The effect of dipeptidyl peptidase-4 inhibitor on incidence and clinical course in bullous pemphigoid patients in a tertiary medical center.

Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second-line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i-associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case-control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12-month follow-up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off-therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p = 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p = 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off-therapy were also noted in the DPP4i-continuance group within 12 months of follow-up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.

Smart humancentric lighting system improves sleep efficiency of nursing home residents.

The global phenomenon of population aging presents a significant challenge, affecting both the increasing number of older individuals and their duration of living with disability. Tailored care services are crucial for improving the quality of life of older adults, particularly those with disabilities residing in nursing homes. However, ensuring personalized care and mitigating the risks associated with institutionalization are essential in optimizing care quality. One particular challenge in nursing homes is maintaining residents' personal routines and addressing sleep disturbances linked to neurodegenerative disorders. Non-pharmacological interventions are increasingly recognized as preventive and management strategies for behavioral and psychiatric symptoms in nursing home residents. Sleep disruptions, such as reduced duration and increased nocturnal awakenings, are prevalent among nursing home residents. Excessive nocturnal lighting and frequent caregiver interventions contribute to these disturbances. This study aimed to investigate the impact of implementing smart humancentric lighting on the sleep efficiency of nursing home residents. Data from pressure sensors embedded in mattresses were collected to assess sleep efficiency. The findings suggest that smart humancentric lighting can significantly reduce sleep disturbances and improve sleep quality in nursing home residents. Future research should delve into specific symptoms, care burden, and psychotropic agent utilization to validate the effectiveness of this intervention.

Promoting Photosynthetic Production of Dammarenediol-II in Chlamydomonas reinhardtii via Gene Loading and Culture Optimization.

Ginsenosides are major bioactive compounds found in Panax ginseng that exhibit various pharmaceutical properties. Dammarenediol-II, the nucleus of dammarane-type ginsenosides, is a promising candidate for pharmacologically active triterpenes. Dammarenediol-II synthase (DDS) cyclizes 2,3-oxidosqualene to produce dammarenediol-II. Based on the native terpenoids synthetic pathway, a dammarane-type ginsenosides synthetic pathway was established in Chlamydomonas reinhardtii by introducing P. ginseng PgDDS, CYP450 enzyme (PgCYP716A47), or/and Arabidopsis thaliana NADPH-cytochrome P450 reductase gene (AtCPR), which is responsible for producing dammarane-type ginsenosides. To enhance productivity, strategies such as "gene loading" and "culture optimizing" were employed. Multiple copies of transgene expression cassettes were introduced into the genome to increase the expression of the key rate-limiting enzyme gene, PgDDS, significantly improving the titer of dammarenediol-II to approximately 0.2 mg/L. Following the culture optimization in an opt2 medium supplemented with 1.5 mM methyl jasmonate under a light:dark regimen, the titer of dammarenediol-II increased more than 13-fold to approximately 2.6 mg/L. The C. reinhardtii strains engineered in this study constitute a good platform for the further production of ginsenosides in microalgae.

Response predictor for pigment reduction after one session of photo-based therapy using convolutional neural network: A proof of concept study.

BACKGROUND: Identifying treatment responders after a single session of photo-based procedure for hyperpigmentary disorders may be difficult. OBJECTIVES: We aim to train a convolutional neural network (CNN) to test the hypothesis that there exist discernible features in pretreatment photographs for identifying favorable responses after photo-based treatments for facial hyperpigmentation and develop a clinically applicable algorithm to predict treatment outcome. METHODS: Two hundred and sixty-four sets of pretreatment photographs of subjects receiving photo-based treatment for esthetic enhancement were obtained using the VISIA® skin analysis system. Preprocessing was done by masking the facial features of the photographs. Each set of photographs consists of five types of images. Five independently trained CNNs based on the Resnet50 backbone were developed based on these images and the results of these CNNs were combined to obtain the final result. RESULTS: The developed CNN algorithm has a prediction accuracy approaching 78.5% with area under the receiver operating characteristic curve being 0.839. CONCLUSION: The treatment efficacy of photo-based therapies on facial skin pigmentation can be predicted based on pretreatment images.

Comparing high-dose dual therapy with bismuth-containing quadruple therapy for the initial eradication of Helicobacter pylori infection on Hainan Island: A randomized, multicenter clinical trial.

BACKGROUND: Traditional bismuth-containing quadruple therapy, as a first-line eradication treatment for Helicobacter pylori (H. pylori), has several disadvantages, including drug side effects, low medication adherence, and high costs. Trials of high-dose dual treatment have demonstrated its advantages, which include good safety and adherence profiles. In this study, we investigated the efficacy, safety, and compliance of a high-dose dual therapy when compared with bismuth-based quadruple treatment for the initial eradication of H. pylori infection on Hainan Island, China. METHODS: We randomized 846 H. pylori-infected patients into two groups. A bismuth-containing quadruple therapy group was administered the following: esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily, and colloidal bismuth pectin in suspension 150 mg three times/day for 2 weeks. A high-dose dual therapy group was administered the following: esomeprazole 20 mg four times/day and amoxicillin 1000 mg three times/day for 2 weeks. Patients were given a 13C urea breath test at 4 weeks at treatment end. Adverse effects and compliance were evaluated at follow-up visits. RESULTS: Eradication rates in the high-dose dual therapy group were: 90.3% (381/422, 95% confidence interval [CI]: 87.1%-92.9%) in intention-to-treat (ITT) and 93.6% (381/407, 95% CI: 90.8%-95.8%) in per-protocol (PP) analyses. Eradication rates were 87.3% in ITT (370/424, 95% CI: 83.7%-90.3%) and 91.8% in PP analyses (370/403, 95% CI: 88.7%-94.3%) for quadruple therapy, with no statistical differences (P = 0.164 in ITT and P = 0.324 in PP analyses). Adverse effects were 13.5% (55/407) in the dual group and 17.4% (70/403) in the quadruple group (P = 0.129). Compliance was 92.4% (376/407) in the dual group and 86.6% (349/403) in the quadruple group (P = 0.007). CONCLUSIONS: High-dose dual therapy had high eradication rates comparable with bismuth-based quadruple treatment, with no differences in adverse effects, however higher adherence rates were recorded.

The impact of the COVID-19 surge on phototherapy in Taiwan: Focusing on the patient profile, adherence, and attitude before and after the surge.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused changes in the medical practice. However, it is unclear whether the patients receiving phototherapy for their dermatoses have been affected. OBJECTIVES: This study aimed to identify the impact of the COVID-19 pandemic on phototherapy, focusing on the patient profile, adherence, and attitude before and after the surge. METHODS: The study encompassed the time 5 months prior to and after the surge of the COVID-19 pandemic (from May to July, 2021), resulting in the temporary closure of our phototherapeutic unit. RESULTS: Nine hundred eighty-one patients received phototherapy during this period. Vitiligo, psoriasis (Ps), and atopic dermatitis (AD) represented the groups with the highest patient numbers. For vitiligo, Ps and AD, 39.6%, 41.9%, and 28.4% of the patients resumed phototherapy after the pandemic-related shutdown (PRS). No significant difference was noted in age, gender, and number of weekly sessions between those who resumed or stopped phototherapy after PRS among three groups. Patients who resumed phototherapy after PRS tended to receive more weekly sessions of phototherapy than those who initiated after PRS. Additionally, patients who resumed phototherapy showed no significant difference in the number of weekly sessions before and after PRS. CONCLUSIONS: This study reveals a significant impact of the COVID-19 pandemic on patients undergoing phototherapy. Although the patient number remained similar before and after PRS, a significant portion of patients discontinued phototherapy after PRS. New strategies and continued education are needed to improve patient management in times of pandemic.

Adenosine 2A receptor contributes to the facilitation of post-infectious irritable bowel syndrome by γδ T cells via the PKA/CREB/NF-κB signaling pathway.

BACKGROUND: Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome (PI-IBS). γδ T cells play a crucial role in innate and adaptive immunity. Adenosine receptors expressed on the surface of γδ T cells participate in intestinal inflammation and immunity regulation. AIM: To investigate the role of γδ T cell regulated by adenosine 2A receptor (A2AR) in PI-IBS. METHODS: The PI-IBS mouse model has been established with Trichinella spiralis (T. spiralis) infection. The intestinal A2AR and A2AR in γδ T cells were detected by immunohistochemistry, and the inflammatory cytokines were measured by western blot. The role of A2AR on the isolated γδ T cells, including proliferation, apoptosis, and cytokine production, were evaluated in vitro. Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction (RT-PCR). The animals were administered with A2AR agonist, or A2AR antagonist. Besides, γδ T cells were also injected back into the animals, and the parameters described above were examined, as well as the clinical features. Furthermore, the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR. RESULTS: PI-IBS mice exhibited elevated ATP content and A2AR expression (P < 0.05), and suppression of A2AR enhanced PI-IBS clinical characteristics, indicated by the abdominal withdrawal reflex and colon transportation test. PI-IBS was associated with an increase in intestinal T cells, and cytokine levels of interleukin-1 (IL-1), IL-6, IL-17A, and interferon-α (IFN-α). Also, γδ T cells expressed A2AR in vitro and generated IL-1, IL-6, IL-17A, and IFN-α, which can be controlled by A2AR agonist and antagonist. Mechanistic studies demonstrated that the A2AR antagonist improved the function of γδ T cells through the PKA/CREB/NF-κB signaling pathway. CONCLUSION: Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function of γδ T cells via the PKA/CREB/NF-κB signaling pathway.

The Epidermal Keratinocyte as a Therapeutic Target for Management of Diabetic Wounds.

Diabetes mellitus (DM) is an important cause of chronic wounds and non-traumatic amputation. The prevalence and number of cases of diabetic mellitus are increasing worldwide. Keratinocytes, the outermost layer of the epidermis, play an important role in wound healing. A high glucose environment may disrupt the physiologic functions of keratinocytes, resulting in prolonged inflammation, impaired proliferation, and the migration of keratinocytes and impaired angiogenesis. This review provides an overview of keratinocyte dysfunctions in a high glucose environment. Effective and safe therapeutic approaches for promoting diabetic wound healing can be developed if molecular mechanisms responsible for keratinocyte dysfunction in high glucose environments are elucidated.

Investigation of the keratinocyte transcriptome altered in high-glucose environment: An in-vitro model system for precision medicine.

BACKGROUND: Impaired wound healing is a serious diabetes complication compromising patients' quality of life. However, the pathogenesis of diabetic wounds (DWs) remains incompletely understood. Human epidermal keratinocyte (HEK) is the sentinel cell that initiates healing processes after the epidermal integrity has been disrupted. OBJECTIVE: This study aimed to investigate the functional roles of HEKs in wound healing and to identify candidate genes, signaling pathways and molecular signatures contributing to the DWs. METHODS: HEKs were cultured in normal or high-glucose environment, followed by scratch, to mimic the microenvironment of normal wounds and DWs. Subsequently, we performed RNA sequencing and systematically analyzed the expression profiles by bioinformatics approaches. RESULTS: High-glucose environment altered the keratinocyte transcriptome responses to wounding. In experimental model of DWs, we found that TNF, CYP24A1, NR4A3 and GGT1 were key overexpressed genes in keratinocytes and were implicated in multiple cellular responses. Further analysis showed that wounding in high-glucose environment activated G-protein-coupled receptor (GPCR) signaling, cAMP response element-binding protein (CREB) signaling, and adrenomedullin signaling in keratinocytes, while dysregulated skin development and immune responses as compared to their counterpart in normal glucose settings. CONCLUSION: This simplified in-vitro model serves as a valuable tool to gain insights into the molecular basis of DWs and to facilitate establishment of personalized therapies in clinical practice.

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

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

Interaction of B-group streptococcal infection and chorioamnionitis in low birth weight infants during late pregnancy / 中国医师杂志

Objective:To investigate the interaction of B-group streptococcal infection and chorioamnionitis (CAM) with late pregnancy and low birth weight infant (LBWI).Methods:A retrospective study was conducted on 524 postpartum women who underwent regular prenatal examinations and completed delivery at the Taizhou Second People′s Hospital from October 2019 to April 2022. According to their newborn birth weight, they were divided into normal group (466 cases) and LBWI group (58 cases). The age, pregnancy times, birth times, pregnancy body mass index (BMI), cesarean section history, abortion history, anemia during pregnancy, hypertensive disorder during pregnancy, diabetes during pregnancy, vaginitis, B-group streptococcal infection, CAM, premature rupture of membranes, postpartum hemorrhage, puerperal infection, neonatal preterm delivery, neonatal asphyxia, neonatal infection, fetal distress were compared between the two groups. The influencing factors of LBWI were analyzed using logistic regression. The correlation and interaction between B-group streptococcal infection and CAM on LBWI were analyzed.Results:There was a statistically significant difference in age, history of miscarriage, gestational hypertension, vaginitis, B-group streptococcal infection, CAM, premature rupture of membranes, neonatal preterm birth, neonatal infection and fetal distress between the two groups (all P<0.05). The results of logistic regression analysis showed that gestational hypertension, B-group streptococcal infection, CAM, premature rupture of membranes, preterm birth, neonatal infection, and fetal distress were risk factors for LBWI (all P<0.05). B-group streptococcal infection, CAM, and LBWI were positively correlated ( r=0.587, 0.604, all P<0.001). The interaction analysis results showed a positive correlation between B-group streptococcal infection, CAM, and LBWI (all P<0.001). Conclusions:B-group streptococcal infection in late pregnancy, CAM, and LBWI are positively correlated, and their coexistence can increase the risk of LBWI.

Expression and significance of ecto-5'-nucleotidase in colon tissue of Crohn's disease mice / 中国热带医学

@#Abstract: Objective This study aimed to investigate the expression of CD73 in colonic tissues in Crohn's disease (CD) and its significance and possible mechanism of action. Methods Thirty male BALB/c mice were randomly divided into normal control group, model group and intervention group. The control group was fed normally, and the model group was treated with TNBS+40% alcohol enema to establish a mouse model of Crohn's disease induced by chronic inflammation. The intervention group was treated with AB-680 intraperitoneally on the second day of each enema based on the model group. Mice body weight, fecal traits and fecal occult blood were recorded for disease activity index (DAI) score of inflammatory bowel disease. The animals were sacrificed at 7th week, their colonic tissues were removed, weighed and measured. The tissue inflammation was observed by standard hematoxylin-eosin (HE) staining. Masson staining was used to measure the area of collagen in colon tissue of mice. CD73 was detected by fluorescence quantitative PCR and immunohistochemistry. The expression levels of TGF-β, TNF-α and IL-6 in colon tissue of mice were determined by ELISA. Results The DAI score was (0.10±0.16) in the control group, (2.80±0.79) in the model group, and (3.07±0.34) in the intervention group. Compared with the control group, the DAI scores of the model and intervention groups were increased significantly (P<0.05). Compared with the model group, the DAI score of the intervention group was significantly increased (P<0.05). HE staining showed that there was no inflammation in the colon of the control group, while the colon of the model group and the intervention group showed typical inflammatory manifestations such as edema and congestion, inflammatory cell infiltration, and mucosal ulcer. The area ratio of collagen in the control group was (4.95±0.82)%, in the model group was (24.62±1.46)%, and in the intervention group was (54.47±2.75)%. Compared with the control group, the area ratio of collagen in the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the area ratio of collagen in the intervention group was significantly increased (P<0.05). Compared with the control group, the expression of CD73 in colon tissue of the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the expression of CD73 in colon tissue of the intervention group was decreased (P<0.05). Compared with the control group, the expressions of TGF-β, TNF-α and IL-6 in the model group and the intervention group were significantly increased (P<0.05). Compared with the model group, the expression of TGF-β, TNF-α and IL-6 in the intervention group decreased (P<0.05). Conclusions CD73 is upregulated in colon tissue of CD mice, it can inhibit inflammatory reaction and improve fibrosis by up-regulating TGF-β expression. On the other hand, CD73 can aggravate the inflammatory response in CD intestinal inflammation and fibrosis by up-regulating the expression of IL-6 and TNF-α. Therefore, CD73 may play a bidirectional regulatory role in intestinal inflammation and fibrosis of CD.

A membrane-based seawater electrolyser for hydrogen generation.

Electrochemical saline water electrolysis using renewable energy as input is a highly desirable and sustainable method for the mass production of green hydrogen1-7; however, its practical viability is seriously challenged by insufficient durability because of the electrode side reactions and corrosion issues arising from the complex components of seawater. Although catalyst engineering using polyanion coatings to suppress corrosion by chloride ions or creating highly selective electrocatalysts has been extensively exploited with modest success, it is still far from satisfactory for practical applications8-14. Indirect seawater splitting by using a pre-desalination process can avoid side-reaction and corrosion problems15-21, but it requires additional energy input, making it economically less attractive. In addition, the independent bulky desalination system makes seawater electrolysis systems less flexible in terms of size. Here we propose a direct seawater electrolysis method for hydrogen production that radically addresses the side-reaction and corrosion problems. A demonstration system was stably operated at a current density of 250 milliamperes per square centimetre for over 3,200 hours under practical application conditions without failure. This strategy realizes efficient, size-flexible and scalable direct seawater electrolysis in a way similar to freshwater splitting without a notable increase in operation cost, and has high potential for practical application. Importantly, this configuration and mechanism promises further applications in simultaneous water-based effluent treatment and resource recovery and hydrogen generation in one step.