Objective:To analyze the treatment effect and drug resistance mutation of HIV-1 infected patients who changed to the second-line antiretroviral treatment regimen after they had developed drug-resistance with first-line antiretroviral treatment regimen in some areas of Sichuan Province.Methods:Using the cohort study method, the patients who had developed drug resistance with the first-line regimen were followed up for two years from 1 January 2019 to 31 December 2021.The changes of CD4 +T lymphocytes (CD4) counts and viral load (VL) at the endline and the detection of drug-resistant mutation sites were analyzed using the chi-square test. Multivariate logistic regression model was used to analyze the influencing factors of antiretroviral treatment effect in patients who had good compliance after switching to the second-line regimen. Results:A total of 737 patients were recruited. Among the cases with continuous good compliance, those who timely changed to the second-line regimen had higher proportion of maintaining continuous CD4 >200 cells/μl and sustained virus inhibition ( P<0.05). Among the patients with different levels of drug resistance at baseline, there was no significant difference in continuous CD4 >200 cells/μl and sustained VL <200 copies/ml ( P>0.05). After changing to the second-line regimen, the drug-resistant mutation sites of some protease inhibitors showed an upward trend, while those of the non-nucleoside reverse transcriptase inhibitors showed a downward trend ( P<0.05). Multivariate logistic regression analysis showed that, among patients who had good compliance and who had switched to the second-line regimen, mother-to-child-transmitted patients had 3.01 times higher risk than heterosexual sexually transmitted infection (95% CI:1.29-7.00), failure to change the second-line protocol in time brought 2.55 times higher risk than that of timely changing to the second-line regimen (95% CI:1.41-4.62) and patients who infected with CRF85_BC subtype had 3.32 times higher risk than those infected with CRF01_AE subtype (95% CI:1.49-7.42). Conclusions:Difference in the drug resistance levels with the first-line regimen does not affect patients' antiretroviral treatment effect after changing to the second-line regimen in Sichuan Province. Changing to the second-line regimen in time and maintaining good compliance are beneficial to higher immune levels and lower VLs in drug-resistant patients. Among patients who changed to the second-line regimen, mother-to-child transmission, failure to change the second-line program in time, and infection with CRF85_BC virus are risk factors endangering antiretroviral treatment success after changing to the second-line regimen.

【Objective】 To investigate the clinicopathological characteristics and prognosis of solitary fibrous tumor (SFT) in the retroperitoneum. 【Methods】 We summarized the clinical and prognostic data of nine patients admitted to The First Affiliated Hospital of Xi’an Jiaotong University between January 2007 and December 2017 who were diagnosed with SFT by surgical resection and pathological examination. Nine cases of retroperitoneal SFT were detected by HE and immunohistochemical SP method. The expressions of Vimintin (Vim), CD34, CD99, Ki-67, Bcl-2 and S-100 in tumor cells were analyzed for their clinicopathological characteristics and prognosis. 【Results】 Among the nine patients, four were male and five were female, aged 37-69 years old. Five of them showed abdominal distension, while the other four had no obvious clinical symptoms. The tumor size was (1.0 cm×1.0 cm×2.0 cm)-(30.0 cm×25.0 cm×10.0 cm). There were seven single cases and two multiple cases. Histology showed bundle-shaped, braided spindle cells and collagen fibers of varying degrees, accompanied by mucinous degeneration and hemangiopericytoma-like morphology. Immunohistochemical results were as follows: The positive rate was 100% (9/9) for Vim, CD34 and CD99, 77% (7/9) for Ki-67, 67% (6/9) for Bcl-2, and 22% (2/9) for S-100. All the patients were followed up effectively. Two of them died (the cause of death was not related to the disease studied, and the survival time from postoperative to death was 6.5 years and 8.3 years, respectively). One surviving case relapsed 3 years after the operation, but did not recur after the second operation. No recurrence or metastasis was found in the remaining cases. 【Conclusion】 Retroperitoneal SFT is rare in the clinic, and there are no typical clinical symptoms in the early stage. Most of them are detected in physical check-ups. Ultrasound and CT examinations are the main preoperative examination methods, but they are not specific to SFT. Pathological examination is the only method for diagnosis. Radical resection is the first-choice of treatment. The preferred method for this disease is effective in early radical surgery and regular postoperative review.

Objective:To understand influencing factors on the deaths of HIV/AIDS patients receiving antireviral treatment in Butuo county of Liangshan Yi Autonomous Prefecture (Liangshan) from 2010 to 2019, to provide data for drug replacement and sustainable antiviral treatment strategy.Methods:A matched case-control study was used to collect basic and follow-up information on AIDS death patients receiving antiviral treatment in Butuo county of Liangshan from 2010 to 2019. The control group was formed by sampling twice the number of cases. The logistic regression model was used to analyze the risk factors affecting mortality.Results:In 3 355 patients of HIV/AIDS treated with antiviral therapy, 1 179 cases in the death group and 2 176 cases in the control group. Including 81.34% were 30-49 years old, 69.09％males, 99.55% Yi nationality, 91.12% were married or cohabitated, 95.77% had junior high school education or below, and 88.41% peasants. Amultivariate logistic stepwise regression model showed that among the death risk factors, age ≥50 years old was 5.08 times (95% CI:3.05-8.48) that of the 18-29, female was 0.70 times (95% CI: 0.52-0.94) than male, the transmission rate of intravenous drug use was 1.43 times (95% CI: 1.06-1.91) that of heterosexual transmission, CD4 +T lymphocyte (CD4) count ≥350 cells/μl before treatment was 0.38 times (95% CI: 0.30-0.48) that of CD4 <200 cells/μl before treatment, the most recent antiviral treatment regimen containing LPV/r was 0.04 times (95% CI: 0.01-0.18) than that of stavudine (d4T) + lamivudine (3TC) + nevirapine (NVP)/efavirenz (EFV) regimen, drug resistance was 3.40 times (95% CI: 2.13-5.42) of non-drug resistance, non-viral load and non-drug resistance test results were 12.98 times (95% CI: 10.28-16.40) of non-drug resistance. Conclusions:Age, gender, transmission route, CD4 before treatment, the latest antiviral treatment program, and drug resistance test after antiviral therapy were the influencing factors of HIV/AIDS death in Butuo county. It is necessary to expand the coverage of viral load and drug resistance test to change the antiviral therapeutic schedule scientifically and carry out publicity and education on the compliance of patients with antiviral treatment and medical staff training in order to reduce the mortality of patients with antiviral treatment.

Objective To investigate the roles of CD3+,CD4+,CD8+T lymphocytes and CD19+B lymphocytes on the pathogenesis of acute respiratory distress syndrome(ARDS).Methods According to Berlin definition Of ARDS in 2012,34 patients with ARDS admitted in the Department of ICU of Central Hospital of Baoji from January,2016 to January,2017 were enrolled in this study as study group(ARDS group).At the same time,22 healthy subjects were recruited as control group.Clinical data of ARDS patients were collected,and the survivors were followed up.The ARDS patients were divided into moderate group(n=20) and severe group (n=14) according to clinical settings on the first day after diagnosis of ARDS and Berlin Definition of ARDS in 2012,and at the same time they were also dividedinto two groups according to the outcome followed up for 28 days:non-survival group(n=14) and survival group(n =20).Sample of 3 mL peripheral venous blood of ARDS patients was collected on an empty stomach in the early morning on the first day after diagnosis of ARDS and the blood samples of healthy subjects were also collected on the first day to measure the level of CD3+,CD4+,CD8+T cells and CD19+ B cell in peripheral venous blood by flow cytometry.Comparison of CD3+,CD4+,CD8+ T cells and CD 19+ B cell numbers were carried out between ARDS group and control group on the first day after diagnosis of ARDS,and between moderate group and severe group as well as between survival group and nonsurvival group.The risk factors associated with ARDS were analyzed using logistic regression analysis.Results On the first day after diagnosis of ARDS,there were significant differences in serum Lac and pre-albumin between survival group and non-survival group(P＜0.05).The numbers of CD3+,CD4+T cells and CD19+B cell of peripheral venous serum in ARDS group were significantly lower than those in control group(P＜0.05),while there was no significant difference in CD8+ T cell number between ARDS group and control group (P＞0.05).There were statistically significant differences in numbers of CD3+,CD4+,CD8+T cells and CD19+B cell between moderate group and severe group and as well as between survival group and non-survival group(P＜0.05).Logistic regression analysis showed that CD19+B cell (OR=0.614,95％CI:0.416-0.907,P=0.014) level on the first day after diagnosis of ARDS was related with the risk of prognosis of ARDS.The ROC of CD19+B cell had area under curve(AUC) of 0.907,and the cut-off value of CD19+B cell in the survival followed up for 28 day's was 12.59％.Conclusions CD3+,CD4+,CD8+T cells and CD19+B cell level of peripheral venous serum in ARDS patients can be helpful for the assess of ARDS severity of patients in the early stage,and for prognosis judgment,especially CD 19+B cell is more remarkable.

Objective: To expand the knowledge of the clinical and molecular characteristics of the children with Bloom syndrome. Methods: Clinical data of two siblings with classic Bloom syndrome of Shanghai Children's Medical Center from January 2009 to June 2017 were obtained and analyzed. The DNA of peripheral blood was collected from two Bloom syndrome siblings and their parents during 2015. The mutations were detected with high-throughput sequencing by Illumina sequencing platform. Results: The two siblings (probands) visited our department for short stature and growth retardation, they had full-term normal delivery after normal pregnancy of their mother. Both cases presented with feeding difficulties, malnutrition, microcephaly and mental retardation, repeated infection, symmetrical short stature and special faces. At first, the proband was an 8-year-3-month old girl, her height was 99.7 cm, body mass index (BMI) 12.07 kg/m², head circumference was 45.5 cm, and birth weight was 1.6 kg. Her younger brother was 3-year-11-month old, his height was 86.6 cm, BMI was 14 kg/m², birth weight was 1.95 kg, and the head circumference reached 36 cm at 16 months. No evidence of cancer and characteristic rash was detected at 8-year follow-up. Pathogenic complex heterozygous mutations c.772_773delCT, p.Leu258Glufs*7 and c.959+ 2T>A in BLM gene were detected in both siblings, which were separately inherited from their unaffected parents. Besides , c.959 + 2T>A has not been reported previously. Conclusions Children with Bloom syndrome are characterized by short stature, microcephaly, special faces, feeding difficulties, and immunodeficiency. And butterfly erythematous rash may be absent. The c.959+2T>A mutation detected in our patients maybe a novel pathogenic mutation.

OBJECTIVETo identify the genetic cause for a 11-year-old Chinese boy with Meier-Gorlin syndrome (MGS).

METHODSChromosomal microarray analysis (CMA) was used to detect potential variations, while whole exome sequencing (WES) was used to identify sequence variants. Sanger sequencing was used to confirm the suspected variants.

RESULTSThe boy has featured short stature, microtia, small patella, slender body build, craniofacial anomalies, and small testes with normal gonadotropin. A complete uniparental disomy of chromosome 16 was revealed by CMA. WES has identified a novel homozygous mutation c.67A>G (p.Lys23Glu) in ORC6 gene mapped to chromosome 16. As predicted by Alamut functional software, the mutation may affect the function of structural domain of the ORC6 protein.

CONCLUSIONThe patient is probably the first diagnosed MGS case in China, who carried a novel homozygous mutation of the ORC6 gene and uniparental disomy of chromosome 16. The effect of this novel mutation on the growth and development needs to be further investigated.

Base Sequence ; Child ; Chromosomes, Human, Pair 16 ; genetics ; Congenital Microtia ; genetics ; Family Health ; Fathers ; Growth Disorders ; genetics ; Heterozygote ; Humans ; Male ; Micrognathism ; genetics ; Mutation ; Origin Recognition Complex ; genetics ; Patella ; abnormalities ; Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA ; methods ; Uniparental Disomy ; genetics

Objective To explore the clinical manifestation and gene mutation of primary renal glucosuria (PRG). Methods The clinical data and gene detection results of a child with PRG were analyzed. Results A girl aged 2 years and 10 mouths had glucose ++++ by urine dipstick analysis and 22.4 g of the 24 h urine glucose. Her father was urine glucose positive. Genome DNA was extracted from peripheral blood of the girl and her parents, SLC5A2 gene were amplified by PCR for sequencing, including exons and splicing areas. The results showed a homozygous point mutation (c.127-16C>A) in girl, and both of her patents had the same heterozygous mutation. This mutation had been classified to pathogenic mutations by ClinVar data base. Conclusions The diagnosis of PRG is confirmed in this child and SLC5A2 gene mutation is the cause.

[Summary] Microcephalic or Majewski's osteodysplastic primordial dwarfism type Ⅱ ( MOPD Ⅱ) is an extremely rare genetic disease mainly caused by pericentrin ( PCNT) gene mutations. This paper reported one 13-year-old boy, who was admitted because of the slow growth for more than 13 years and deepened skin color over six months. He was diagnosed as MOPD Ⅱ associated with a combination of growth hormone deficiency, type 2 diabetes, hypertension, acanthosis nigricans, multiple café-au-lait spots. On magnetic resonance imaging of brain, no vascular malformations such as aneurysms were shown. There were novel compound heterozygous mutations of PCNT gene in the patient, with the nonsense mutations of c. 502C > T ( p. Gln168 * heterozygous variation) and c. 3103C > T (p. Arg1035* heterozygous variation). His father carried a nonsense mutation c. 3103C > T ( p. Arg1035 *heterozygous variation ) and his mother had a nonsense mutation c. 502C > T ( p. Gln168 * heterozygous variation). After treatment with metformin for three months, his blood glucose returned to normal, and acanthosis nigricans was improved. It seems critical to evaluate the abnormal condition of blood vessels regularly for MOPD Ⅱpatients with PCNT gene mutations.

Objective To analyze the clinical feature, diagnosis and treatment of Alstrom syndrome. Method The clinical data of a case of Alstrom syndrome and the result of her ALMS1 sequencing by the two generation sequencing were retrospectively reviewed. Results The 12 year and 10 month old female suffered from dilated cardiomyopathy, obesity, optic nerve diseases, sensorineural hearing loss, high blood glucose and irregular menstruation since one month of birth. Laboratory examination showed she had high testosterone level, hyperglycemia, hyperlipidemia and fatty liver. High-throughput sequencing confirmed there was ALMS1 gene mutation which includes hybrid frameshift mutations of c.5418delC and p.Y1807Tfs*23, and heterozygous nonsense mutation of c.10549C>T and p.Q3517*, and c.5418delC was a new variation reported for the first time. Conclusion Alstrom syndrome is an autosomal recessive genetic disease, which is characterized by multiple organ dysfunction and metabolic syndrome, and can be diagnosed by gene detection.

Objective To analysis the clinical and gene mutation characteristics of hereditary fructose intolerance (HFI). Methods The clinical features and the results of gene testing in the child with HFI and her parents were analyzed retrospectively. Gene sequencing was carried out by high-throughput sequencing and validated by Sanger sequencing. Results The 4-year-3-month old girl had recurrent hypoglycemia episodes and growth retardation. When the condition was stable, the levels of lactic acid and urine micro protein were slightly higher, and the levels of thyroid hormone, cortisol, glycosylated hemoglobin, insulin and C peptide were normal.EEG showed epileptiform activity.Gene sequencing revealed the presence of aldolase B gene(ALDOB) compound heterozygous mutations, a novel splicing mutations (c.325-1G>A) in intron 3 and a frameshift mutation (c. 865delC;p.L289fs*10) in exon 8. Her father carries a frameshift mutation, and her mother carries a splicing mutation. Conclusion The diagnosis of HFI caused by ALDOB mutation can be confirmed by high-throughput sequencing technology.