A novel inherited CARD9 deficiency in an otherwise healthy woman with CNS candidiasis.

Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.

Optimization of constructed wetlands on purifying black-odorous water and their potential purification mechanism.

Black-odorous water has become a common and widespread problem in recent decades. In this study, nine constructed wetlands (CWs) with different flow types, filters, plants, and hydraulic loadings were designed according to an orthogonal array (L9 (34), and were used for the purification of black-odorous water in summer and winter. The results showed that CWs are regarded as effective to purify black-odorous water in both seasons. Microbial degradation is the major removal pathway of pollutants in CWs during summer, while the joint effect of biodegradation and adsorption is the main treatment route during winter. Flow type and hydraulic loading appear to be the most important factors impacting the purification performance of CWs, by changing the redox condition of systems and retention time of contaminants, respectively. 'Vertical flow-zeolite filter-high loading' is proposed as the best parameter selection for CWs on the purification of black-odorous water: among them, CWs with vertical flow have better oxygen transport capacity that is conductive to aerobic processes of pollutants, zeolite substrates may adsorb more nitrogen via ion exchange, higher hydraulic loadings can extend the contact time between contaminants and filters, and regulate the water temperature for microbial activity.

[Formulation regularity of traditional Chinese medicine in treatment of sinusitis based on data mining].

Based on the Drugdataexpy and the prescription modern application database, this study explored the formulation regularity of ancient and modern prescriptions for the treatment of sinusitis. The Chinese medicinal prescriptions for the treatment of sinusitis with various syndromes were retrieved from the above databases and the corresponding formulation regularity was investigated by frequency analysis, association rule analysis, and factor analysis. Eighty-seven Chinese medicinal prescriptions were included, involving five syndrome types of sinusitis and 160 Chinese medicine, which were mainly effective in releasing exterior, clearing heat, and tonifying deficiency, and acted on the lung meridian due to cold and warm nature and pungent and bitter flavor or on the spleen meridian due to warm nature and pungent flavor. Seventeen core Chinese medicine were screened out by topological data analysis, including Angelicae Dahuricae Radix, Magnoliae Flos, Glycyrrhizae Radix et Rhizoma, Xanthii Fructus, and Scutellariae Radix. Chinese medicine such as Magnoliae Flos, Angelicae Dahuricae Radix, and Xanthii Fructus were commonly used in the treatment of sinusitis of wind-heat in the lung meridian, while the combination of Glycyrrhizae Radix et Rhizoma, Magnoliae Flos, Angelicae Dahuricae Radix, Chuanxiong Rhizoma, etc. was the key compatibility in treating sinusitis of dampness-heat in the spleen and stomach. Six common factors were extracted from the factor analysis of the above two syndrome types. The findings indicate that the exterior-releasing, heat-clearing, and deficiency-tonifying Chinese medicine with cold and warm nature and pungent flavor are preferential options for the clinical treatment of sinusitis. Treatment should be based on syndrome differentiation and key therapeutic principles should be followed.

Immune reconstitution inflammatory syndrome in non-HIV cryptococcal meningitis: Cross-talk between pathogen and host.

BACKGROUND: Cryptococcal meningitis (CM)-associated immune reconstitution inflammatory syndrome (IRIS) is associated with high mortality, the epidemiology and pathophysiology of which is poorly understood, especially in non-HIV populations. OBJECTIVES: We aim to explore the incidence, clinical risk factors, immunological profiles and potential influence of leukotriene A4 hydroxylase (LTA4H) on non-HIV CM IRIS populations. METHODS: In this observational cohort study, 101 previously untreated non-HIV CM patients were included. We obtained data for clinical variables, 27 cerebrospinal fluid (CSF) cytokines levels and LTA4H genotype frequencies. Changes of CSF cytokines levels before and at IRIS occurrence were compared. RESULTS: Immune reconstitution inflammatory syndrome was identified in 11 immunocompetent males, generating an incidence of 10.9% in non-HIV CM patients. Patients with higher CrAg titres (> 1:160) were more likely to develop IRIS, and titre of 1:1280 is the optimum level to predict IRIS occurrence. Baseline CSF cytokines were significantly higher in IRIS group, which indicated a severe host immune inflammation response. Four LTA4H SNPs (rs17525488, rs6538697, rs17525495 and rs1978331) exhibited significant genetic susceptibility to IRIS in overall non-HIV CM, while five cytokines were found to be associated with rs1978331, and baseline monocyte chemotactic protein 1 (MCP-1) became the only cytokine correlated with both IRIS and LTA4H SNPs. CONCLUSIONS: Our study suggested that non-HIV CM patients with high fungal burden and severe immune inflammation response were more likely to developed IRIS. LTA4H polymorphisms may affect the pathogenesis of IRIS by regulating the level of baseline CSF MCP-1.

Removal efficiency, kinetic, and behavior of antibiotics from sewage treatment plant effluent in a hybrid constructed wetland and a layered biological filter.

Sewage treatment plant (STP) is the major point source of antibiotic contamination, yet the advanced treatment of antibiotic polluted STP effluent has not been given necessary attention. This study is conducted to evaluate the removal efficiency, kinetic, and behavior of sulfonamides, quinolones, tetracyclines, and macrolides antibiotics from STP effluent in a hybrid constructed wetland (HCW) and a layered biological filter (LBF) at different hydraulic loading rates (HLRs). The results showed that the removal efficiency of antibiotics in all the HLRs was ranked as follow: quinolones of HCW (70-95%) > macrolides of HCW (58-77%) > tetracyclines of both systems (59-67%) > quinolones of LBF (28-64%) > macrolides of LBF (13-25%) > sulfonamides of both systems (<0%). The optimal HLR is 1.0 m/day for quinolones and 2.0 m/day for tetracyclines-macrolides in the HCW, and 6.4 m/day for quinolones-tetracyclines in the LBF, respectively. Although HCW performed better on the removal of most antibiotics, LBF exhibited stronger total loading toleration and higher removal loading ability to antibiotics. Among them, quinolones were markedly removed by multiple effect of substrate adsorption, microbial anaerobic degradation, and photolysis in the HCW (planted), and by filter sorption and interception in the LBF (unplanted); adsorption is the dominant elimination approach for tetracyclines in both systems; plant uptake plays a significant role on the removal of macrolides in the HCW.

Genetic polymorphisms of transient receptor potential melastatin 1 correlate with voriconazole-related visual adverse events.

BACKGROUND: Causes of voriconazole-related visual adverse events (VVAE) remained controversial. OBJECTIVES: We aimed to explore the relationship between voriconazole serum concentrations and VVAE as well as the potential influence of transient receptor potential melastatin 1 (TRPM1) on VVAE. PATIENTS/METHODS: This prospective observational cohort study was done in two stages. Patients who received voriconazole for invasive fungal diseases were consecutively enrolled. Correlations between voriconazole trough levels and VVAE were explored in 76 patients. Genotyping was further conducted for 17 tag SNPs of TRPM1 in a larger population of 137 patients. Genotype distributions were compared between patients with and without VVAE. RESULT: Of the 76 patients, a total of 229 steady-state voriconazole trough levels were evaluated, 69.9% of which were within the target range (1-5.5 mg/L). No correlations were found between voriconazole trough levels and VVAE. Of the total 137 patients, VVAE occurred in 37 (27.0%) patients, including visual hallucination (13.9%, 19/137) and visual disturbances (19.0%, 26/137). Significant difference in TRPM1 genotype distribution was only observed in patients with visual hallucination but not with visual disturbances. We found that rs890160 G/T genotype was under-presented (OR, 0.11; 95% CI, 0.01-0.84; P = .011) and rs1378847 C/C genotype was more frequently detected (OR, 8.89; 95% CI, 1.14-69.02; P = .013) in patients with visual hallucination when compared with those without. CONCLUSION: Transient receptor potential melastatin 1 was genetically associated with voriconazole-related visual hallucination. The correlation was failed to found between voriconazole trough levels and VVAE.

Global recurrence rates in diabetic foot ulcers: A systematic review and meta-analysis.

Recurrence rates of diabetic foot ulcers vary widely in the published literature. The aim of this systematic review is to estimate recurrence rates of diabetic foot ulcers. We did a PubMed search and performed a review of reference lists for studies reporting recurrence of diabetic foot ulcers. The weighted relative risk (RR) and corresponding 95% confidence interval (CI) for recurrence was estimated. Forty-nine studies reporting recurrence of diabetic foot ulcers were included. A pooled estimate for recurrence rate was 22.1% per person-year (py) (95% CI, 19.0-25.2%). Recurrence rate was 24.9% per py in Europe (95% CI, 20.0%-29.7%), 17.8% per py in North America (95% CI, 12.7%-22.9%), 16.9% per py in Africa (95% CI, 4.7%-29.0%), and 17.0% per py in Asia (95% CI, 11.1%-23.0%). Turkey had the highest recurrence rate of 44.4% per py (95% CI, 24.9%-63.9%), and Bangladesh had the lowest of 4.3% per py (95% CI, 2.3%-6.3%). Recurrence rates of diabetic foot ulcers before 2002, between 2002 and 2008, and after 2008 were 22.2% per py (95% CI, 17.6%-26.8%), 21.9% per py (95% CI, 17.0%-26.8%), and 21.8% per py (95% CI, 16.3%-27.2%), respectively. Recurrence rates of diabetic foot ulcers are high. Recurrence rates vary widely in different regions and have decreased recently. More attention towards recurrence of diabetic foot ulcers is urgently required.

Biodegradation of sulfamethazine by an isolated thermophile-Geobacillus sp. S-07.

Sulfamethazine (SM2) is an antimicrobial drug that is frequently detected in manure compost, is difficult to degrade at high temperatures and is potentially threatening to the environment. In this study, a thermophilic bacterium was isolated from the activated sludge of an antibiotics pharmaceutical factory; this bacterium has the ability to degrade SM2 at 70 °C, which is higher than the traditional manure composting temperature. The strain S-07 is closely related to Geobacillus thermoleovorans based on its 16S rRNA gene sequence. The optimal conditions for the degradation of SM2 are 70 °C, pH 6.0, 50 rpm rotation speed and 50 mL of culture volume. More than 95% of the SM2 contained in media was removed via co-metabolism within 24 h, which was a much higher percentage than that of the type strain of G. thermoleovorans. The supernatant from the S-07 culture grown in SM2-containing media showed slightly attenuated antibacterial activity. In addition, strain S-07 was able to degrade other sulfonamides, including sulfadiazine, sulfamethoxazole and sulfamerazine. These results imply that strain S-07 might be a new auxiliary bacterial resource for the biodegradation of sulfonamide residue in manure composting.

Zinc finger A20 and NF-κB correlate with high-risk human papillomavirus of squamous cell carcinoma patients.

Genital human papillomavirus (HPV) is associated with the development of cutaneous malignant tumors, and differences in HPV subtypes are found in several cancers by histology. NF-κB is persistently activated in most cancers and confers a survival advantage to cancer cells, while A20 is a critical negative regulator of NF-κB and is an important tumor suppressor inactivated in B cell lymphomas. This study was undertaken to identify HPV types in cutaneous squamous cell carcinoma (SCC) as well as to determine whether the crosstalk of A20/NF-κB was involved in HPV-induced SCC. Overall, HPV positivity was observed to be 66.2 %, with HPV16 being most common followed by infection with HPV18. Out of 43 HPV-positive samples, 35 samples were positive for one or more high-risk HPV (HR-HPV) types, suggesting a high association of SCC with HR-HPV infection, while only five HPV infections were detected in 21 normal skin samples and low-risk HPV (LR-HPV) infection was the most common. Both A20 and NF-κB were overexpressed in HPV-positive SCC samples (56 vs 87.4 %) and were closely correlated with TNM stage and lymph node transfer, respectively. More interestingly, the expression of A20 and NF-κB was much higher in HR-HPV samples than in LR-HPV samples. These results suggest that the crosstalk of A20 and NF-κB may contribute to HR-HPV-associated tumor growth and metastasis of SCC and may be a novel therapeutic target for SCC in the future.

[Advance in studies on anti-inflammatory and immunoregulatory monomers of Tripterygium wilfordii].

Tripterygium wilfordii has complex chemical components. To study and summarize the advance in studies on the anti-inflammatory and immunoregulatory activities and toxicology of known monomers of T. wilfordii, the pertinent literatures related to the studies on the pharmacology, toxicology and pharmacokinetics of T. wilfordii over past 30 years were searched. According to the findings, more than ten anti-inflammatory and immunoregulatory monomers were found in T. wilfordii. The pharmacology and toxicology of wilforidine, triptolidenol, triptonide, demethylzeylasteral shall be further studied.

Purification of the secondary treatment tail water for wastewater reclamation by integrated subsurface-constructed wetlands.

A whole-year investigation of full-scale integrated subsurface-constructed wetlands (ISCWs) was carried out to purify the tail water from a wastewater treatment plant (WWTP) for wastewater reclamation under four plant species, four hydraulic loading rates (HLRs), and four seasons. The results showed that ISCWs were effective for the purification of WWTP discharge, with the average removal efficiencies of COD, NH4+-N, TN, and TP being 48%, 49%, 9%, and 30%, respectively. Typical pollutant concentrations in the treated effluent of ISCWs were 8.19 mg/L COD, 1.76 mg/L NH4+-N, 11.57 mg/L TN, and 0.36 mg/L TP, which met most of the water quality standards for reusing recycling water. Emergent plants with well-developed root systems may be capable of promoting the decontamination of ISCWs. Seasonal change played an important role in the treatment process: the removal of phosphorus by plant uptake and microbial utilization was more active in the warm season and the co-occurrence of organic degradation and nitrification, whereas the cold season is conducive to exothermic adsorption process of pollutants to substrates. Properly increasing the HLRs may improve the availability of ISCWs according to the requirement of effluent quality. Furthermore, the C/N ratio might be the key factor for the purification effect of ISCWs, because the COD level of WWTP discharge may change the process of NH4+-N biotransformation.

A three-year study on the treatment of domestic-industrial mixed wastewater using a full-scale hybrid constructed wetland.

Three full-scale constructed wetlands (CWs), namely vertical flow (VFCW), surface flow (SFCW), and horizontal flow (HFCW) systems, were combined in a series process to form a hybrid CW, which was used for the treatment performance of domestic-industrial mixed wastewater and investigated over a three-year period. The hybrid CW demonstrated that it is effective and stable during the long-term treatment of high-loading mixed wastewater under different operation years, season changes, and technology processes, with the average removal efficiencies of suspended solids, chemical oxygen demand, biological oxygen demand, total nitrogen, ammonia nitrogen, nitrate nitrogen, and total phosphorous being 84, 40, 54, 54, 70, 40, and 46%, respectively. The effluent quality of the hybrid CW reached the highest discharge standard for wastewater treatment plants. First, a variety of pollutants from the mixed wastewater were effectively removed in the subsurface processes (VFCW and HFCW) via substrate adsorption and degradation of the attached biofilm. The higher dissolved oxygen content and oxygen transfer capacity values in the VFCW were favourable for the occurrence of aerobic pathways (such as nitrification and inorganic phosphorus oxidation). In addition, with the large consumption of oxygen in the previous process, the oxygen-enriching capacity of the SFCW processes, provided aerobic potential for the next stage. In particular, the plant debris in the SFCW temporarily increased the organics and suspended solids, further increasing the C/N ratio, which was beneficial for denitrification as the main nitrogen removal pathway in the HFCW.

Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.

Backgrounds: The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons. Methods: This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework. Results: Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups. Conclusion: In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.

Safety of sodium-glucose transporter 2 (SGLT-2) inhibitors in patients with type 2 diabetes: a meta-analysis of cohort studies.

Aims: This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower limb amputation (LLA), urinary tract infections (UTI), genital tract infections (GTI), bone fracture, and hypoglycemia in cohort studies. Methods: A systematic search was conducted in the PubMed and Embase databases to identify cohort studies comparing the safety of SGLT-2i versus other glucose-lowering drugs (oGLD) in patients with type 2 diabetes mellitus (T2DM). The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary endpoints were DKA and LLA, while secondary endpoints included UTI, GTI, bone fracture, and hypoglycemia. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Results: A total of 9,911,454 patients from 40 cohort studies were included in the analysis. SGLT-2i use was associated with a higher risk of DKA (HR: 1.21, 95% CI: 1.07-1.38, p = 0.003) and GTI (HR: 2.72, 95% CI: 2.48-2.98, p < 0.01). However, it was not associated with an increased risk of LLA (HR: 1.06, 95% CI: 0.92-1.23, p = 0.42), UTI (HR: 0.99, 95% CI: 0.89-1.10, p = 0.83), or bone fracture (HR: 0.99, 95% CI: 0.94-1.04, p = 0.66). Furthermore, SGLT-2i was associated with a reduced risk of hypoglycemia. Furthermore, compared to dipeptidyl peptidase 4 inhibitors, SGLT-2i as a class and individually was associated with an increased risk of DKA. Canagliflozin specifically increased the risk of LLA (HR: 1.19, 95% CI: 1.04-1.36, p = 0.01). The subgroup analysis suggested that SGLT-2i increased the risk of LLA among patients with a history of cardiovascular disease. Conclusion: SGLT-2i versus oGLD was associated with a similar occurrence of LLA, UTI, and bone fracture. However, SGLT-2i was associated with a higher risk of DKA and GTI than oGLD. These findings provide valuable information on the safety profile of SGLT-2i in patients with T2DM and can help inform clinical decision-making.

Effects of cadmium exposure on intestinal microflora of Cipangopaludina cathayensis.

As one of the most environmentally toxic heavy metals, cadmium (Cd) has attracted the attention of researchers globally. In particular, Guangxi, a province in southwestern China, has been subjected to severe Cd pollution due to geogenic processes and anthropogenic activities. Cd can be accumulated in aquatic animals and transferred to the human body through the food chain, with potential health risks. The aim of the present study was to explore the effects of waterborne Cd exposure (0.5 mg/L and 1.5 mg/L) on the intestinal microbiota of mudsnail, Cipangopaludina cathayensis, which is favored by farmers and consumers in Guangxi. Gut bacterial community composition was investigated using high-throughput sequencing of the V3-V4 segment of the bacterial 16S rRNA gene. Our results indicated that C. cathayensis could tolerate low Cd (0.5 mg/L) stress, while Cd exposure at high doses (1.5 mg/L) exerted considerable effects on microbiota composition. At the phylum level, Proteobacteria, Bacteroidetes, and Firmicutes were the dominant phyla in the mudsnail gut microbiota. The relative abundances of Bacteroidetes increased significantly under high Cd exposure (H14) (p < 0.01), with no significant change in the low Cd exposure (L14) treatment. The dominant genera with significant differences in relative abundance were Pseudomonas, Cloacibacterium, Acinetobacter, Dechloromonas, and Rhodobacter. In addition, Cd exposure could significantly alter the pathways associated with metabolism, cellular processes, environmental information processing, genetic information processing, human diseases, and organismal systems. Notably, compared to the L14 treatment, some disease-related pathways were enriched, while some xenobiotic and organic compound biodegradation and metabolism pathways were significantly inhibited in the H14 group. Overall, Cd exposure profoundly influenced community structure and function of gut microbiota, which may in turn influence C. cathayensis gut homeostasis and health.

Characterization of Gut Microbiome in the Mud Snail Cipangopaludina cathayensis in Response to High-Temperature Stress.

The mud snail Cipangopaludina cathayensis is a widely distributed species in China. Particularly in Guangxi province, mud snail farming contributes significantly to the economic development. However, global warming in recent decades poses a serious threat to global aquaculture production. The rising water temperature is harmful to aquatic animals. The present study explored the effects of high temperature on the intestinal microbiota of C. cathayensis. Snail intestinal samples were collected from the control and high-temperature groups on days 3 and 7 to determine the gut microbiota composition and diversity. Gut bacterial community composition was investigated using high-throughput sequencing of the V3-V4 region of bacterial 16S rRNA genes. Our results suggested that thermal stress altered the gut microbiome structure of C. cathayensis. At the phylum level, Proteobacteria, Bacteroidetes, and Firmicutes were dominant in C. cathayensis gut microbiota. The T2 treatment (32 ± 1 °C, day 7) significantly decreased the relative abundance of Firmicutes, Actinobacteria, and Deinococcus-Thermus. In T2, the abundance of several genera of putatively beneficial bacteria (Pseudomonas, Aeromonas, Rhodobacter, and Bacteroides) decreased, whereas the abundance of Halomonas-a pathogenic bacterial genus-increased. The functional prediction results indicated that T2 treatment inhibited some carbohydrate metabolism pathways and induced certain disease-related pathways (e.g., those related to systemic lupus erythematosus, Vibrio cholerae infection, hypertrophic cardiomyopathy, and shigellosis). Thus, high temperature profoundly affected the community structure and function of C. cathayensis gut microbiota. The results provide insights into the mechanisms associated with response of C. cathayensis intestinal microbiota to global warming.

[Prevalence of diabetes mellitus and impaired fasting glucose of health check-up in a sanatorium of Shanghai in 2003 and 2010].

OBJECTIVE: To examine the prevalence changes of diabetes mellitus (DM) and impaired fasting glucose (IFG) from 2003 to 2010 in the health check-up subjects in Shanghai. METHODS: Health check-up subjects were divided into ten groups by sex and each 5 years old, and the prevalence of crude DM, crude IFG were calculated first. According to Chinese sex and age structure of China Population Statistics Yearbook 2006, sex and age standardized DM and standardized IFG were computed. RESULTS: In the same year, the prevalences of crude DM and IFG increased with increasing age for both male and female, reached the summit at 60 - 69 age group, when at ≥ 70 age group, they had a down trend and were still at higher level. The prevalences of crude DM were 3.99% (986/24 699) in male and 1.61% (176/10 948) in female in 2003, and were 7.85% (3366/42 899) and 2.55% (531/20 820) in 2010. The prevalences of crude IFG were 9.97% (2462/24 699) in male and 5.88% (644/10 948) in female in 2003, and were 30.96% (13 283/42 899) and 17.16% (3573/20 820) in 2010. The prevalences of age standardized DM in 2003 and 2010 were 3.89% and 6.90% for male (χ(2) = 371.89, P < 0.01), 2.12% and 3.23% for female (χ(2) = 29.32, P < 0.01), respectively. The prevalences of age standardized IFG in 2003 and 2010 were 9.51% and 28.55% (χ(2) = 3865.56, P < 0.01) for male, 6.97% and 17.88% (χ(2) = 790.81, P < 0.01) for female. The prevalences of age and sex standardized DM were 3.00% and 5.05% (χ(2) = 385.39, P < 0.01), and prevalences of age and sex standardized IFG were 8.23% and 23.17% (χ(2) = 4480.21, P < 0.01). CONCLUSION: From 2003 to 2010, prevalences of DM and IFG had increased greatly. It concluded that first-level prevention of DM for health check-up subjects should start from youth, and should lay emphasis on population of IFG, especially for male.

A Case of Cutaneous Rosai-Dorfman Disease Treated by Intralesional Injections of Glucocorticoid.

A 45-year-old male presented with painless reddish-brown plaques and nodules that had infiltrated his shoulder and back for 3 months. From the clinical manifestations and histopathological findings, the patient was diagnosed with cutaneous Rosai-Dorfman disease. Intralesional injections of betamethasone (trade name: diprospan) were recommended and the lesions improved significantly after three treatments.

Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis.

BACKGROUND AND AIMS: Glucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by sodium-glucose cotransporter 2 inhibitors (SGLT-2i) has been confirmed by some large-scale randomized controlled studies (RCTs) and systematic reviews of RCTs, but exact indicators of cardiovascular risk remained controversial. Whether consistent results can be obtained in clinical practice is unclear. Therefore, in this meta-analysis, we analyzed the real-world effect of SGLT-2i on cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM). METHODS: We did a real-world systematic review and meta-analysis of cardiovascular outcome of SGLT-2i in patients with T2DM. We searched PubMed and Embase for trials published up to October 23, 2019. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The primary outcome was MACE and all-cause mortality (ACM). Secondary outcomes were hospitalization for heart failure (HHF), atrial fibrillation (AF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), unstable angina (UA), heart failure (HF). Odds ratio (OR) with 95% CIs were pooled across trials, and cardiovascular outcomes were stratified by baseline incidence of cardiovascular disease (CVD), usage rate of cardiovascular benefit drug, follow-up period and region. RESULTS: Fourteen trials enrolling 3,157,259 patients were included. SGLT-2i reduced MACE (OR, 0.71; 95% CI 0.67,0.75, P<0.001) and ACM (OR, 0.53; 95% CI 0.49,0.57, P<0.001) compared to other glucose lowering drugs (oGLD). Compared with oGLD, SGLT-2i had significantly lowered the risk of HHF (OR, 0.56; 95% CI 0.46,0.68, P<0.001), MI (OR, 0.77; 95% CI 0.73,0.81, P<0.001), stroke (OR, 0.75; 95% CI 0.72,0.78, P<0.001), CVM (OR, 0.58; 95% CI 0.49,0.69, P<0.001) and HF (OR, 0.56; 95% CI 0.48,0.67, P<0.001), but there was no benefit from UA or AF. SGLT-2i significantly reduced the risk of severe hypoglycemia (OR, 0.78; 95% CI 0.69,0.90, P<0.001) and lower limb amputation (OR, 0.83; 95% CI 0.71,0.98, P<0.001), but it may increase the risk of diabetic ketoacidosis. Subgroup analysis showed SGLT-2i reduced the risk of MACE, ACM, HHF, MI, stroke, CVM and HF with a similar benefit regardless of the incidence of CVD was (20-30)% or < 15%, (15-30)% or <15% have been treated with GLP-1 receptor agonists (GLP-1RA), >80% or <70% have been treated with statins or both GLP-1RA and statins. SGLT-2i reduced the risk of ACM in low-risk population (P<0.001). No inconsistencies were found when stratification was performed at 1 or (3-4) years of follow-up except for BKA followed up for 1 year. SGLT-2i showed similar cardiovascular benefits in the Nordic countries, Asia and the United States. CONCLUSIONS: The predominant impact of SGLT-2i is on cardiovascular outcome driven predominantly by reduction in MACE, ACM, HHF, MI, stroke, CVM, HF, but not UA or AF. SGLT-2i has robust benefits on reducing MACE, ACM, HHF, MI, stroke, CVM and HF regardless of a history of usage rate of GLP-1RA and/or statins and /or metformin. SGLT-2i does not increase the risk of severe hypoglycemia and lower limb amputation.