[Recommendations for the diagnosis and treatment of rheumatic fever in China].

Rheumatic fever is an autoimmune disease characterized by recurring acute or chronic systemic connective tissue inflammation caused by group A streptococcal infection in the throat. Although rheumatic fever is common in China, there is a lack of standardized criteria for the diagnosis and treatment of this condition. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association developed standardized criteria for the diagnosis and treatment of this disease in China. The aim was to standardize rheumatic fever diagnosis methods, treatment opportunities, and strategies for both short-and long-term treatment, so as to reduce irreversible damage and improve prognosis.

Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients, but excluding emergency, cardiothoracic, cerebral and endoscopic sinus cases. PATIENTS AND METHODS: A total of 40 eligible patients were randomly assigned to HSK3486 (n = 30) or propofol (n = 10) dosage groups in a ratio of 3:1. Drugs were administered as a bolus injection of 0.4 mg/kg (HSK3486) or 2.0 mg/kg (propofol) for induction, followed by maintenance infusion with the same anesthetic. An additional 6 non-randomized patients received propofol (2.0 mg/kg) for induction and were given HSK3486 for maintenance. RESULTS: The primary efficacy endpoint - the success rate of anesthesia maintenance - was 100% in the 3 arms. The secondary efficacy endpoints included times from discontinuation of HSK3486 or propofol maintenance to full alertness, respiratory recovery, extubation and reaching the goal of the Aldrete score. Also, the proportion of patients who constantly maintained BIS40-60 or those with a period of BIS40-60 during maintenance anesthesia showed no significant difference in the HSK3486 and propofol groups (all p > 0.05). Patients who received HSK3486 exhibited a higher satisfaction score from anesthesiologists during the induction period (p = 0.024). The occurrence and types of treatment-emergent adverse events were similar among the 3 arms, both with a severity of grade 1 or 2. Drug-related hypotension occurred in 14 (46.7%) and 7 (70.0%) patients treated with HSK3486 and propofol, respectively. CONCLUSIONS: HSK3486 exhibited good efficacy for the induction and maintenance of general anesthesia and was well tolerated by patients who underwent elective surgery.

[Diagnosis and progress in the progressive symmetric erythrokeratodermia].

Progressive symmetric erythrokeratodermia (PSEK) comprises a group of clinically and genetically heterogeneous diseases. Previous research have identified GJB3 and GJB4 as the leading genetic causes of this disorder. With the rapid development of genetics, GJA1, KDSR, KRT83 and TRPM4 have been identified as the new causative genes for PSEK, leading to a further understanding of its clinical features and genetic mechanisms. It's worth noting that Nagashima-type palmoplantar keratosis was often misdiagnosed as PSEK by our domestic dermatologists. Due to the identification of SERPINB7 as the causative gene of Nagashima-type palmoplantar keratosis recently, differentiation between the two disorders could be easily distinguished.

[Epidemiologic characteristics and strategies on prevention and control of sexually transmitted human immunodeficiency virus/acquired immunodeficiency syndrome in China].

At present, sexual route is the main transmission route of AIDS in China, and its role in the process of AIDS epidemic has been evolving. Various modes of transmission in sexual transmission and the prevention and control strategies adopted by China have also been changing. This paper mainly summarizes the epidemic characteristics of different periods and different modes of transmission of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in China in recent years. The strategies of prevention and control were described from seven aspects, including health education, promotion of condom use, expanded testing, HIV/AIDS antiviral treatment, pre-exposure prophylactic medication, post-exposure prophylactic medication, social organization participation and sexually transmitted diseases prevention and control. Only when innovative and targeted measures according to the evolution of the HIV/AIDS epidemic and various specific methods are complemented by each other, can the transmission of HIV/AIDS through sexual route be effectively prevented and controlled.

[Value of double contrast-enhanced ultrasound QontraXt three-dimensional pseudocolor quantitative analysis to therapeutic effect evaluation of preoperative neoadjuvant chemotherapy in advanced gastric cancer patients].

Objective: To investigate the value of tumor perfusion parameter measured by using double contrast-enhanced ultrasound (DCEUS) QontraXt three-dimensional pseudocolor quantitative analysis to the therapeutic effect evaluation of preoperative neoadjuvant chemotherapy (NAC) in advanced gastric cancer (AGC) patients. Methods: Eighty-nine AGC patients underwent 3 cycles of preoperative NAC (XELOX) followed by complete resection of lesion. The DCEUS QontraXt three-dimensional pseudocolor was performed one or two weeks before the NAC and operation were applied, respectively. The peak enhancement (PE), time to peak (TP), sharpness of the bolus (ß) and area under the enhancement curve (AUC) of primary gastric tumor were measured by QontraXt three-dimensional pseudocolor quantitative analysis. These DCEUS parameters between respond and non-respond groups before and after NAC therapy were compared. The prediction accuracy of DCEUS to the therapeutic effect evaluation of preoperative NAC was determined by the receive operating characteristic (ROC) curves. Results: Among 89 AGC patients, 52 patients responded to NAC therapy, while 37 patients resisted to NAC therapy. Twelve cases in respond group and 26 cases in non-respond group were mucinous carcinoma. Forty cases in respond group and 11 cases in non-respond group were non-mucinous carcinoma (P<0.05). In responder group, the PE and TP before NAC were (53.7±9.3)% and (14 521±2 667) ms, and (32.2±5.5)% and (17 235±1 898) ms after NAC. The ratio of changes of PE (ΔPE) and TP (ΔTP) were 0.43±0.17 and 0.36±0.14, respectively. In non-respond group, the PE and TP before NAC were (54.4±7.2)% and (13 869±3 247) ms, and (45.3±6.1)% and (15 127±1 423) ms after NAC therapy. The ratio of ΔPE and ΔTP were 0.24±0.20 and 0.22±0.12. The PE and TP after NAC, the ratio of ΔPE and ΔTP were significant different among these two groups (all of P<0.05). The ROC curves showed that the ratio of ΔPE in assessing the respond of gastric cancer patients to NAC was superior compared to other parameters (AUC=0.784, P=0.004). The optimal cut-off value of the ratio of ΔPE was 24% and its sensitivity and specificity to the therapeutic effect evaluation of NAC in gastric cancer were 82.7% and 64.9%. Conclusion: DCEUS QontraXt three-dimensional pseudocolor quantitative analysis might be a novel, noninvasive and reliable method to evaluate the therapeutic effect of preoperative NAC in AGC patients.

[Effect of febuxostat on epithelial-to-mesenchymal transition of kidney tubules, serum interleukin-6 and transforming growth factor ß(1) in hyperuricemic rats].

Objective: To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF)ß(1) in hyperuricemic rats. Methods: Forty male SD rats were divided into 4 groups: normal control group (NC group), oteracil potassium group (OP group), oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group). Each group had 10 rats and balanced in body weights. To induce hyperuricemia, rats were given oteracil potassium by gastric gavage once a day for eight weeks. Rats in OF group and OB group were given either febuxostat or benbromarone starting with oteracil potassium, and rats in NC group was given saline only. Blood samples were taken before, and at the end of 4 and 8 weeks of the treatments and serum uric acid, creatinine, blood usea nitrogen(BUN), IL-6 and TGFß(1) contents were measured at each time point. Renal pathological changes were observed via HE and Masson staining, and the expression of α-SMA and E-cadherin were detected by immunohistochemistry. Results: Compared with those in NC group, the levels of serum uric acid, creatinine, BUN, IL-6 and TGFß(1) in the another three groups were increased significantly (all P<0.01). However, the IL-6 and TGFß(1) contents in OF group were much lower than those in OP group (P<0.01). HE and Masson staining showed that OF group had less damage and tubulointerstitial fibrosis than OP group and OB group (P<0.01). Moreover, the expression of α-SMA was significantly down-regulated (P<0.01) and that of E-cadherin was significantly up-regulated in OF group compared with those in OP group. Conclusion: Febuxostat treatment significantly inhibited EMT and reduced the levels of IL-6 and TGFß(1) in hyperuricemia rats.

MicroRNA-135b inhibits odontoblast-like differentiation of human dental pulp cells by regulating Smad5 and Smad4.

AIM: To investigate the function of miRNAs in odontoblast-like differentiation of human dental pulp cells (hDPCs). METHODOLOGY: Integrated comparative miRNA microarray profiling was used to determine the differential miRNAs expression in odontoblast-like differentiation of hDPCs. The abundance of microRNA-135b (miR-135b) was measured by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Bioinformatic analyses combined with luciferase assays were utilized to identify the targets interacting with miR-135b. Overexpression of miR-135b was performed to investigate the role and mechanism in odontoblast-like differentiation of hDPCs. Statistical analysis was performed by one-way analysis of variance (anova) or Student's t-test. RESULTS: Thirty-six differentially expressed microRNAs in odontoblast-like differentiation of hDPCs were identified. MiR-135b expression was significantly downregulated during hDPCs differentiation (P < 0.05). In addition, miR-135b was able to bind to the 3'-UTR of the Smad5 and Smad4 and repressed these two genes expression (P < 0.05). Furthermore, overexpression of miR-135b suppressed odontoblast-like differentiation of hDPCs and attenuated the expression of Smad5 and Smad4 (P < 0.05). CONCLUSIONS: These observations indicated a potential role of miR-135b in mediating odontoblast-like differentiation of hDPCs and inhibition of miR-135b might be a promising therapeutic way to facilitate dentine tissue engineering.

Identification of LCK mutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma.

BACKGROUND: Inherited epidermodysplasia verruciformis (EV) is a rare skin disorder characterized by susceptibility to specific types of human papilloma virus (HPV) and is strongly associated with skin carcinomas. Inactivating mutations in EVER1/EVER2 account for most cases of EV. However, more phenotypes related to but distinct from EV have been reported with an immunodeficiency state but without EVER1/EVER2 mutation, and the genetic basis for these atypical EV cases is poorly understood. OBJECTIVES: To identify the causative gene responsible for three siblings affected by atypical EV but without EVER1/EVER2 mutation. METHODS: Whole-exome sequencing followed by Sanger sequencing was performed to identify the gene responsible for the patients with atypical EV enrolled in our study. RESULTS: A homozygous splicing mutation was detected in LCK (c.188-2A>G). This mutation resulted in an exon 3 deletion T lymphocyte-specific protein tyrosine kinase isoform, which further led to frameshift mutation and subsequent mRNA decay. CONCLUSIONS: We demonstrate a novel mutation in LCK in a family affected by atypical EV with T-cell defects, HPV infection and virus-induced malignancy, providing new clues in the understanding of host defences against HPV and better genetic counselling of patients with the EV phenotype.

Sputum bacteriology in steady-state bronchiectasis in Guangzhou, China.

BACKGROUND: The impact of potentially pathogenic micro-organisms (PPMs) on Chinese patients with steady-state bronchiectasis is unknown. METHODS: Peripheral blood and sputum were sampled to determine inflammatory markers and sputum bacterial density. Spirometry and diffusing capacity were measured. Quality of life was assessed using the St George's Respiratory Questionnaire. RESULTS: Of 144 patients with steady-state bronchiectasis, Pseudomonas aeruginosa was isolated in 44 cases (30.6%). Compared with other PPMs, P. aeruginosa had a more pronounced influence on airway inflammation and spirometry, but not on systemic inflammation or quality of life. The impact of PPMs other than P. aeruginosa on clinical indices was similar. Bacterial density was not correlated with most clinical parameters. Factors associated with PPM isolation included bronchiectasis symptoms for ⩾ 10 years (OR 2.13) and ⩾ 4 bronchiectatic lobes (OR 2.82). Having ⩾ 4 exacerbations within 2 years (OR 2.18) and cystic bronchiectasis (OR 2.23) was associated with the colonisation of PPMs, i.e., isolating an identical PPM on at least two occasions within 1 year. CONCLUSION: In patients with steady-state bronchiectasis in Guangzhou, P. aeruginosa is the most common organism causing heightened airway inflammation and poor lung function. PPM isolation or colonisation should be suspected in case of longer duration of symptoms, multilobar bronchiectasis, frequent exacerbation and cystic bronchiectasis.

Recurrent duplication mutation in HRAS causing mild Costello syndrome in a Chinese patient.

Costello syndrome (CS; OMIM 218040) is caused by heterozygous germline mutations of HRAS (OMIM 190020).We report on a patient with sporadic CS presenting with characteristic craniofacial dysmorphism, congenital cardiopulmonary disorders, intellectual impairment, and skin abnormalities manifesting as loose redundant skin of the hands and feet, acanthosis nigricans, multiple naevi and hypotrichosis. Using Sanger sequencing for the case-parents trio, we detected a de novo insertion mutation (c.187_207dup) in HRAS, which was predicted to result in duplication of amino acids 63-69 (p.E63_D69dup). This mutation was recently described in a mild case of CS, with hyperactivation of HRAS and disrupted capacity to respond to incoming signals. Our study delineates the detailed clinical features associated with this noncanonical HRAS mutation and further expands the phenotypic spectrum of CS.

Validation of the Mandarin Chinese version of the Leicester Cough Questionnaire in bronchiectasis.

BACKGROUND: The Leicester Cough Questionnaire (LCQ) has been validated for assessing cough-specific health status in bronchiectasis. We translated the LCQ into Mandarin Chinese and investigated its validity, reliability and responsiveness. METHODS: The LCQ was translated into Mandarin Chinese using the forward-backward translation procedure. A total of 144 out-patients completed the Mandarin Chinese version of the LCQ (LCQ-MC), the Hospital Anxiety and Depression Scale (HADS) and the St George's Respiratory Questionnaire. Reassessments were performed during exacerbations and at 6 months. Concurrent validation, internal consistency, repeatability and responsiveness were determined. RESULTS: Minor cultural adaptations were made to the wording of LCQ-MC. No other difficulties were found during the translation process, with all items easily adapted to acceptable Mandarin Chinese. The questionnaire was not changed in terms of content layout and the order of the questions. In cognitive debriefing interviews, participants reported that the questionnaire was acceptable, relevant, comprehensive and easy to complete. The LCQ-MC showed good concurrent validity, internal consistency and test-retest reliability. Responsiveness was shown by significant changes in LCQ-MC scores between steady state, the first exacerbation and following 2-week antibiotic treatment (both interval changes, P < 0.01) CONCLUSION: The LCQ-MC is a valid, reliable and responsive instrument for determining cough-specific health status in Chinese bronchiectasis patients.

Use of a two-way non-rebreathing valve to simplify the measurement of twitch mouth pressure using an inspiratory pressure trigger and the establishment of an optimal trigger threshold for healthy subjects and COPD patients.

OBJECTIVE: Controlled twitch mouth pressure (Tw Pmo) via the use of a two-way non-rebreathing valve is a new method to assess diaphragm contractility. The optimal trigger threshold was confirmed. DESIGN: We sought to determine the optimal trigger threshold for 17 healthy subjects (29±4 years) and 17 COPD patients (64±10 years). The Tw Pmo, twitch oesophageal pressure (Tw Pes) and twitch transdiaphragmatic pressure (Tw Pdi) in response to phrenic nerve stimulation were measured using an inspiratory pressure trigger at -1, -2, -3, -4, -5 and -6 cmH2O. RESULTS: The lung volume did not change during triggering at different trigger thresholds using a two-way non-rebreathing valve. The highest correlation between Tw Pmo and Tw Pes in healthy subjects and COPD patients occurred for a -2 cmH2O trigger threshold (r=0.939 and r=0.869, P<0.0001). The narrowest limits of agreement for Tw Pmo and Tw Pes both occurred at -2 cmH2O in healthy subjects, with a bias (range) of -0.4 cmH2O (-1.85 to 1.41), and in COPD patients, with a bias (range) of 0.1 6cmH2O (-1.36-1.67). CONCLUSIONS: We conclude that the measurement of Tw Pmo using a two-way non-rebreathing valve is of clinical value to investigate the suspected diaphragm contractility. The highest trigger threshold for clinical applications was -2 cmH2O.

Recurrent splice-site mutation in MBTPS2 underlying IFAP syndrome with Olmsted syndrome-like features in a Chinese patient.

Mutations in MBTPS2 have been reported to cause a broad phenotypic spectrum of X-linked genodermatoses, including IFAP (ichthyosis follicularis; atrichia and photophobia) syndrome (OMIM 308205) with or without BRESHECK (brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia) syndrome, keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) and an X-linked form of Olmsted syndrome. We report a recurrent intronic mutation in MBTPS2 (c.671-9T>G) in a Chinese patient with the typical triad of IFAP syndrome (i.e. ichthyosis, atrichia and photophobia), along with pachyonychia, palmoplantar and periorificial keratoderma, which were reminiscent of Olmsted syndrome. Interestingly, this mutation was previously reported in two cases of IFAP without keratoderma, which suggests clinical heterogeneicity of the same mutation in MBTPS2. The concomitance of Olmsted syndrome-like features in this patient with IFAP may challenge the existence of the X-linked form of Olmsted syndrome as an independent condition.

A new germline mutation in KIT associated with diffuse cutaneous mastocytosis in a Chinese family.

Diffuse cutaneous mastocytosis (DCM) is an extremely rare disease characterized by massive proliferation of mast cells infiltrating the entire skin. We report a Chinese family with indolent DCM, and detection of a new germline KIT mutation located in the fifth immunoglobulin-like loop of the KIT protein, which probably results in a gain-of-function effect and consequent overactivation of mast cells. Our report expands the knowledge of correlations between the genotype of KIT mutations and the phenotype of DCM.

Unique features of PTCH1 mutation spectrum in Chinese sporadic basal cell carcinoma.

BACKGROUND: Alterations of the PTCH1 gene have been found to contribute to both familial and sporadic basal cell carcinoma (BCC), especially in Caucasian patients. Furthermore, the majority of PTCH1 gene mutations in sporadic BCCs in Caucasian patients carry ultraviolet (UV) signatures, suggesting the key role of UV light in BCC development. However, sporadic BCC in non-Caucasian population has a lower incidence, and the pathogenesis remains largely unknown. To date, there has been no mutation analysis on PTCH1 gene in Chinese patients with sporadic BCCs. OBJECTIVE: To investigate genetic alterations of the PTCH1 gene in Chinese sporadic BCCs. METHODS: Direct sequencing was used to screen for mutations in PTCH1 in 31 microdissected samples in Chinese sporadic BCCs. In addition, single nucleotide polymorphisms (SNPs) were studied for loss of heterozygosity (LOH). RESULTS: Nineteen PTCH1 mutations in 17 of the 31 BCCs (54.8%) were identified. SNP analysis revealed LOH of PTCH1 in 10 of 23 BCCs (43.5%). Interestingly, the majority of mutations identified (63.2%) were insertion/deletion, which was different from the results in Caucasian cases whose mutations are predominantly point mutations. Only two (10.5%) of the remaining seven mutations were UV-specific C → T transition or tandem CC → TT transitions. All mutations occurred evenly throughout the entire PTCH1 protein domain without a hot-spot detected. CONCLUSION: Mutations and LOH in PTCH1 were also highly prevalent in Chinese sporadic BCCs. However, UV light plays a less role in causing these mutations, suggesting other potential mechanisms in the development of sporadic BCC in Chinese patients.

p38a MAPK is involved in BMP-2-induced odontoblastic differentiation of human dental pulp cells.

AIM: To investigate whether the p38α mitogen-activated protein kinases (MAPK) is involved in bone morphogenetic protein (BMP)-2-induced odontoblastic differentiation of human dental pulp cells (HDPCs). METHODOLOGY: Recombinant retrovirus encoding shRNA against p38α MAPK was constructed to investigate the role of p38α MAPK on BMP-2-induced odontoblastic differentiation of HDPCs. HDPCs were transfected with retrovirus expressing sh-p38α. Activation of p38α MAPK was detected by Western blot. The effects of p38α MAPK on BMP-2-induced odontoblastic differentiation of HDPCs were measured by alkaline phosphatase (ALP) activity, and the expression of odontoblastic markers was identified by quantitative real-time polymerase chain reaction analysis. The effect of SD-282, a p38a-specific inhibitor, on BMP-2-induced odontoblastic differentiation was also investigated. RESULTS: BMP-2 dose- and time-dependently upregulated phosphorylation of p38α of HDPCs. Compared with BMP-2-treatment group, gene knock-down of p38α MAPK significantly inhibited ALP activity and the formation of mineralized nodules in HDPCs. Moreover, suppression of p38α MAPK repressed the odontoblastic differentiation in HDPCs. Consistently, inhibition of p38α by SD-282 also decreased odontoblastic differentiation. CONCLUSIONS: p38α MAPK is involved in BMP-2-induced odontoblastic differentiation of HDPCs.

Association of IL-1 gene complex members with ankylosing spondylitis in Chinese Han population.

There are reports of IL-1 complex gene polymorphisms in ankylosing spondylitis (AS; MIM 106300), but the results have been inconsistent among populations. Moreover, few studies examine the association between IL-1 complex gene polymorphisms and clinical symptoms of AS patients. We investigated polymorphisms of IL-1 complex with AS in the Chinese Han population in this study. Chinese Han AS patients and ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (IL1beta+3953, beta-511, F10.3, RN.4, RN.6/1) and the IL1RN.VNTR of IL-1 gene cluster. Allele, Genotype and haplotype frequencies were compared between cases and controls by SHEsis software. The frequency of allele C of the marker IL1F10.3 was significantly increased in AS patients versus controls [p = 0.001, odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.19-1.20; p = 0.002, respectively]. Strong linkage disequilibrium was identified between IL1B-511, IL1B+3953 and RN4 in both patients and healthy controls (D' > 0.95). Haplotypes of pairs of these markers (6) were also significantly associated with AS. The strongest associations observed was between allele combination B-511-T/B+3953-C/F10.3-C/RN4-T/RN2VNTR-1/RN6.1-C and AS (p = 3.32 x 10(-5), OR = 4.41, 95% CI=2.1-9.3). Clinical manifestation showed week association between RN2VNTR A2 allele and risk of peripheral arthritis (OR = 0.2, 95% CI = 0.07-0.91). The IL-1 gene cluster is associated with AS in Chinese population. This finding provides strong statistical support for the previously observed relationship and indicates possible association between clinical manifestation and genetic factor.