Genomics-Microbiome Based Assessment of Bidirectional Causality Between Gut Microbiota and Psoriasis.

Background: Traditional observational studies have found a possible risk association of the gut microbiota for psoriasis. Meanwhile, psoriasis may also affect the changes in the gut microbiota. However, the available evidence does not demonstrate a reciprocal relationship between the gut microbiota and psoriasis. This limits our understanding on the role of the gut microbiota in the mechanisms of psoriasis. Methods: To address this question we used Mendelian randomization, a novel epidemiological approach, and acquired the largest current gut microbiota GWAS data from the MiBioGen consortium as well as psoriasis GWAS data from the FinnGen consortium, and performed two-sample bidirectional MR analyses using a multiple MR analysis approach. Finally, the robustness of the results was assessed by sensitivity analysis. Results: Our results indicate that five bacterial genera are causally related to psoriasis and psoriasis is causally related to four bacterial genera. Conclusion: These results suggest a bidirectional causal influence of psoriasis on the gut microbiota. Our results somewhat challenge the causal inferences of previous observational studies. We found that the specific bacterial genera with a risk effect on psoriasis were different from those found to characterize psoriasis in previous observational studies, and that these psoriasis-characterizing genera were inversely associated with psoriasis.

Efficacy and safety of laser-related therapy for melasma: A systematic review and network meta-analysis.

BACKGROUND: Melasma is a prevalent, persistent hyperpigmentation disorder that negatively affects the psychological health of patients. However, the treatment outcome remains unsatisfactory due to the complexity of pathogenesis, recurrence characteristics, and relatively high morbidity. OBJECTIVES: To compare the performance of laser-related therapies in improving the melasma area severity index (MASI) score of melasma and the occurrence of adverse effects by network meta-analysis (NMA). METHODS: From the inception to November 2022, eligible randomized controlled trials were identified. Two investigators independently searched relevant studies from PUBMED, EMBASE, and the Cochrane Library database. RESULTS: A total of 39 clinical studies with 1394 participants were eligible for enrollment. For efficacy, the NMA demonstrated that Q-switched Nd: YAG laser + topical medications (QSND+TM) was superior to Q-switched Nd:YAG laser (QSND) [MD = -4.21 (-6.80, -1.63)], Er: YAG laser + topical medications (ERYL+TM) [MD = -3.52 (-6.84, -0.19)], and picosecond laser + topical medications (PICO+TM) [MD = -4.80 (-9.33, -0.27)]. The microneedling + topical medications (MN+TM) was superior to picosecond laser (PICO) [MD = -5.26 (-10.44, -0.08)] and topical medications (TM) [MD = -5.22 (-9.20, -1.23)]. The top five of the surface under the cumulative ranking curve value (SUCRA) are Q-switched Nd:YAG laser + topical medications (QSND+TM 85.9%), oral tranexamic acid (oTA 80.1%), microneedling + topical medications (MN+TM 79.7%), Q-switched Nd:YAG laser + intense pulse light (QSND+IPL 78.9%), and fractional carbon dioxide laser + topical medications (FCDL+TM 70.5%). CONCLUSIONS: In conclusion, the Qs-Nd:YAG laser with topical medications is the first choice for treating melasma according to the SUCRA value. Among the three treatment modalities, namely MN + TM, PICO, and TM, our recommendation favors MN+TM as the superior choice for enhancing the curative efficacy in melasma. However, the actual clinical choice should also take into account the adverse effects, the skin type of the patient, the duration of the disease, and other relevant factors.

Artificial intelligence-assisted dermatology diagnosis: From unimodal to multimodal.

Artificial Intelligence (AI) is progressively permeating medicine, notably in the realm of assisted diagnosis. However, the traditional unimodal AI models, reliant on large volumes of accurately labeled data and single data type usage, prove insufficient to assist dermatological diagnosis. Augmenting these models with text data from patient narratives, laboratory reports, and image data from skin lesions, dermoscopy, and pathologies could significantly enhance their diagnostic capacity. Large-scale pre-training multimodal models offer a promising solution, exploiting the burgeoning reservoir of clinical data and amalgamating various data types. This paper delves into unimodal models' methodologies, applications, and shortcomings while exploring how multimodal models can enhance accuracy and reliability. Furthermore, integrating cutting-edge technologies like federated learning and multi-party privacy computing with AI can substantially mitigate patient privacy concerns in dermatological datasets and further fosters a move towards high-precision self-diagnosis. Diagnostic systems underpinned by large-scale pre-training multimodal models can facilitate dermatology physicians in formulating effective diagnostic and treatment strategies and herald a transformative era in healthcare.

Successful Treatment of Psoriasis Combined with Bullous Pemphigoid with Dupilumab: A Case Report.

Psoriasis is an immune-mediated chronic inflammatory disease that can be combined with complications such as diabetes, cardiovascular disease, obesity, and kidney disease. The comorbidity of psoriasis with autoimmune bullous diseases (AIBD) has been reported previously in several cases, the most frequent of which is bullous pemphigoid (BP). The underlying mechanisms of psoriasis with BP are not clear and there are no uniform treatment criteria. Based on previous case reports, the coexistence of psoriasis and BP may be related to inflammatory activity, medications, phototherapy, and infection. We report a case of a psoriasis patient who developed BP after taking Chinese herbal compounds and was successfully treated with dupilumab, which is the first reported case of applying dupilumab to treat psoriasis with BP comorbidities.

Isolation and identification of hemostatic steroidal glycosides from Ypsilandra thibetica.

The phytoconstituents of the fraction with hemostatic activity of the 70% aqueous ethanol extract of Ypsilandra thibetica Franch. were investigated. As a result, fourteen previously unreported spirostanol saponins, ypsilandrosides Z1-Z14, and nine known analogues were isolated and characterized by MS, NMR, and chemical methods. Among them, ypsilandrosides Z1-Z4 (1-4) have a rare 12-O-ß-d-glucopyranosyl group, while ypsilandrosides Z5-Z8 (5-8) possess a rare double bond between C-4 and C-5, and a hydroxyl or carbonyl located at the C-6. All isolates were further tested for their hemostatic activity. The results suggested that five spirostanol tetraglycosides show favorable inducing platelet aggregation activities. Among them, ypsilandroside G (16) displayed significant inducing platelet aggregation activity with an EC50 value of 57.17 µM. Furthermore, the preliminary structure-activity relationship of these spirostanol glycosides' hemostatic activity was discussed.

Ypsilandrosides U-Y, five new steroidal saponins from Ypsilandra thibetica.

Phytochemical reinvestigation on the whole plants of Ypsilandra thibetica obtained four new spirostanol glycosides, named ypsilandrosides U-X (1-4), and one new cholestanol glycoside, named ypsilandroside Y (5). Their structures have been established by extensive spectroscopic data and chemical methods. Among them, compound 4 is a rare spirostanol glycoside which possesses a novel 5(6 → 7) abeo-steroidal aglycone, while compound 1 is a first spirostanol bisdesmoside attached to C-3 and C-12, respectively, isolated from the genus Ypsilandra. The induced platelet aggregation activity of the isolates was tested.

Giant urethral calculus in anterior urethral diverticulum: a case report.

BACKGROUND: In this case report, giant calculus in the urethral diverticulum was found through ureteroscopy investigation, the pneumatic lithotripsy combined with ultrasound lithotripsy (PLCUL) was successfully performed to break down this rare and giant urethral calculus in the diverticulum without open surgery. CASE PRESENTATION: A 82-year-old male presented to the urology department, complaining of frequent urination and dysuria. One giant, dark brown stone (6.5 × 6 × 5.5 cm) was revealed in the diverticulum of the anterior urethra using combination of local ultrasound, pelvic Computer Tomography (CT) and Magnetic Resonance Imaging (MRI). The stone was then successfully broken down via the PLCUL, and the emptied anterior urethral diverticulum was left untreated. In the 18 months' follow-up, no new calculus was found in urethral tract, anterior diverticula became gradually smaller, eventually disappeared. CONCLUSION: In the treatment of giant calculus in the urethral diverticulum, this case report provides an effective method of lithotripsy in the clinical trials.

MicroRNA-125a suppresses cell migration, invasion, and regulates hyaluronic acid synthase 1 expression by targeting signal transducers and activators of transcription 3 in renal cell carcinoma cells.

Renal cell carcinoma (RCC) is one of the most common cancers in urology. MicroRNA-125a (miR-125a) has been demonstrated to be implicated in various cancers. However, the functional role of miR-125a in RCC remains largely unclear. This study was aimed to investigate the functional role of miR-125a and the expression relevance of signal transducers and activators of transcription 3 (STAT3) with hyaluronic acid synthase 1 (HAS1) in RCC. We revealed that miR-125a was downexpressed in 786-O cells, and examined transfected efficiency. According to functional assay, overexpression of miR-125a inhibited cell migration and cell invasion, but no obvious effect was observed on cell proliferation. The luciferase activity assay showed that miR-125a could directly target STAT3 3'-untranslated regions. Meanwhile, quantitative polymerase chain reaction (qPCR) assay and Western blot analysis demonstrated that miR-125a could inhibit STAT3 expression at both messenger RNA and protein levels. Furthermore, the combination sites between STAT3 and HAS1 were predicted by prediction of transcription factor binding sites database analysis. The expression of STAT3 was correlated with HAS1 expression, exemplified by the same tendency detected by qPCR assay. Taken together, our results preliminarily demonstrate that miR-125a could constrain cell migration, invasion, and regulate HAS1 expression in RCC cells by targeting STAT3. It is likely to facilitate a better understanding of the regulation mechanisms of miR-125a in RCC.

AnnexinA7 down-regulation might suppress the proliferation and metastasis of human hepatocellular carcinoma cells via MAPK/ ERK pathway.

BACKGROUND: Hepatocellular carcinoma is one of the most fatal malignancies worldwide with high lethality. However, the exact mechanism of liver tumorigenesis is still unclear. AnnexinA7 (ANXA7) is a Ca2+-binding protein which is involved in membrane organization and dynamics and indicated a role of ANXA7 in cancer. However, the action of ANXA7 in hepatocellular carcinoma and the relative mechanism is still indistinct. OBJECTIVE: To gain more insight into the biological function of ANXA7 and assess its possible influence on proliferation and metastasis capacity of human hepatocellular carcinoma cells with the relative mechanism. METHODS: ANXA7 was down-regulated by RNA interference in both HepG2 and smmc-7721 cells. The decreased cell proliferation was detected by MTT method and colony formation assay. To confirm the result of cell proliferation, Ki-67 and cyclinD1 expression was examined by Western Blot. The increased apoptosis capacity of the cells was detected with cell cytometry and PI staining respectively. Bcl-2 and Bax expression was further investigated by Western blot and the decreased ration of Bcl-2/Bax might explain the increased apoptosis. RESULTS: Cell metastasis showed significantly limited ability which was tested by wound healing assay and Transwell assay. Meanwhile, the key biomarkers of cell metastasis E-cadherin expression increased while MMP-9 decreased. Furthermore, we found that ANXA7 played its role via MAPK/ERK pathway. CONCLUSIONS: ANXA7 might involve in the development of hepatocellular carcinoma and act as an oncogene which might be a potential therapeutic target for treatment.

Annexin A5 overexpression might suppress proliferation and metastasis of human uterine cervical carcinoma cells.

BACKGROUND: Annexin A5 (ANXA5) is a kind of Ca2+-dependent phospholipid binding protein which is involved in cell membrane dynamics and organization. Recent data showed that ANXA5 might involve in tumorigenesis. OBJECTIVE: To explore what role ANXA5 play in human uterine cervical carcinoma. MATERIALS AND METHODS: In this study, a recombined ANXA5 plasmid was constructed and uterine cervical carcinoma cell lines HeLa and SiHa were transfected with it. After ANXA5 overexpression was determined by Western Blot, cell proliferation test was detected by MTT assay and colony formation assay respectively. FACS assay and Hochest33258 staining methods were employed to detect cell apoptosis. To further investigate whether ANXA5 influence cell migration and invasion, wound healing assay and transwell assay were applied. At the same time, the relative mechanism was investigated. RESULTS: When ANXA5 expression increased, cell proliferation was inhibited by regulating the expression of bcl-2 and bax while cell metastasis was suppressed by regulating E-cadherin and MMP-9 expression. CONCLUSION: ANXA5 overexpression in the uterine cervical carcinoma might play important roles in cell proliferation and metastasis of uterine cervical cancer cells and act as an anti-cancer gene in uterine cervical cancer.