[The causal relationship between gut microbiota and male reproductive and sexual health].

OBJECTIVE: The purpose of this study was to use the MR method to explore the causal relationship between 211 gut microbiota and male reproductive and sexual health. METHODS: The MiBioGen alliance published genome-wide association study (GWAS) related genetic variation data was used as instrumental variables (IVs) for gut microbiota, and the Finngen biobank GWAS related genetic variation data was used as IVs for male infertility, abnormal sperm, sexual dysfunction, erectile dysfunction, and testicular dysfunction. The inverse variance-weighted (IVW) method was used as the MR analysis method, the results were evaluated according to the odds ratio and 95% confidence interval of the effect measures, and data sensitivity analysis was performed. RESULTS: The results showed that 6 types of gut microbiota were related to male infertility, 12 types were related to abnormal sperm, 5 types were related to sexual dysfunction, 4 types were related to erectile dysfunction, and 4 types were related to testicular dysfunction. And there was no abnormality in the data sensitivity analysis. CONCLUSION: The intestinal microbiota is closely related to male reproductive and sexual health.

Successful combination therapy for severe infantile hemangiomas: case report and literature search.

Infantile hemangiomas are common benign vascular tumors of infancy. Although the majority of uncomplicated hemangiomas involute spontaneously, rapid-growth lesions with complications need early active intervention. On the other hand, severe and complicated lesions can be difficult to treat. Recently, we successfully treated two cases of giant severe infantile facial hemangiomas using local application of bleomycin and pulsed dye laser along with systemic application of dexamethasone. Our results suggest that the multiple modalities of bleomycin, laser, and corticosteroid are a safe and effective approach for early therapeutic intervention of severe facial hemangiomas.

Photodynamic therapy in treatment of port wine stain birthmarks--recent progress.

Port wine stain (PWS) birthmarks are congenital vascular malformations characterized by ectatic capillaries in the papillary layer of the dermis. They usually appear at birth and tend to become darker and thicker with age. Cosmetic and pathological changes can cause great depression in all ages. Laser-mediated selective photothermolysis is the treatment of choice but vascular-targeted photodynamic therapy (PDT) might be an alternative approach in the treatment of PWS. PDT has shown therapeutic benefit in pink and resistant lesions. In theory, vascular-targeted PDT may be more efficient in terms of better lightening and less treatment sessions than pulsed dye laser (PDL) irradiation. Chinese clinicians have gained profound knowledge and accumulated a large body of clinical experience in PWS PDT in the past years. The pursuing of regulatory approval on PWS PDT is currently underway. In this article we will report our experience in PWS PDT, discuss current PDT protocols and introduce the novel combination therapy, such as PDT+PDL and PDT+topical angiogenic inhibitor.

[Effect of alexandrite laser treatment for hair removal in Tibet mini-pigs].

OBJECTIVE: To observe the histological and ultrastructural changes of the skin and hair follicles following hair removal by alexandrite laser in Tibet mini-pigs. METHODS: Twelve healthy Tibet mini-pigs with dark hair were treated with alexandrite laser for hair removal. The skin specimens were taken immediately and at 1 h and 1, 3, 5, 10, 15, 30, 60 days after the laser treatment for observation under optical and transmission electron microscope. RESULTS: Laser hair removal resulted in extensive coagulation necrosis, carbonization and falling of the subcutaneous hair shafts, and some of the cells in the outer root sheath and hair bulb underwent degenerative and necrotic changes. One hour after laser treatment, the cells in the outer root sheath and bulb exhibited nuclear condensation, fragmentation and or karyolysis characteristic of cell apoptosis. The cell apoptosis reached the peak level on day 3 after the laser exposure, accompanied by endothelial degeneration in the hair papilla vessels, edema and lymphocyte infiltration in the dermal tissues. Tissue reaction and inflammation were relieved on day 5, and the dermal tissue and follicles recovered their normal structures on day 10. At 60 days after the treatment, the hair follicles decreased markedly but the structure of the residue follicles remained normal. CONCLUSION: Alexandrite laser exposure results in selective destruction of the follicles by inducing direct coagulation and cell apoptosis to achieve permanent hair removal. Tibet mini-pigs with black hair can be used as the animal model of clinical laser hair removal.

Comparison of photodynamic therapy and pulsed dye laser in patients with port wine stain birthmarks: a retrospective analysis.

BACKGROUND: Photodynamic therapy (PDT) might be an alternative approach for treating port wine stains (PWS). This study attempts to compare clinical outcomes of PDT versus conventional pulsed dye laser (PDL) in Chinese patients. METHODS: Retrospective analysis of medical records of a single hospital. PDL was delivered by a 585 nm laser. PDT was carried out by a combination of hematoporphyrin monomethyl ether (HMME) and copper vapour laser (510.6 and 578.2 nm). Clinical outcomes were graded based on photographs. RESULTS: The children group (3-10 years old) included 210 patients (PDL=112 and PDT=98) with pink flat PWS located in the cheek region. The overall fair to excellent response was 95.5% in PDL group and 88.8% PDT group (P=0.901), respectively. The excellent response rate of PDT group (23.5%) was higher than that of PDL group (16.1%). The adult group (18-30 years old) included 371 patients (PDL=163 and PDT=208) with purple flat PWS located in the temple, cheek or neck region. The overall fair to excellent response in PDL and PDT group was 88.4 and 94.2% (P<0.001), respectively. The excellent response rate of PDT group (37.5%) was significantly higher than that of PDL group (3.1%). The complication rate (pigmentary or textural change) in PDT group (10.2%) was lower than that in PDL group (24.7%). CONCLUSIONS: PDT is as effective as PDL for pink flat lesions and is more effective than PDL for purple flat lesions. The true value of PDT deserves further investigation.

[Role of angiotensin II receptors in proliferation of fibroblast derived from human hypertrophic scars].

OBJECTIVE: The present study was undertaken to observe the expression of angiotensin II (Ang II) type 1 (AT1) and type 2 (AT2) receptors in human hypertrophic scars, and explore their role in the proliferation of fibroblasts in human hypertrophic scars. METHODS: The expression of both ATL and AT2 receptors in fibroblasts of hypertrophic scars was detected with immunohistochemical staining. Radioligand receptor binding assay and RT-PCR were used to determined expression level of AT1 and AT2 receptors in cultured fibroblasts derived from hypertrophic scars. DNA synthesis was examined in cultured fibroblasts of hypertrophic scars by measuring [3H]-TdR incorporation into fibroblasts. RESULTS: Positive staining signals of both AT1 and AT2 receptors were found in fibroblasts of hypertrophic scars. Expression level of AT1 and AT2 receptors were (10.69 +/- 2.15) fmol/10(6) cells, (4.9 +/- 1.05) fmol/10(6) cells respectively in cultured fibroblasts derived from hypertrophic scars. RT-PCR showed the similar results. In cultured fibroblasts, Ang II stimulation significantly increased DNA synthesis (P < 0.05 vs negative control), which was inhibited by valsartan, an AT1 receptor blocker, but augmented by PD123319, an AT2 receptor antagonist. Valsartan or PD123319 alone did not influence the proliferation of fibroblasts derived from hypertrophic scars. CONCLUSIONS: Both AT1 and AT2 receptors were expressed in the fibroblasts of hypertrophic scars, and Ang II regulates DNA synthesis in hypertrophic scar fibroblasts through a negative cross-talk between AT1 and AT2 receptors, which might contribute, at least partly to formation and maturation of human hypertrophic scars. The present study provides new insight into pathogenesis of hypertrophic scars.

Angiotensin II regulates phosphoinositide 3 kinase/Akt cascade via a negative crosstalk between AT1 and AT2 receptors in skin fibroblasts of human hypertrophic scars.

Angiotensin II (Ang II) stimulation has been shown to regulate proliferation of skin fibroblasts and production of extracellular matrix, which are very important process in skin wound healing and scarring; however, the signaling pathways involved in this process, especially in humans, are less explored. In the present study, we used skin fibroblasts of human hypertrophic scar, which expressed both AT1 and AT2 receptors, and observed that Ang II increased Akt phosphorylation and phosphoinositide 3 kinase (PI 3-K) activity. In addition, the Ang II-induced Akt phosphorylation was blocked by wortmannin, a PI 3-K inhibitor. This Ang II-activated PI 3-K/Akt cascade was markedly inhibited by valsartan, an AT(1) receptor-specific blocker, whereas it was enhanced by PD123319, an AT(2) receptor antagonist. On the other hand, the Ang II- or EGF-induced activation of PI 3-K/Akt was strongly attenuated by AG1478, an inhibitor of epidermal growth factor (EGF) receptor kinase. Moreover, Ang II stimulated tyrosine phosphorylation of EGF receptor and p85alpha subunit of PI 3-K accompanied by an increase in their association, which was inhibited by valsartan, and enhanced by PD123319. The Ang II-induced transactivation of EGF receptor resulted in activation of extracellular signal-regulated kinase (ERK) that was also inhibited by valsartan, and enhanced by PD123319. Taken together, our results showed that AT(1) receptor-mediated activation of PI 3-K/Akt cascades occurs at least partially via the transactivation of EGF receptor, which is under a negative control by AT(2) receptor in hypertrophic scar fibroblasts. These findings contribute to understanding the molecular mechanism of human hypertrophic scar formation.

Mix-infections with different genotypes of HCV and with HCV plus other hepatitis viruses in patients with hepatitis C in China.

AIM: Clinical therapy and prognosis in HCV infections are not good, and mix-infections with different HCV genotypes or quasispecies and mix-infections with HCV plus other hepatitis viruses are important concerns worldwide. The present report describes the sequence diversity and genotying of the 5'NCR of HCV isolates from hepatitis patients mix-infected with different HCV genotypes or variants, and the conditions of mix-infections with HCV plus other hepatitis viruses, providing important diagnostic and prognostic information for more effective treatment of HCV infections. METHODS: The 5' non-coding region (5'NCR) of HCV was isolated from the patients sera and sequenced, and sequence variability and genotypes of HCV were defined by nucleotide sequence alignment and phylogenetic analysis, and the patients mix-infected with HCV plus other hepatitis viruses were analyzed. The conditions and clinical significance of mix-infections with HCV plus other hepatitis viruses were further studied. RESULTS: Twenty-four out of 43 patients with chronic hepatitis C were defined as mix-infected with different genotypes of HCV. Among these 24 patients, 9 were mix-infected with genotype 1 and 3, 7 with different variants of genotype 1, 2 with different variants of genotype 2, 6 with different variants of genotype 3. No patients were found mix-infected with genotype 1 and 2 or with genotype 2 and 3. The clinical virological analysis of 60 patients mix-infected with HCV plus other hepatitis viruses showed that 45.0 % of the patients were mix-infected with HCV plus HAV, 61.7 % with HCV plus HBV, 6.7 % with HCV plus HDV/HBV, 8.4 % with HCV plus HEV, 3.3 % with HCV plus HGV. Infections with HCV plus other hepatitis viruses may exacerbate the pathological lesion of the liver. CONCLUSION: The findings in the present study imply that mix-infections with different HCV genotypes and mix-infections with HCV plus other hepatitis viruses were relatively high in Yunnan, China, providing important diagnostic and prognostic information for more effective treatment of HCV infections.

Sequence variability of the 5' UTR in isolates of hepatitis C virus in China.

BACKGROUND: Hepatitis C virus infection is a great issue in China; however, there is very little information on genotyping investigations based on sequence variability in the 5'untranslated (5'UTR) reported. The present study was to define the sequence variability based on the sequence divergences of the 5'UTR of the virus. METHODS: Sequences of 91 isolates from patients with chronic hepatitis C from Yunnan, southwest China, were sequenced and genotypes were defined according to the sequence divergences of the 5'UTR of the virus. RESULTS: Eighty-six isolates were classified into 3 clades (previously termed groups or major types) by the methods proposed by Chan et al in 1992 and phylogenetic analysis based on nucleotide sequence divergences within the 5'UTR. Fifty-six percent of the isolates were classified into clade 3, 35% into clade 1, and 34.9% into clade 2. New genotypes 1f, 2h, 3h and 3i were defined. In addition, 3 novel sequences were discovered, respectively with an 18-nt sequence deletion (corresponding to nucleotide position -173 to -156), a 28-nt sequence insertion, and a 40-nt sequence insertion, between -56 and -55. Of these isolates, 56% possessed a "G" at position -66 in place of the "T" that is present in all previously reported sequences. CONCLUSIONS: These HCV variants, evolved or remained in this area, may be of great significance in diagnosis and treatment of hepatitis C patients.

Hepatitis C virus infections and genotypes in China.

OBJECTIVE: To define the conditions of hepatitis C virus (HCV) infections, and geographic and demographic distributions of genotypes in China. METHODS: HCV infected patients were selected from individuals with different patterns of liver diseases and high risk populations in different parts of China. Genotypes of HCV in some isolates were further analyzed, based on the data from our laboratory studies and some carefully selected published literatures. RESULTS: The anti-HCV positive rates were 9.7% in patients with acute hepatitis, 13.3% in patients with chronic hepatitis, 18.3% in patients with hepatocellular carcinoma, 33.0% in patients with liver cirrhosis, and 43.2% in patients with posttransfusional hepatitis (average, 16.2% in patients with liver diseases). The anti-HCV positive rates in the high risk populations were 36.4% in leukemic patients, 43.0% in hemodialysis patients, 12.7% in blood donors, 64.1% in drug abusers, 13.1% in prostitutes, and 2.57% in naturally healthy people. At least 4 clades (clades 1, 2, 3 and 6) of HCV were found in China with different geographic and demographic distributions. Genotype 1b was the most widely distributed genotype, and genotype 3 was mainly found in Yunnan Province, Southwest China. CONCLUSION: China has a high incidence of HCV infection. Our results will provide a strategic basis for diagnosis, treatment and possibly prophylaxis of hepatitis C virus diseases.