The burden of skin diseases in China: global burden of Disease Study 2019.

Skin diseases continue to affect human health and cause a significant disease burden on the healthcare system.We aimed to report the changing trends in the burden of skin disease in China from 1990 to 2019, Which has an important role in developing targeted prevention strategies. We applied Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 analytical tools to calculate the age-standardized Prevalence and Incidence in 2019, number of years lived with disability (YLDs) and age-standardized YLDs from 1990 to 2019 of skin and subcutaneous diseases, notifiable infectious skin diseases and skin tumors in China. Among the skin and subcutaneous diseases in China in 2019, dermatitis contributed to the greatest YLD (2.17 million, 95% uncertainty interval[UI]: 1.28-3.36). Age-standardized YLD rates for leprosy decreased from 0.09 (95%UI: 0.06-0.13) in 1990 to 0.04 (95%UI: 0.03-0.06) in 2019; the proportional decrease was 55.56% over 30 years. Age-standardized YLDs for HIV and sexually transmitted infections increased by 26% during the same time period. Age-standardized YLDs for non-melanoma skin cancer increased at a much higher rate than melanoma between 1990 and 2019. Dermatitis and scabies continue to have an important role in the burden of skin and subcutaneous disease burden in China. The burden of non-melanoma cell cancer has increased most significantly over the past three decades.

Comparison of the in vitro antibacterial activity of ofloxacin, levofloxacin, moxifloxacin, sitafloxacin, finafloxacin, and delafloxacin against Mycobacterium tuberculosis strains isolated in China.

Objective: The resistance of Mycobacterium tuberculosis (Mtb) to currently available fluoroquinolones (FQs), namely ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), renders the treatment of TB infections less successful. In this study, we aimed to evaluate the susceptibility and intracellular killing assay of Mtb to next-generation FQs in vitro and determine the correlation of FQs resistance and newly detected mutations in gyrB by molecular docking. Methods: Antimicrobial susceptibility test was performed to determine the minimum inhibitory concentrations (MICs) of six FQs, including currently available FQs (OFX, LFX, and MFX) and next-generation FQs, i.e., sitafloxacin (SFX), finafloxacin (FIN) and delafloxacin (DFX) against Mtb clinical isolates obtained in 2015 and 2022, respectively. Quinolone-resistance-determining regions of gyrA and gyrB were subjected to DNA sequencing and the correlation of FQs resistance and new mutations in gyrB were determined by molecular docking. Furthermore, the intracellular antibacterial activity of the six FQs against Mtb H37Rv in THP-1 cells was evaluated. Results: SFX exhibited the highest antibacterial activity against Mtb isolates (MIC90 = 0.25 µg/mL), whereas DFX and OFX exhibited comparable activity (MIC90 = 8 µg/mL). A statistically significant difference was observed among the MICs of the new generation FQs (SFX, P = 0.002; DFX, P = 0.008). Additionally, a marked increase in MICs was found in strains isolated in 2022 compared with those isolated in 2015. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A. Cross-resistance rate between SFX and MFX was 40.6 % (26/64). At a concentration of 1 µg/mL, SFX exhibited high intracellular antibacterial activity (96.6 % ± 1.5 %) against the Mtb H37Rv, comparable with that of MFX at a concentration of 2 µg/mL. Conclusion: SFX exhibits the highest inhibitory activity against Mtb in vitro and THP-1 cell lines, which exhibits partial-cross resistance with MFX. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A.Our findings provide crucial insights into the potential clinical application of SFX and DFX in the treatment of Mtb infections.

Short-Term Alternate Feeding between Terrestrially Sourced Oil- and Fish Oil-Based Diets Modulates the Intestinal Microecology of Juvenile Turbot.

A nine-week feeding trial was conducted to investigate changes in the intestinal microbiota of turbot in response to alternate feeding between terrestrially sourced oil (TSO)- and fish oil (FO)-based diets. The following three feeding strategies were designed: (1) continuous feeding with the FO-based diet (FO group); (2) weekly alternate feeding between soybean oil (SO)- and FO-based diets (SO/FO group); and (3) weekly alternate feeding between beef tallow (BT)- and FO-based diets (BT/FO group). An intestinal bacterial community analysis showed that alternate feeding reshaped the intestinal microbial composition. Higher species richness and diversity of the intestinal microbiota were observed in the alternate-feeding groups. A PCoA analysis showed that the samples clustered separately according to the feeding strategy, and among the three groups, the SO/FO group clustered relatively closer to the BT/FO group. The alternate feeding significantly decreased the abundance of Mycoplasma and selectively enriched specific microorganisms, including short-chain fatty acid (SCFA)-producing bacteria, digestive bacteria (Corynebacterium and Sphingomonas), and several potential pathogens (Desulfovibrio and Mycobacterium). Alternate feeding may maintain the intestinal microbiota balance by improving the connectivity of the ecological network and increasing the competitive interactions within the ecological network. The alternate feeding significantly upregulated the KEGG pathways of fatty acid and lipid metabolism, glycan biosynthesis, and amino acid metabolism in the intestinal microbiota. Meanwhile, the upregulation of the KEGG pathway of lipopolysaccharide biosynthesis indicates a potential risk for intestinal health. In conclusion, short-term alternate feeding between dietary lipid sources reshapes the intestinal microecology of the juvenile turbot, possibly resulting in both positive and negative effects.

Response of Intestinal Microbiota of Tiger Puffer (Takifugu rubripes) to the Fish Oil Finishing Strategy.

The fish oil finishing (FOF) strategy, that is, re-feeding fish with fish oil (FO)-based diet after a certain period of feeding with alternative lipid source-based diets. On tiger puffer, the present study investigated the response of intestinal microbiota to FOF. Fish were fed four diets based on FO, soybean oil, palm oil and beef tallow as lipid sources, respectively, firstly for 50 days (growing-out period), and then fed the FO-based diet for 30 more days (FOF period). The results showed that dietary terrestrially sourced oils impaired the intestinal function in the growing-out period. However, the activities of amylase, trypsin and anti-oxidative enzymes (SOD, CAT, T-AOC), as well as gene expression of inflammatory cytokines (IL-1ß, TNF-α, TGF-ß) and tight junction protein (Claudin4, Claudin7, Claudin18, JAM, ZO-1) in the intestine were significantly recovered by FOF. The 16S rDNA sequencing analysis showed that FOF improved the similarity of bacterial community among the groups. The MetaStat analysis confirmed that FOF regulated the abundance of butyric acid-producing bacteria (Lachnospiraceae, Eubacterium, Butyricicoccus, Clostridium and Roseburia) and bacteria related to digestion and absorption (Sphingomonas, Romboutsia and Brevibacillus). In conclusion, FOF can recover the intestine function. The intestinal microbiota probably participated in and played a key role in the recovery process.

Nosiheptide Harbors Potent In Vitro and Intracellular Inhbitory Activities against Mycobacterium tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) is often associated with poor clinical outcomes. In this study, we evaluated the potential of nosiheptide (NOS) as a new drug candidate for treating Mycobacterium tuberculosis infections, including MDR-TB. The antimicrobial susceptibility testing was performed to determine the MICs of NOS against 18 reference strains of slowly growing mycobacteria (SGM) and 128 clinical isolates of M. tuberculosis. The postantibiotic effects (PAE) and interaction with other antituberculosis drugs of NOS were also evaluated using M. tuberculosis H37Rv. Fifteen out of the 18 tested reference strains of SGM had MICs far below 1 µg/mL. From the 128 M. tuberculosis clinical isolates, the MIC50 and MIC90 were 0.25 µg/mL and 1 µg/mL, respectively; the tentative epidemiological cutoff (ECOFF) was defined at 1 µg/mL. Furthermore, a Lys89Thr mutation was found in one M. tuberculosis isolate with a MIC of NOS >8 µg/mL. After 24 h of incubation, NOS at 1 µg/mL inhibited 25.79 ± 1.22% of intracellular bacterial growth, which was comparable with the inhibitory rate of 25.71 ± 3.67% achieved by rifampin at 2 µg/mL. Compared to rifampicin and isoniazid (INH), NOS had a much longer PAE, i.e., a value of about 16 days. In addition, a partial synergy between NOS and INH was observed. NOS has potent inhibitory activities against M. tuberculosis in vitro as well as in macrophages. Furthermore, the long PAE and partial synergistic effect with INH, in addition to the added safety of long-term use as a feed additive in husbandry, provide support for NOS being a promising drug candidate for tuberculosis treatment. IMPORTANCE This study is aimed at chemotherapy for MDR-TB, mainly to explore the anti-TB activity of the existing chemotherapeutic reagent. We found that NOS has potent inhibitory activities against M. tuberculosis in vitro regardless of the drug-resistant profile. Furthermore, NOS also showed the long PAE and partial synergistic effect with INH and is nontoxic, providing support for its promise as a drug candidate for drug-resistant tuberculosis treatment.

In vitro and intracellular inhibitory activities of nosiheptide against Mycobacterium abscessus.

The high level of inherent drug resistance of Mycobacterium abscessus makes the infection caused by it very difficult to be treated. The objective of this study was to evaluate the potential of nosiheptide (NOS) as a new drug candidate for treating M. abscessus infections. The microplate AlamarBlue assay was performed to determine the minimum inhibitory concentrations (MICs) of NOS for 28 reference strains of rapidly growing mycobacteria (RGM) and 77 clinical isolates of M. abscessus. Time-kill kinetic and post-antibiotic effect (PAE) of NOS against M. abscessus was evaluated. Its bactericidal activity against M. abscessus in macrophages was determined by an intracellular colony numerating assay. NOS manifested good activity against the reference strains of RGM and M. abscessus clinical isolates in vitro. The MICs of NOS against M. abscessus clinical isolates ranged from 0.0078 to 1 µg/ml, and the MIC50 and MIC90 were 0.125 µg/ml and 0.25 µg/ml, respectively. The pattern of growth and kill by NOS against M. abscessus was moderate with apparent concentration-dependent characteristics, and the PAE value of NOS was found to be ~6 h. Furthermore, NOS had low cell toxicity against the THP-1 cell line after 48 h of exposure (IC50 = 106.9 µM). At 4 µg/ml, NOS exhibited high intracellular bactericidal activity against M. abscessus reference strains with an inhibitory rate of 66.52% ± 1.51%, comparable with that of clarithromycin at 2 µg/ml. NOS showed suitable inhibitory activities against M. abscessus in vitro and in macrophages and could be a potential drug candidate to treat M. abscessus infection.

Xpert MTB/RIF Ultra outperformed the Xpert assay in tuberculosis lymphadenitis diagnosis: a prospective head-to-head cohort study.

OBJECTIVES: Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) Ultra (Xpert-Ultra) has shown better sensitivity in comparison with Xpert MTB/RIF (Xpert) in extrapulmonary tuberculosis (TB), whereas the head-to-head comparison of these methods in TB lymphadenitis had barely been performed. METHODS: Patients with undiagnosed lymphadenopathy were recruited prospectively and consecutively, and fine-needle aspiration (FNA) biopsy or lymph node tissue was collected. The specimen was subjected to smear, culture, Xpert, and Xpert-Ultra assays. Culture and/or smear for acid-fast bacilli (AFB) or AFB observed on histopathology were performed as a reference. RESULTS: A total of 106 participants were recruited, including 41 confirmed TB, 33 probable TB, and 32 non-TB lymphadenopathies. The head-to-head comparison for MTB detection showed that Xpert-Ultra produced the highest sensitivity when compared with smear, culture, and Xpert (75.7% vs 5.4 %, 13.5%, and 48.7%). When Xpert-Ultra outcomes were integrated for diagnosis, the percentage of confirmed TB lymphadenitis cases increased from 55.4% (41/74) to 85.1% (63/74). The sensitivities of Xpert-Ultra and Xpert on tissue were 73.6% (95% CI: 59.4-84.3) and 39.6% (95% CI: 26.8-54.0), respectively. The sensitivity of Xpert-Ultra on FNA samples (81.0%, 95% CI: 57.4-93.7) was higher than that of Xpert (71.4%, 95% CI: 47.7-87.8). CONCLUSION: Xpert-Ultra detected significantly more TB lymphadenitis cases than Xpert or culture. This superiority was particularly distinct using lymph node tissue than FNA detection.

Dietary lipid levels affected antioxidative status, inflammation response, apoptosis and microbial community in the intestine of juvenile turbot (Scophthalmus maximus L.).

A nine-week feeding trial was conducted to comprehensively investigate the effects of different levels of dietary lipid on intestinal physiology of juvenile turbot. Three diets with different lipid levels (8%, 12% and 16%) were formulated, which were designated as the low-lipid group (LL), medium-lipid group (ML) and high-lipid group (HL), respectively. Each diet was fed to six replicate tanks, and each tank was stocked with 35 fish. The results revealed that medium dietary lipid (12%) increased the activities of intestinal digestive enzymes and brush border enzymes. Excessive dietary lipid (16%) decreased the intestinal antioxidative enzyme levels and increased the lipid peroxidation pressure. In addition, HL stimulated the occurrence of intestinal inflammation and significantly up-regulated the mRNA expression level of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interferon-γ (IFN-γ) and transforming growth factor-ß (TGF-ß). Dietary LL and HL induced the apoptosis of intestinal epithelial cells. Sequencing of bacterial 16 s rRNA V4 region indicated that the abundance and diversity of intestinal microflora in fish fed with medium lipid diet (12%) were significantly higher than those in other groups, indicating the intestinal microflora ecology in group ML was more balanced. MetaStat analysis indicated that both low- and high-lipid diets significantly reduced the relative abundance of intestinal beneficial bacteria. In conclusion, results of this study demonstrated the sensitivity of intestinal health and microbiota to dietary lipid levels. From the perspective of microecological balance, medium dietary lipid (12%) was more conducive to maintaining the intestinal microflora stability of turbot.