Abstract: Objective To investigate the type and distribution of drug resistance of Mycobacterium tuberculosis (MTB) in Hainan tuberculosis hospital from 2019 to 2021, and to provide reference for the development of drug resistant tuberculosis prevention and control strategy. Methods From 2019 to 2021, a total of 1 687 strains of sputum were isolated and cultured and identified as MTB. Drug sensitivity testing was performed on eight anti-tuberculosis drugs: isoniazid (INH), rifampicin (RFP, R), ethambutol (EMB), streptomycin (SM), kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), and propylthioisoniacamide (PTO). The drug resistance analysis was conducted. Results Among the 1 687 MTB strains, the overall drug resistance rate was 41.32% (697), with a single drug resistance rate of 11.62% (196), a multi-drug resistance rate of 4.10% (69), a extensive drug resistance rate of 23.71% (400), a pan-drug resistance rate of 1.90% (32), and a rifampicin resistance rate of 28.10% (474), and the main drug resistance types were extensive drug resistance and rifampicin resistance. The order of resistance to the eight drugs was OFX (64) > SM (62) > INH (48) > RFP (19) > CPM (2) > KM (1) > EMB (0) and PTO (0). The rate of resistance to INH and RFP of first-line drugs in newly treated patients was lower than that in retreated patients (χ2=0.110, 0.765; P>0.05); the rate of resistance to second-line drugs OFX, CPM and KM in initially treated patients was lower than that in retreated patients (χ2=1.037, 1.212, 1.653; P>0.05). The total drug resistance rate in 2019 was 51.16%, which was higher than that in 2020 (35.08%) and 2021 (38.89%). The difference between groups was significant (χ2=29.25,16.60; P=0.000), but there was no significant difference in overall drug resistance rate between 2020 and 2021 (χ2=1.823, P=0.177). Among the occupational types of tuberculosis patients, farmers were the main ones, accounting for 56.25% (949). The patients with drug-resistant tuberculosis were mainly distributed in Haikou City (165) > Wanning City (72) > Chengmai County(64) > Wenchang City (51) = Dongfang City (51) > Danzhou City (48), and patients in these six areas accounting for 64.71%(451/697). Conclusions The drug resistance rate of tuberculosis in Hainan Province is relatively high, with OFX and SM resistance being the main types of drug resistance. The extensive drug resistance rate is higher than the national average level. Therefore, surveillance and treatment should be strengthened and optimized to reduce the prevalence of drug-resistant tuberculosis.

Abstract: Objective To investigate the occurrence of multidrug-resistance among tuberculosis patients in Hainan Province from 2014 to 2020 and to analyze the influencing factors, aiming to provide reference for formulating drug-resistant tuberculosis control strategies in this region. Methods This study collected sputum samples from the patients with pulmonary tuberculosis admitted to the Second Affiliated Hospital of Hainan Medical University from 2014 to 2020, and performed isolation and identification of Mycobacterium tuberculosis and drug susceptibility testing. After the strains were identified as positive, drug sensitivity tests were conducted, and multi-drug resistant patients were found. Clinical data was retrospectively collected, and chi-square test and unconditioned logistic regression were used to analyze the influencing factors of multidrug resistance. Results A total of 2 672 patients underwent sputum culture, strain identification, and drug susceptibility testing in TB designated hospitals in Hainan Province from January 1, 2014 to December 31, 2020. Among them, 1 942 patients with available drug susceptibility test results and complete clinical data were enrolled, among which 398 cases with drug-resistant TB were included in the case group, and 1 544 cases without drug resistance were included in the control group. Multivariate logistic regression analysis showed that farmers, rural residence, treatment history of retreatment, irregular medication history, number of pulmonary cavities ≥3, and BMI<18.5 were independent risk factors for MDR-TB. The risk of MDR-TB in farmers was higher than that in non-farmers (OR=1.542, 95%CI: 1.150-2.020); patients living in rural areas had a higher risk of multidrug resistance than those living in urban areas (OR=1.445, 95%CI: 1.095-1.907); the risk of MDR in the retreatment patients was higher than that in the initial treatment patients (OR=5.616, 95%CI: 4.250-7.421); the risk of multi-drug resistance in patients with irregular medication was higher than that in patients with regular medication (OR=2.665, 95%CI: 2.012-3.531); the risk of multidrug resistance in patients with pulmonary cavity number ≥3 was higher than that in patients with pulmonary cavity number <3 (OR=5.040, 95%CI: 3.768-6.740); compared with patients with BMI<18.5, patients with BMI=18.5-24.0 and BMI≥24.0 had a lower risk of multidrug resistance (OR=0.735, 95%CI: 0.555-0.975 and OR=0.447，95%CI:0.225-0.888, respectively). Conclusions Retreatment, farmer occupation, rural residence, irregular medication and low BMI may be the risk factors for multidrug resistance in Hainan Province.

Objective To investigate the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor on lipopolysaccharide (LPS)-induced changes in the mass and function of pancreatic β-cells.Methods RINm cells were cultured and treated with LPS alone or combined with different concentrations of sitagliptin for 24 h.The proliferation of RINm cells was detected by CCK-8 assay.Apoptotic rate was determined by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide flow cytometry.Insulin secretion was measured by enzyme-linked immunosorbent assay.The expression of IL-6 mRNA was displayed by RT-PCR.Results LPS significantly stimulated the proliferation of RINm cells (0.89 ± 0.04 vs 1.14 ± 0.08,P＜0.01),while LPS+sitagliptin showed no significant difference compared with LPS group.The cell apoptotic rate in LPS + 10-1 mmol/L sitagliptin group was significantly lower than that in LPS group.There were no significant differences in basal insulin secretion among all groups,but after the high/low glucose stimulation,LPS increased insulin secretion as compared with the control.The IL-6 mRNA expression in LPS+sitagliptin group was significantly lower than that in LPS group (0.77 ± 0.33 vs 1.30 ± 0.41,P =0.006).Conclusions DPP-4 inhibitor has no influence on LPS-induced proliferation of pancreatic β-cell,but it can inhibit LPS-induced apoptosis and insulin secretion,and IL-6 may be involved in the process.

OBJECTIVETo investigate the application of medpor and split-thickness skin graft in formation of cranioauricular sulcus during auricular reconstruction with Nagata method.

METHODSThe first stage operation was fulfilled according to the Nagata two-stage method which involves fabrication and grafting of the costal cartilage framework. The second-stage ear elevation operation was undertaken 6 months later to form the cranioauricular sulcus. Split-thickness skin was taken from temporal and accipital area. After releasing the auricular framework and transplanting C shaped medpor at the rear side of framework, the temporaparietal fascia flap was transferred to cover postauricular medpor and framework. Then the split-thickness skin graft was implant on the fascia surface.

RESULTSFrom July 2010 to August 2012, 20 cases (22 ears) were treated. Partial necrosis of temporaparietal fascia flap and framework exposure happened in 1 case. Successful ear reconstruction was achieved in other cases with satisfactory cranioauricular sulcus during the follow-up period of 6-18 months (average, 13 months).

CONCLUSIONSThe application of medpor and split-thickness skin graft in the ear elevation of Nagata method for auricular reconstruction for microtia can achieve satisfactory results. It not only avoids the obvious scar in the donor site due to harvesting full-thickness and intermediate-thickness skin, but also reduces chest trauma due to harvesting costal cartilage.

Costal Cartilage ; transplantation ; Dermatologic Surgical Procedures ; methods ; Ear Auricle ; surgery ; Fascia ; Humans ; Polyethylenes ; therapeutic use ; Skin Transplantation ; Surgical Flaps ; transplantation

Objective To investigate the clinical presentation,laboratory features,imaging findings and CYP27A1 gene mutations of cerebrotendinous xanthomatosis (CTX) for improving the recognition and the early diagnosis and treatment of the disease.Methods Medical records and 8 months follow-up data of one patient who had been clinical diagnosed as CTX were collected and the pedigree and gene mutation analysis of the patient were carried out.Meanwhile,the clinical characters of CTX were analyzed according to the data from our patient and the review of the literature. Results Patient was a 36 years old male manifested with mental retardation, bilateral corticospinal tract and corticonuclear tract impairment,cerebellar lesions and peripheral neuropathy; head MRI indicated symmetric abnormal signals of bilateral basal ganglia,cerebellar dentate nucleus softening and calcification lesions; Achilles tendon MRI indicated markedly thickened Achilles tendon; gene mutation analysis showed sterol-27-hydroxylase gene( CPY27A1 )C→T homozygous mutation in 1016 nucleotide of exon 5.Ursodesoxycholic acid was given as treatment.In 8 months of follow up,for the first 6 months,the patient took medicine regularly and the illness condition was stable.But for the nearly 2 months,the patient voluntarily stopped medicine and the illness condition was worse.Conclusions CPY27A1 gene C→T homozygous mutation in 1016 nucleotide of exon 5 leads to CTX in the patient, which conforms to the characteristic of autosomal recessive disorder. CTX has some characteristic clinical manifestations,such as Achilles tendon thickening,intelligent declining and so on.But lack of specificity of early radiographic examination makes CTX easy to be delayed diagnosis and treatment.CYP27A1 gene mutation analysis has an important significance for early diagnosis of CTX,which should be paid more attention,while the early application of chenodeoxycholicacid treatment can delay the progression of the disease.

Objective To investigate the the relationship of a high risk serum screen for Down syndrome in second trimester and adverse pregnancy outcomes,and to evaluate the predictive value for adverse pregnancy outcomes.Methods The tri-marker second trimester maternal serum screening for Down syndrome (alpha-fetoprotein,free beta-hCG and unconjugated estriol)was performed on the pregnant women at Peking Union Medical Hospital from January 2009 to January 2011.The cutoff valvue was 1/270.Pregnancy outcomes were followed up.The general condition and pregnancy complications of the pregnant women with high risk (high-risk group) were compared to that of the pregnant women with low risk (low-risk group); and with 35 years old as a demarcation,the incidences of adverse pregnancy outcomes were calculated in the two groups.Results ( 1 ) A total of 1935 cases were collected.And 1784 cases were with low risk,and 151 cases were with high risk.The difference of weight and gestational age betweem the two groups was not statistically significant ( P ＞ 0.05 ) ; the difference of age between the two groups was statistically significant ( P ＜ 0.01 ).(2) Pregnancy complications were found in 791 cases.In high-risk group,the incidences of gestational diaetes mellitus (GDM,13.9％),neonatal asphyxia (4.0％ ) and small for gestational age infant ( SGA,4.6％ ) were higher than that in low-risk group ( 8.4％,1.0％,1.6％ ),the difference was statistically significant ( P ＜ 0.05 ).The incidences of gestational hypertension disease,premature labor,oligohydrammios,placenta previa,placenta abruption,fetal macrosomia in the two groups was not statistically different (P ＞0.05).(3) In 1705 cases aged less than 35 years,129 cases (7.6％) were GDM,43 cases ( 2.5％ ) were gestational hypertension disease,61 cases ( 3.9％ ) were premature labor; in 230 cases aged 35 years or more,41 cases (17.8％ ) were GDM,12 cases (5.2％) were gestational hypertension disease,15 cases (6.5％ ) were premature labor,and the difference between the two groups was statistically significant ( P ＜ 0.05 ).In ＜ 35 years old group,the incidences of GDM,neonatal asphyxia and SGA (12.3％,4.4％,5.3％ ) were higher in the high-risk group than that (7.2％,0.9％,1.6％ ) in the low-risk group,and the difference was statistically significant ( P ＜ 0,05 ).In ≥35 years old group,the incidences of GDM,neonatal asphyxia and SGA ( 18.9％,2.7％,2.7％ ) were slightly higher in the high-risk group than that (17.6％,1.6％,1.6％ ) in the low-risk group,the difference between the two groups was not statistically significant (P ＞ 0.05 ).Conclusions The present study revealed apparertt increase in the adverse pregnancy outcomes in women with a high risk of Down syndrome screening test.Advanced age is the most important risk factor for a high risk of Down syndrome screening test and adverse pregnancy outcomes.More attention should be attached to the patients whose age were ＜35 years old and with a high risk of Down syndrome screening test.

To compare the effects of four different intensive insulin therapies on blood glucose control and vascular endothelial function in newly-diagnosed type 2 diabetes.Patients were randomly divided to accept pre-meal insulin aspart 30 or pre-meal insulin aspart and glargine at bedtime or pre-meal Novolin-R and NPH at bedtime or continuous subcutaneous insulin aspart infusion.Capillary blood glucose determination and continuous glucose monitoring system were carried out,therapeutic time and total insulin dosage were recorded.Ultrasound was used to evaluate the vascular endothelial function.Glucose level,incidence of low glucose,potency ratio of the four groups were similar( P＞0.05 ) ; FMD and NMD were not significantly improved ( P =0.718,P =0.065 ).The short-term efficacy and safety of the four groups are similar.The short-term intensive insulin therapy has no obvious effect on vascular endothelial function.

ObjectiveTo investigate serum lipopolysaccharide (LPS) level in people with different glucose tolerances and to explore the relationship between LPS and insulin resistance/β-cell secretory function.Methods Sixty-seven subjects were recruited,including 23 with newly diagnosed type 2 diabetes ( T2DM),21 impaired glucose tolerance ( IGT),and 23 normal glucose tolerance (NGT).Serum LPS was assayed by limulus amebocyte lysate test ;expression of LPS toll-like receptor 4 (TLR4) on surface of plasma monocytes was measured by flow cytometric assays,and the changes of LPS levels by 0.5 hours and 2 hours after a high-fat diet were detected.Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR); β-cell secretory function was evaluated by homeostasis model assessment for β3 cell function ( HOMA-β )/HOMA-IR,increment in insulin in the first 30 minutes/increment in glucose in the first 30 minutes ( AIns30/ΔG30)/HOMA-IR,AUCIns120min/HOMA-IR.Results2 h LPS levels after a high-fat diet were significantly higher than fasting LPS levels [ NGT:0.96(0.33,0.99)vs 0.62 (0.22,0.64),IGT:1.08(0.53,1.22)vs 0.71 (0.39,0.82),T2DM:1.23 (0.62,1.43)vs 0.86( 0.45,0.94 ),EU/ml,all P＜0.01 ].Fasting,0.5 h,and 2 h LPS levels and fasting TLR4 levels of T2 DM group and IGT group were respectively higher than those of NGT group [ fasting LPS:0.86( 0.45,0.94 ),0.71 ( 0.39,0.82 ) vs 0.62(0.22,0.64),EU/ml;0.5 h LPS:1.10(0.55,1.18),0.84(0.50,1.07) vs 0.73(0.31,0.76),EU/ml;2 h LPS:1.23(0.62,1.43),1.08(0.53,1.22)vs 0.96(0.33,0.99),EU/ml; fasting TLR4:36.96( 17.22,55.19),30.34 ( 15.00,45.18 )vs 15.66 (6.09,9.76),MIF/105 cells,all P＜0.01 ].Fasting LPS,AUCLPS 120 min,and fasting TLR4 were positively correlated with insulin resistance index and negatively correlated with β-cell secretory function index ( P＜0.05 ).Multiple linear regression analysis showed that fasting LPS was an independent correlative factor of HOMA-IR and 0.5 h LPS was an independent correlative factor of (AIns30/AG30)/HOMA-IR and AUCIns Ins120min/HOMA-IR.ConclusionPeople with different glucose tolerances show differed LPS levels and its receptor TLR4 levcls,both of which are correlated with insulin resistance and β-cell secretory function,suggesting that LPS is associated with the pathogenesis of abnormal glucose regulation.

Objective To analyze the relationship between karyotypes and clinic features of patients with primary amenorrhea. Method Karyotype analysis of patients with primary amenorrhea was performed by using G-banding technique. Results Karyotype analysis of 468 patients with primary amenorrhea revealed that 255 patients (54. 49% ) had normal female karyotypes and 213 patients (45.51%) had abnormal karyotypes, including 143 patients with abnormal X chromosome, 4 patients with mosaic X -Y chromosome, 57 patients with 46, XY karyotype, 8 patients with abnormal autosome and one patient with Xautosome translocation. 75.52% primary amenorrhea patients with short stature had abnormal X chromosome, and all primary amenorrhea patients with deletion or break-up of Xp11. 1 - 11.4 and Xp21 - 22 were short statures. Conclusion One of the main reasons of primary amenorrhea was chromosome abnormity,especial heterosome abnormity. Karyotype analysis should be used to detect primary amenorrhea patients in regular. There might be relationship between height improvement and the abnormity of Xp11. 1 - 11.4 and Xp21 - 22.

ObjectiveTo investigate the effects of lipopolysaccharide ( LPS ) on cell apoptosis,proliferation, and insulin secretion in a β-cell line, NIT-1. MethodsNIT-1 cells were stimulated with 1 μg/ml LPS for 0-120 h. Cell apoptosis was evaluated by Hochest33342 staining and Annexin V/PI flow cytometry. Cell proliferation was evaluated by CCK-8 and BrdU assay. Intracellular insulin content, basal insulin secretion, and glucose-stimulated insulin secretion(GSIS) were detected by RIA. The IRS-2 tyrosine phosphorylation was determined by Western blot. ResultsCell apoptosis was not significantly changed by treatment with LPS for 120 h. Cell proliferation was stimulated by LPS before 48 h, and inhibited after 96 h. Intracellular insulin content or GSIS was not altered, but basal insulin secretion was decreased significantly by LPS after 48 h ( all P＜0.01 ). LPS decreased the tyrosine phosphorylation level of IRS-2 ( 0. 45 ± 0. 08 vs 0. 22 ± 0. 06, P ＜ 0. 05 ) and stimulated IκBα phosphorylation. Pretreatment with a specific IκBα phosphorylation inhibitor, Bay1 1-7082 for 1 h, remarkably blunted the LPS-induced phosphorylation of IκBα and cell proliferation( both P＜0.01 ). ConclusionsLow-dosages of LPS regulate proliferation and basal insulin secretion of NIT-1 β-cells, in which activation of NF-κB and inhibition of IRS2 tyrosine-phosphorylation may be involved.