapeutic targets. After screening, a drug-active-ingredient-therapeutic target network was constructed and the key target functional enrichment analysis was carried out. The Sprague-Dawley rats with POI were used for in vivo experimental verification. The serum levels of IL-1ß, IL-6, IL-10, IFN-γ, and MCP-1 were measured after surgery using enzyme-linked immunosorbent assay. The Western blot analysis was used to determine the expression of key proteins of the PI3K-Akt signaling pathway in colon tissues. Results: An interaction network was constructed containing 7 Chinese medicine components, 36 compounds, and 85 target proteins. The functional enrichment analysis showed that the target proteins mainly acted on the POI through the PI3K-Akt signaling pathway. In in vivo experiments, Tongfu decoction had a promoting effect on the serum level of IL-10, an inhibitory effect on the serum levels of IL-1ß and CCL2, and an inhibitory effect on the local expression of PI3K, pAkt, and mTOR in colon tissue. In addition, the Tongfu decoction increased the intestinal ink advancing rate. Conclusion: Nonoral Tongfu decoction can also be used to treat POI; its mechanism is affected by IL-10 and IL-1ß.The inhibition of the PI3K-Akt signaling pathway affected the treatment with Tongfu decoction by inducing an immune-inflammatory storm in POI.

Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERß and oxytocin of C57BL/6J female mice.

Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E2), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors ß immunoreactive neurons (ERß-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there's increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E2 levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERß-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E2. ERß/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions.

Treatment Effect of Mammary Duct Exploration Combined with Focal Resection on Granulomatous Lobular Mastitis.

OBJECTIVE: This study aims to summarize the treatment of granulomatous lobular mastitis with a low recurrence rate and high satisfaction rate. METHODS: In this study, the epidemiology and treatment effect was analyzed based on the general data and treatment effects. Patients treated for granulomatous lobular mastitis at the Dongzhimen Hospital, Beijing University of Chinese Medicine, and Beijing Contemporary Hospital from October 24, 2016, to May 8, 2019, were selected as subjects for the study. RESULTS: The results revealed that the common features of granulomatous lobular mastitis were nipple retraction, history of induced abortion, nipple discharge, history of thyroid disease, history of lactation mastitis, and mental illness. The cure rate of the disease was 100%, the recurrence rate was 0.38%, and the patient satisfaction rate was 97.71%. CONCLUSION: The combination of mammary duct exploration and focal resection has a positive effect on the treatment of this disease and is worthy of clinical popularization.

A retrospective study on 221 patients with granulomatous lobular mastitis treated by a combination of traditional Chinese medicine and western medicine.

OBJECTIVE: This study aims to investigate the clinical efficacy and safety of integrative Chinese and Western medicine in the treatment of granulomatous lobular mastitis. METHODS: In the present study, the clinical data of patients with granulomatous lobular mastitis in our hospital were retrospectively analyzed. According to the treatment regimens, these patients were divided into two groups: observation group (n=92) and control group (n=129). Patients in the observation group were treated with traditional Chinese medicine in combination with the surgical treatment of Western medicine, while the patents in the control group received surgical treatment alone. The main observation indexes included clinical cure rate, mass size, prolactin level and aesthetic evaluation results of the breasts. RESULTS: The results revealed that there was no significant correlation between the observation group and control group, in terms of age, prolactin level, and marriage and childbearing history (P>0.05). Furthermore, the recurrence rate was lower in the observation group, when compared to the control group, and the difference was statistically significant (P<0.05). The aesthetic evaluation was higher in the observation group than in the control group, and the difference was statistically significant (P<0.05). However, the difference in the transverse diameter and long diameter of the tumor and clinical cure rate was not statistically significant (P>0.05) between the observation group and control group. CONCLUSION: Compared with the simple surgical treatment of Western medicine, the combination of traditional Chinese medicine and Western medicine in the treatment of granulomatous lobular mastitis can significantly reduce the recurrence rate, and improve the symmetry and beauty of bilateral breasts, which is worthy of clinical application. KEY WORDS: Granulomatous lobular mastitis, Integrated Chinese and western medicine treatment, Unclog lacteal, Prolactin, Aesthetic evaluation of milk preservation.

Improvement of d-d interactions in density functional tight binding for transition metal ions with a ligand field model: assessment of a DFTB3+U model on nickel coordination compounds.

To improve the description of interactions among the localized d, f electrons in transition metals, we have introduced a ligand-field motivated contribution into the Density Functional Tight Binding (DFTB) model. Referred to as DFTB3+U, the approach treats the d, f electron repulsions with rotationally invariant orbital-orbital interactions and a Hartree-Fock model; this represents a major conceptual improvement over the original DFTB3 approach, which treats the d, f-shell interactions in a highly averaged fashion without orbital level of description. The DFTB3+U approach is tested using a series of nickel compounds that feature Ni(ii) and Ni(iii) oxidation states. By using parameters developed with the original DFTB3 Hamiltonian and empirical +U parameters (F0/2/4 Slater integrals), we observe that the DFTB3+U model indeed provides substantial improvements over the original DFTB3 model for a number of properties of the nickel compounds, including the population and spin polarization of the d-shell, nature of the frontier orbitals, ligand field splitting and the energy different between low and high spin states at OPBE optimized structures. This proof-of-concept study suggests that with self-consistent parameterization of the electronic and +U parameters, the DFTB3+U model can develop into a promising model that can be used to efficiently study reactive events involving transition metals ion condensed phase systems. The methodology can be integrated with other approximate QM methods as well, such as the extended tight binding (xTB) approach.

A clinical study on the treatment of granulomatous lobular mastitis by the external application of the internal pus-expelling decoction and operation.

BACKGROUND: The objective of this study was to evaluate the clinical efficacy of the external application of internal expulsion pus-expelling decoction (IEPED) combined with surgery in the treatment of granulomatous lobular mastitis (GLM). METHODS: A total of 110 patients in our hospital with sepsis GLM were randomly divided into two groups: treatment group (n=60, the wound was treated with IEPED) and control group (n=50, the wound was not treated with IEPED). We assessed the recurrence, contra lateral breast form, and aesthetic evaluation of the patients in the two groups. RESULTS: The total effective rates in the patients in the treatment group and the control group were 90% and 68%, respectively, after the preoperative pretreatment and before radical surgery (P<0.05). After 10 days of receiving the debridement treatment, the two groups were compared in term of physical signs scores and the difference was statistically significant (P<0.05). Within one year of the regular follow-up after treatment, 0 case recurred in the treatment group and 1 case recurred in the control group (P>0.05). In the treatment group, 30 cases showed excellent results in the aesthetic evaluation of breast appearance, 18 cases were good, and the overall excellent and good rate was up to 80%. In the control group, 12 cases showed excellent results and 16 cases showed good results, with the overall excellent and good rate reaching 56% (P<0.05). CONCLUSIONS: In patients with abscess debridement of GLM, the external application of IEPED can significantly reduce the primary lesion of patients with abscess GLM, reduce the surgical resection area, and maximize the preservation of the patients' breast appearance.

Prognostic role of ACTL10 in Cytogenetic Normal Acute Myeloid Leukemia.

ACTL10 is a member of the actin family; however, despite previous studies suggesting that certain proteins in this family may be related to the pathogenesis of leukemia, to the best of our knowledge, no studies to date have demonstrated any association between ACTAL10 and leukemia. Thus, the present study aimed to determine the association between ACTL10 expression levels, DNA methylation levels and the clinical prognosis in cytogenic normal acute myeloid leukemia (CN-AML). Data from seventy-five patients with CN-AML and patients with AML treated with chemotherapy or allogeneic hematopoietic stem cell transplantation were obtained from The Cancer Genome Atlas (TCGA) dataset and were used to analyze the clinical prognosis of ACTL10 RNA expression levels and DNA methylation levels. In addition, the study also investigated the combined clinical prognosis of ACTL10 RNA expression levels and ACTL10 DNA methylation levels in 74 patients with CN-AML from the TCGA dataset. ACTL10 RNA expression levels were observed to be highly expressed in patients with CD34+/CD38+ AML (P<0.01). Both ACTL10 RNA expression levels and DNA methylation were found to be independent prognostic factors for patients with CN-AML; patients with CN-AML in the ACTL10 RNA-high expression group had an increased EFS (P=0.0016) and OS (P=0.014) and patients in ACTL10 DNA methylation-low group also demonstrated a long EFS (P<0.0001) and OS (P=0.004). Notably, integrating ACTL10 RNA expression levels and ACTL10 DNA methylation levels could more accurately predict the prognosis of patients with CN-AML (EFS and OS, P<0.0001). In conclusion, the findings of the present study suggested that the high RNA expression levels and low DNA methylation levels of ACTL10 may predict a good prognosis in patients with CN-AML.

Clinical prognostic implications of EPB41L4A expression in multiple myeloma.

Background: Multiple myeloma (MM) is one of the most common incurable malignancies in malignant plasma cell disease. EPB41L4A is a target gene for the Wnt/ß-catenin pathway, which is closely related to the survival of multiple myeloma cells. However, there is currently no research report on the prognostic significance of the EPB41L4A gene in MM. Methods: We studied the biological significance and prognostic significance of EPB41L4A expression in MM by integrating 1956 MM samples from 7 datasets, and explored the relationship between EPB41L4A expression and MM ISS stage, molecular type, therapeutic response and survival. Results: We found that the expression level of EPB41L4A is inversely proportional to the copy number of 1q21 (P = 3.4e-13). EPB41L4A was low expressed in MAF, MMSET and proliferating molecular typing patients (P <= 0.001). High expression of EPB41L4A can predict good survival in MM (EFS: P < 0.0001; OS: P < 0.0001). We found that patients with relapsed MM had lower expression levels of EPB41L4A than those without recurrence (P = 0.0039). We also found that EPB41L4A can predict the prognosis of MM patients may be related to DNA replication. These results indicate that the initial expression level of EPB41L4A can predict the prognosis of MM patients. Conclusions: We found that the high expression of EPB41L4A predicts good survival level in MM.

Emerging Perspective: Role of Increased ROS and Redox Imbalance in Skin Carcinogenesis.

Strategies to battle malignant tumors have always been a dynamic research endeavour. Although various vehicles (e.g., chemotherapeutic therapy, radiotherapy, surgical resection, etc.) are used for skin cancer management, they mostly remain unsatisfactory due to the complex mechanism of carcinogenesis. Increasing evidence indicates that redox imbalance and aberrant reactive oxygen species (ROS) are closely implicated in the oncogenesis of skin cancer. When ROS production goes beyond their clearance, excessive or accumulated ROS could disrupt redox balance, induce oxidative stress, and activate the altered ROS signals. These would damage cellular DNA, proteins, and lipids, further leading to gene mutation, cell hyperproliferation, and fatal lesions in cells that contribute to carcinogenesis in the skin. It has been known that ROS-mediated skin carcinogenesis involves multiple ways, including modulating related signaling pathways, changing cell metabolism, and causing the instability of the genome and epigenome. Nevertheless, the exact role of ROS in skin cancer has not been thoroughly elucidated. In spite of ROS inducing skin carcinogenesis, toxic-dose ROS could trigger cell death/apoptosis and, therefore, may be an efficient therapeutic tool to battle skin cancer. Considering the dual role of ROS in the carcinogenesis and treatment of skin cancer, it would be essential to clarify the relationship between ROS and skin cancer. Thus, in this review, we get the related data together to seek the connection between ROS and skin carcinogenesis. Besides, strategies basing on ROS to fight skin cancer are discussed.

Composition and charge state influence on the ion-neutral collision cross sections of protonated N-linked glycopeptides: an experimental and theoretical deconstruction of coulombic repulsion vs. charge solvation effects.

Ion mobility spectrometry (IMS) is of significant interest as a platform for glycoanalysis. While much attention has been focused on the resolution of isomeric carbohydrates and glycoconjugates, another appealing aspect of IMS is the ability to sort different classes of biomolecules into distinct regions of mass vs. mobility space. This capability has potential to greatly simplify glycoproteomic analyses, as glycosylated and non-glycosylated peptides can be rapidly partitioned in the gas phase. Nevertheless, the physical and chemical characteristics of glycopeptides that dictate their mass vs. mobility loci have yet to be systematically investigated. This report presents an IMS study of model protonated glycopeptide ions with systematically varied oligosaccharide topologies, polypeptide sequences, and charge states. In all, over 110 ion-neutral collision cross sections (CCSs) were measured and analyzed in the context of the physicochemical characteristics of the analytes. Glycan size and composition emerged as a decisive factor in dictating the CCS space occupied by the glycopeptides and exerted this influence in a charge state dependent fashion. Furthermore, elongation of the glycan group was found to either increase or decrease glycopeptide CCSs depending on the ion charge state and the size of the glycan. Molecular dynamics (MD) simulations of the gas phase structures and CCSs of selected glycopeptides revealed that the experimental observations were consistent with a glycan size and charge state dependent interplay between destabilizing coulombic repulsion effects (tending to result in more extended structures) and stabilizing charge solvation effects in which the glycan plays a major role (tending to result in more compact structures). Taken together, these IMS and MD findings suggest the possibility of predicting and delineating glycopeptide-enriched regions of mass vs. mobility space for applications in glycoproteomics.