Hearing loss and its relationship with blood pressure among workers exposed to noise in a brewery / 公共卫生与预防医学

Objective To investigate the health status of workers exposed to noise in a brewery in Beijing and to analyze the relationship between hearing loss and blood pressure. Methods A total of 949 noise-exposed workers in a brewery who participated in occupational health examination were selected as the investigation subjects. A survey was conducted to investigate the pure tone hearing threshold and abnormal blood pressure of the workers with different characteristics, and to analyze the relationship between the two. Results Among the noise-exposed workers, the detection rates of hearing abnormality, hypertension, and increased systolic and diastolic blood pressure were 73.55%, 52.37%, 43.84% and 46.47%, respectively. The detection rates of hearing abnormality, indicators of hypertension, high frequency hearing threshold abnormality and increased binaural high frequency hearing threshold on average in males were higher than those in females (P 0.05), the detection rates of other hearing abnormality, indicators of hypertension, speech frequency hearing threshold abnormality, high frequency hearing threshold abnormality，increased binaural high frequency hearing threshold on average and the weighted value of the better ear's hearing threshold all increased or had an increasing trend with the increase of age or working years (P< 0.05). The detection rates of hypertension in the groups with high frequency hearing threshold abnormality and increased binaural high frequency hearing threshold on average were higher than those in the normal group (P＜0.05). Conclusion The noise-exposed workers in the brewery have hearing impairment, which is related to the occurrence of hypertension. It is recommended to strengthen the publicity and education on noise protection and take protective measures to reduce the occurrence of occupational noise injury.

Pathological Types,Expression of Mismatch Repair Protein,Human Epidermal Growth Factor Receptor 2,and Pan-TRK,and Eostein-Barr Virus Infection in Patients With Colorectal Cancer Resected in Tibet / 中国医学科学院学报

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.

Research progress in diseases associated with genetic variants of GATOR1 complex / 中华医学遗传学杂志

The GATOR1 complex is located at the upstream of the mTOR signal pathway and can regulate the function of mTORC1. Genetic variants of the GATOR1 complex are closely associated with epilepsy, developmental delay, cerebral cortical malformation and tumor. This article has reviewed the research progress in diseases associated with genetic variants of the GATOR1 complex, with the aim to provide a reference for the diagnosis and treatment of such patients.

Genetic analysis of a child with Charlevoix-Saguenay spastic ataxia due to variant of SACS gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS).@*METHODS@#Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases.@*CONCLUSION@#The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.

Analysis of clinical features and PAK1 gene variant in a child with epilepsy and global developmental delay / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical phenotype and genetic basis of a child with epilepsy and global developmental delay.@*METHODS@#A child with epilepsy and global developmental delay who had visited West China Second University Hospital, Sichuan University on April 1, 2021 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. A literature review was also carried out by searching databases such as Wanfang data knowledge service platform, China National Knowledge Infrastructure, PubMed, ClinVar and Embase to summarize the clinical phenotypes and genotypes of the affected children.@*RESULTS@#The child was a 2-year-and-2-month-old male with epilepsy, global developmental delay and macrocephaly. Results of WES showed that the child has harbored a c.1427T>C variant of the PAK1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Only one similar case had been recorded by the dbSNP, OMIM, HGMD, and ClinVar databases. No frequency for this variant among Asian population was available in the ExAC, 1000 Genomes, and gnomAD databases. Prediction with IFT, PolyPhen-2, LRT, Mutation Taster, and FATHMM online software suggested that this variant is deleterious to the function of encoded protein. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the PAK1 gene c.1427T>C variant was determined to be likely pathogenic.@*CONCLUSION@#The PAK1 gene c.1427T>C variant probably underlay the epilepsy and global developmental delay in this child, which has provided a reference for the clinical diagnosis and genetic counseling in children with similar disorders.

Effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor level and morning stiffness time in patients with refractory rheumatoid arthritis / 中国医师杂志

Objective:To investigate the effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor (RF) level and morning stiffness time in patients with refractory rheumatoid arthritis (RA).Methods:A total of 120 patients with refractory RA diagnosed and treated in the First Affiliated Hospital of Hebei North University from June 2019 to June 2020 were selected as the study subjects, and they were randomly divided into three groups by random number table method: etanercept group, etanercept+ methotrexate group, and tofacitinib+ methotrexate group, with 40 patients in each group. The etanercept group was given etanercept treatment, the etanercept+ methotrexate group was given etanercept combined with methotrexate treatment, and the tofacitinib+ methotrexate group was given tofacitinib combined with methotrexate treatment. The clinical efficacy (12 W, 24 W and 48 W of treatment), disease activity, RF level, morning stiffness time and incidence of adverse reactions were compared among the three groups.Results:Comparison of the total clinical effective rate of the three groups: the total clinical effective rate of the etanercept+ methotrexate group and the tofacitinib+ methotrexate group was higher than that of the etanercept group (both P<0.05), and the tofacitinib+ methotrexate group was higher than that of the etanercept+ methotrexate group ( P<0.05). After treatment, the clinical symptoms and disease activity scores (DAS28) in the etanercept+ methotrexate and tofacitinib+ methotrexate groups were significantly improved compared with the etanercept group (all P<0.05), and the improvements in the tofacitinib+ methotrexate group were more significant than those in the etanercept+ methotrexate group ( P<0.05). After treatment, the erythrocyte sedimentation rate (ESR), RF and C-reactive protein (CRP) levels were lower in the etanercept+ methotrexate and tofacitinib+ methotrexate groups than those in the etanercept groups (all P<0.05), and the ESR, RF and CRP levels in the tofacitinib+ methotrexate groups were lower than those in the etanercept+ methotrexate group (all P<0.05). There was no significant difference in the incidence of total adverse reactions among 3 groups (7.50% vs 12.50% vs 12.50%) ( P>0.05). Conclusions:Tofacitinib combined with methotrexate can effectively improve the disease activity, RF level and morning stiffness time in patients with refractory RA, with high safety, which is worthy of clinical application and promotion.

Prevalence of occupational musculoskeletal disorders among workers inheavy-duty automobile parts factories in Beijing Municipality / 预防医学

Objective@#To investigate the prevalence and risk factors of occupational musculoskeletal disorders among workers in heavy-duty automobile parts factories in Beijing Municipality, so as to provide insights into development of effective interventions for occupational musculoskeletal disorders.@*Methods@#The workers in three heavy-duty automobile truck parts factories in Beijing Municipality were recruited using the convenient sampling method during the period from May 2019 to October 2020. Subjects' demographic characteristics, type of job and prevalence of occupational musculoskeletal disorders at various sites were collected using self-designed electronic questionnaires, and the factors affecting the development of occupational musculoskeletal disorders were identified using a multivariable logistic regression model.@*Results@#A total of 264 workers were enrolled, including 260 males (98.48%) and 4 females (1.52%). The participants had a mean age of (31.71±6.13) years, and mean duration of (7.51±5.25) years at current position, and mechanical technician was the major type of work (129 workers, 48.86%). The prevalence of occupational musculoskeletal disorders was 70.08% among the participants, and high prevalence of occupational musculoskeletal disorders was found in the lower back/waist (41.28%), shoulder (40.15%), neck (39.02%) and upper back (33.33%). Multivariable logistic regression analysis identified females (OR=1.280, 95%CI: 1.021-1.602) and head-down posture at work (OR=2.644, 95%CI: 1.034-6.763) as risk factors for occupational musculoskeletal disorders at neck; females (OR=1.633, 95%CI: 1.624-2.117), sheet metal workers, mechanical technicians and painters (OR: 5.811-10.452, 95%CI: 1.205-54.027), working in an uncomfortable posture (OR：1.376-7.749, 95%CI: 1.034-27.270) and frequent working overtime (OR=2.081, 95%CI: 1.192-4.137) as risk factors for occupational musculoskeletal disorders at shoulder; and sheet metal workers, mechanical technicians and painters (OR: 8.760-11.948, 95%CI: 1.630-66.927), working in an uncomfortable posture (OR：4.067-12.185, 95%CI: 1.332-47.523) and frequent working overtime (OR=2.201, 95%CI: 1.142-4.244) as risk factors for occupational musculoskeletal disorders at waist/back.@*Conclusions@#The prevalence of occupational musculoskeletal disorders is high among workers in heavy-duty automobile parts factories, which mainly occur at shoulder, neck, waist and back. Type of work, working posture and working duration are main factors affecting the development of occupational musculoskeletal disorders.

De novo variant of CSNK2B causes Poirier-Bienvenu neurodevelopmental syndrome: two case report / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and CSNK2B gene variant of 2 children with Poirier-Bienvenu neurodevelopmental syndrome, and to identify the possible pathogenic causes and provide evidence for clinical diagnosis.@*METHODS@#Two children with Poirier-Bienvenu neurodevelopmental syndrome were selected from West China Second University Hospital, Sichuan University. The clinical manifestations, laboratory examination and CSNK2B gene variant were analyzed.@*RESULTS@#The main manifestations of 2 children were epilepsy, motor or intellectual retardation. Whole exon sequencing showed that CSNK2B gene c. 291+4A>T heterozygous splicing variant was found in case one, and CSNK2B copy number variation(CNV) was lost in case two. Case one received no special treatment, followed up for 8+ months, seizures and motor development were improved; case two had recurrent seizures for 9+ years, and received levetiracetam and clonazepam antiepileptic treatment. No seizures have occurred for 2 years now, and a large number of epileptic discharges can still be seen in video electroencephalogram (VEEG) with slightly backward intelligence and language development.@*CONCLUSION@#Our study further proves that the pathogenic variant of CSNK2B is related to epilepsy with developmental disorder, and enrich is the CSNK2B gene variant spectrum. The pathogenesis of CSNK2B has great clinical heterogeneity, with great difference in severity of nervous system injury and different prognosis, and agenesis of corpus callosum may be one of its clinical phenotypes.

Analysis of a case with Xia-Gibbs syndrome due to variant of AHDC1 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic characteristics of a child featuring Xia-Gibbs syndrome.@*METHODS@#Whole exome sequencing was carried out for the child.@*RESULTS@#The patient has presented with developmental delay, hypotonia, strabismus and snoring. Cranial MRI revealed hypomyelination, while the EEGs were normal. Genetic testing revealed a de novo variant of the AHDC1 gene, namely c.730delA (p.Ile244Serfs*16), which was classified as pathogenic (PVS1+PS2+PM2). Together with 60 cases from the literature, individuals harboring a AHDC1 variant commonly have delayed motor milestones, speech delay, facial dysmorphism and hypotonia. Dysgenesis of corpus callosum is also common. In total 47 AHDC1 variants have been reported, among which truncating variants were the most common type.@*CONCLUSION@#The c.730delA (p.Ile244Serfs*16) variant of the AHDC1 gene probably underlay the Xia-Gibbs syndrome in this patient. Above finding has provided a basis for the clinical diagnosis.

Analysis of clinical features and ZBTB18 gene variant in a child with autosomal dominant mental disorder type 22 / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and ZBTB18 gene variant in a child with epilepsy and global developmental delay.@*METHODS@#Clinical data and laboratory examination of the patient were reviewed. Whole exome sequencing (WES) was also carried out for the family trio.@*RESULTS@#The main manifestations of the child included global developmental delay, short stature, epileptic seizures. EEG revealed frequent occurrence of sharp (slow) waves in the right central region during sleeping, with sharp waves occasionally seen in the frontal and right posterior temporal regions. Cranial MRI has shown no obvious abnormality. WES has identified a de novo pathogenic variant in the ZBTB18 gene [NM_205768.3: exon 2: c.1282_1283del (p.Phe428Leufs*72)]. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PVS1_Moderate+PM2_Supporting). Following treatment with levetiracetam and rehabilitation, the seizures have been controlled for nearly half a year, with improvement of the psychomotor and language development. So far 28 children have been discovered with ZBTB18 gene mutations, and there was a significant difference in the clinical phenotypes of motor retardation, language retardation and epilepsy between those harboring frameshift/nonsense mutations and missense mutations.@*CONCLUSION@#The c.1282_1283del (p.Phe428leufs *72) variant of the ZBTB18 probably underlay the autosomal dominant mental disorder type 22 in this child. Compared with missense mutations, frameshift/nonsense mutations may predispose more to motor retardation, delayed language development and epilepsy.

Retrospective Analysis of Pathological Diagnosis of Central Nervous System Diseases in Tibet / 中国医学科学院学报

Objective To analyze the disease spectrum and clinicopathological characteristics of central nervous system(CNS)diseases diagnosed based on pathological findings in Tibet. Methods We collected the data of all the cases with CNS lesions in Tibet Autonomous Region People's Hospital from January 2013 to December 2020.The clinicopathological features were analyzed via light microscopy,immunohistochemical staining,and special staining. Results A total of 383 CNS cases confirmed by pathological diagnosis were enrolled in this study,with a male-to-female ratio of 188∶195 and an average age of(40.03±17.39)years(0-74 years).Among them,127(33.2%)cases had non-neoplastic diseases,with a male-to-female ratio of 82∶45 and an average age of(31.99±19.29)years;256(66.8%)cases had neoplastic diseases,with a male-to-female ratio of 106∶150 and an average age of(44.01±14.87)years.The main non-neoplastic diseases were nervous system infectious diseases,cerebral vascular diseases,meningocele,cerebral cyst,and brain trauma.Among the infectious diseases,brain abscess,granulomatous inflammation,cysticercosis,and hydatidosis were common.The main neoplastic diseases included meningioma,pituitary adenoma,neuroepithelial tumor,schwannoma,metastatic tumor,and hemangioblastoma.The meningioma cases consisted of 95.4%(103/108)cases of grade Ⅰ,3.7%(4/108)cases of grade Ⅱ,and only 1(1/108,0.9%)case of grade Ⅲ.Among the neuroepithelial tumor cases,the top three were glioblastoma,grade Ⅲ diffuse glioma,and ependymoma. Conclusions There are diverse CNS diseases confirmed by pathological diagnosis in Tibet,among which non-neoplastic diseases account for 1/3 of all the cases.Infectious and vascular diseases are the most common non-neoplastic diseases in Tibet,and tuberculosis and parasitic infections are relatively common.The types and proportion of brain tumors in Tibet are different from those in other regions of China,and meningioma is the most common in Tibet,with higher proportion than neuroepithelial tumor.

The change of interleukin -6, soluble interleukin - 6 receptor and soluble glycoprotein 130 levels in patients with lung injury caused by paraquat poisoning and its clinical significance / 中国医师进修杂志

Objective:To investigate the change of interleukin-6(IL-6), soluble interleukin-6 receptor(sIL-6R) and soluble glycoprotein 130(sgp130) levels in patients with lung injury caused by paraquat poisoning and its clinical significance.Methods:Fifty patients with paraquat poisoning and lung injury admitted to Ba′nan District People′s Hospital of Chongqing from December 2017 to December 2019 were selected as the observation group, and 30 healthy patients were selected as the control group. The serum levels of IL-6, sIL-6R and sgp130 in two groups was detected with double-antibody sandwich enzyme-linked immunosorbent assay and compared. Pearson correlation analysis was performed on the relationship between serum IL-6, sIL-6R and sgp130 and the acute physiological and chronic health status assessment(APACHE)- Ⅱ score of patients with lung injury caused by paraquat poisoning. The receiver operating characteristics (ROC) curve was used to analyze the diagnostic value of serum IL-6, sIL-6R and sgp130 on paraquat poisoning-induced lung injury.Results:The serum levels of IL-6, sIL-6R, and sgp130 in the observation group were significantly higher than those in the control group: (108.62 ± 11.39) ng/L vs. (57.41 ± 7.63) ng/L, (73.28 ± 6.94) ng/L vs. (45.13 ± 6.57) ng/L, (435.64 ± 36.52) mg/L vs. (281.71 ± 68.35) mg/L, and the differences were statistically significant ( P<0.05). The results of correlation analysis showed that the serum levels of IL-6, sIL-6R, and sgp130 in the observation group were significantly positively correlated with the APACHE-Ⅱ score ( r = 0.824, 0.937, 1.215, P<0.05). ROC curve analysis results showed that when serum IL-6, sIL-6R and sgp130 had the best diagnostic cut-off values of 83.96 ng/L, 68.51 ng/L and 367.42 mg/L respectively for the lung injury caused by paraquat poisoning, the sensitivity was 84.80%, 78.20% and 87.10%, and the specificity was 70.30%, 85.50% and 81.00%. Conclusions:The expression levels of IL-6, sIL-6R and sgp130 in serum are closely related to the severity of lung injury caused by paraquat poisoning, and IL-6, sIL-6R and sgp130 have good diagnostic value in lung injury caused by paraquat poisoning.

Analysis of DNM1L gene variant in a case of fatal encephalopathy caused by mitochondrial peroxidase division deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and disease-causing variants of a pediatric patient with fatal encephalopathy caused by mitochondrial peroxidase division deficiency, to identify the possible genetic causes of the disease and provide a basis for clinical diagnosis.@*METHODS@#A child with fatal encephalopathy caused by mitochondrial peroxidase division deficiency in West China Second Hospital of Sichuan University was selected. The clinical manifestations, laboratory findings and disease-causing variant were analyzed.@*RESULTS@#The main clinical symptoms of the patient were fever, headache and vomiting, followed by drug refractory epilepsy and progressive disturbance of consciousness. MRI showed deepening of sulcus, dilatation of bilateral ventricles, and multiple patch-like abnormal signals in paraventricular white matter, semioval center and subcortical white matter of bilateral frontal lobe. Gene detection showed a heterozygous missense variant c.1207C>T(p.Arg403Cys) in DNM1L, according to the American College of Medical Genetics and Genomics classification standards and guidelines for genetic variants, this variant was predicted to be pathogenic(PS1+PS2+PM2+PP3). After treated with gamma globulin, glucocorticoid, "mitochondrial cocktail therapy" and anti-epilepsy drugs, the condition of the patient was getting better, seizure attacks reduced and consciousness level improved.@*CONCLUSION@#The c.1207C>T variant in DNM1L gene may be the disease-causing variant for the patient, and the result of genetic testing provides a basis for the clinical diagnosis in this case.

Clinicopathological Analysis of Brain Metastatic Carcinoma in Tibet / 中国医学科学院学报

Objective To investigate the clinicopathological features and immunohistochemical phenotypes of brain metastatic carcinoma in Tibetan patients. Methods The clinical and pathological data of all patients with brain metastases from 2014 to 2020 in Tibet Autonomous Region People's Hospital were retrospectively analyzed,including 13 cases of brain metastatic carcinoma.All cases were diagnosed and classified by immunohistochemical staining. Results 13 cases(9 males and 4 females)of brain metastatic carcinoma,aged 26-62 years old,present with headache,dizziness,nausea and vomiting clinically.Four patients had a medical history of tumor,and among the 9 patients with no history of tumor,7 present space occupying lesions in both the brain and other organs.Imaging data could be found in 10 cases,including 4 cases of single lesion and 6 cases of multiple lesions.Primary tumors were identified in 11 cases(8 located in the lung,including 4 cases of adenocarcinoma,3 cases of small cell carcinoma,and 1 case of squamous cell carcinoma;1 case of urothelial carcinoma of the renal pelvis;1 case of thyroid papillary carcinoma;1 case of uterine choriocarcinoma),whereas the primary tumor was unknown for the other 2 cases(1 case of small cell carcinoma and 1 case of adenocarcinoma). Conclusions Brain metastatic carcinoma are more common among middle-aged and elderly people in Tibet.Most of the cases have no history of tumor,with the initial site at the brain metastatic lesions.The most common primary site is the lung,and the primary site of some cases is unknown.Multiple lesions are common in brain metastatic carcinoma,especially in the cerebral hemisphere.For older patients with multiple brain space occupying lesions,the possibility of brain metastatic carcinoma increases.

Clinicopathological Features and Expression of P504s,E-cadherin,Erythroblast Transformation-specific Related Gene and Estrogen Receptor in Prostate Adenocarcinoma in Tibet / 中国医学科学院学报

Objective To investigate the clinicopathological features and immunohistochemical expression of P504s,E-cadherin,erythroblast transformation-specific related gene(ERG)and estrogen receptor(ER)in prostate adenocarcinoma in Tibet.Methods The clinical data of 15 patients with prostate adenocarcinoma diagnosed by the Department of Pathology of Tibet Autonomous Region People's Hospital from September 2013 to September 2020 were analyzed retrospectively.All patients were assigned to prognostic grade groups based on Gleason score according to the WHO 2016 criteria.Immunostaining of P504s,E-cadherin,ERG,and ER was performed.Results The age of all 15 patients ranged from 61 to 86 years.The serum prostate specific antigen(PSA)concentration was ≥20 ng/ml in 12 patients and<20 ng/ml in 3 patients.Among the 15 patients,11 underwent needle biopsy,1 transurethral resection of the prostate,and 3 radical prostatectomy.Prognostic grouping results revealed 5 cases in grade groups 1-3,4 cases in grade group 4,and 6 cases in grade group 5.Immunohistochemistrically,15 cases(100%)were positive for P504s,E-cadherin and PSA;one case(7%)was positive for ERG;all cases were negative for P63,ER and CK34βE12.Thirteen cases were followed up for 2-48 months,with 2 cases treated with total prostatectomy and 11 cases with non-surgical treatment.Two cases were lost to follow-up. Conclusions Prostate adenocarcinoma is rare relatively in Tibet.The accuracy of diagnosis can be improved by using multiple immunohistochemical markers.The cases of grades 4 and 5 by pathological confirmed are relatively common in Tibet.P504s and E-cadherin are highly expressed in prostate adenocarcinoma patients in Tibet,while ERG presents low expression,ER is unexpressed.

Efficacy of intramedullary nail fixation for the tretament of tibial shaft fracture with difference approachs / 中国骨伤

OBJECTIVE@#To compare clinical effect of intramedullary nailing through suprapatellar, infrapatellar and paracpatellar approach in treating tibial shaft fracture.@*METHODS@#From June 2012 to June 2018, 36 patients with tibial shaft fracture were treated with intramedullary nails, and were divided into three groups according to surgical approach. Twleve patients were through suprapatellar approach, including 7 males and 5 females aged from 25 to 53 years old with an average of (37.8±11.4) years old;and 4 patients were type A, 4 patients were type B, and 4 patients were type C according to AO classification. Ten patients were through infrapatellar approach, including 6 males and 4 females aged from 19 to 56 years old with an average of (35.6±10.0) years old;and 3 patients were type A, 4 patients were type B, and 3 patients were type C according to AO classification. Forteen patients were through paracpatellar approach, including 8 males and 6 females aged from 21 to 58 years old with an average of (36.6±10.0) years old;and 4 patients were type A, 6 patients were type B, and 4 patients were type C according to AO classification. Operation time, intraoperative blood loss, fluoroscopy times, fracture healing time and complications among three groups were observed, and knee joint functions were evaluated by Lysholm score.@*RESULTS@#All patients were followed up from 12 to 18 months with an average of (15.0±3.0) months. There were no difference in intraoperative blood loss and fracture healing time among three groups (@*CONCLUSION@#intramedullary nailing through suprapatellar for the treatment of tibial shaft fracture is benefit for fracture healing and recovery of knee joint function, while infrapatellar and paracpatellar approach have advantages in exposure of insertion point. We should select approach reasonably according to our experience.

Role of Erbin in muramyl dipeptide-induced inflammatory responses in macrophages of mice / 中华麻醉学杂志

Objective:To evaluate the role of ErbB2-interacting protein (Erbin) in muramyl dipeptide (MDP)-induced inflammatory responses in the macrophages of mice.Methods:Erbin gene knockout RAW264.7 cell line (Erbin -/ -RAW264.7) was constructed by CRISPR/CAS9 gene-editing technology.RAW264.7 cells were cultured in vitro.Each type of cells was divided into 2 groups ( n=16 each)by a random number table method: RAW264.7 group, RAW264.7 plus MDP group, erbin -/ -RAW264.7 group, and erbin -/ -RAW264.7 plus MDP group.In each MDP group, cells were incubated with 10 μg/ml MDP for 6 h, then immunofluorescence was used to determine the expression of nuclear factor kappa B (NF-κB) p65, and the concentrations of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the culture medium were determined by enzyme-linked immunosorbent assay. Results:Compared with RAW264.7 group, the concentrations of TNF-α and IL-6 in the culture medium were significantly increased( P<0.05), NF-κB p65 moved to the nucleus, and the red fluorescence area was increased in RAW264.7+ MDP group.Compared with RAW264.7+ MDP group and Erbin -/- RAW264.7 group, the concentrations of TNF-α and IL-6 in the culture medium were significantly increased ( P<0.05), NF-κB p65 moved more markedly to the nucleus, and the red fluorescence area was increased in Erbin -/-RAW264.7+ MDP group. Conclusion:Erbin inhibits MDP-induced inflammatory responses in macrophages through inhibiting the activity of NF-κB p65 in mice.

Effects of calcium-binding sites in the S2–S3 loop on human and Nematostella vectensis TRPM2 channel gating processes / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

As a crucial signaling molecule, calcium plays a critical role in many physiological and pathological processes by regulating ion channel activity. Recently, one study resolved the structure of the transient receptor potential melastatin 2 (TRPM2) channel from Nematostella vectensis (nvTRPM2). This identified a calcium-binding site in the S2–S3 loop, while its effect on channel gating remains unclear. Here, we investigated the role of this calcium-binding site in both nvTRPM2 and human TRPM2 (hTRPM2) by mutagenesis and patch-clamp recording. Unlike hTRPM2, nvTRPM2 cannot be activated by calcium alone. Moreover, the inactivation rate of nvTRPM2 was decreased as intracellular calcium concentration was increased. In addition, our results showed that the four key residues in the calcium-binding site of S2–S3 loop have similar effects on the gating processes of nvTRPM2 and hTRPM2. Among them, the mutations at negatively charged residues (glutamate and aspartate) substantially decreased the currents of nvTRPM2 and hTRPM2. This suggests that these sites are essential for calcium-dependent channel gating. For the charge-neutralizing residues (glutamine and asparagine) in the calcium-binding site, our data showed that glutamine mutating to alanine or glutamate did not affect the channel activity, but glutamine mutating to lysine caused loss of function. Asparagine mutating to aspartate still remained functional, while asparagine mutating to alanine or lysine led to little channel activity. These results suggest that the side chain of glutamine has a less contribution to channel gating than does asparagine. However, our data indicated that both glutamine mutating to alanine or glutamate and asparagine mutating to aspartate accelerated the channel inactivation rate, suggesting that the calcium-binding site in the S2–S3 loop is important for calcium-dependent channel inactivation. Taken together, our results uncovered the effect of four key residues in the S2–S3 loop of TRPM2 on the TRPM2 gating process.

Comparison of clinical effect between autogenous semitendinosus and allogenic tendons for anatomical reconstruction of anterior talofibular ligament and calcaneofibular ligament under arthroscopy / 中华骨科杂志

Objective@#To compare the clinical effects of autologous semitendinosus tendon and allogenic tendon arthroscopic anatomical reconstruction of anterior talofibular ligament (ATFL) combined with calcaneofibular ligament (CFL) in the treatment of chronic lateral ankle instability.@*Methods@#A retrospective analysis was made of 55 patients with chronic lateral ankle instability who underwent arthroscopic reconstruction of ATFL combined with CFL from January 2012 to June 2017. A total of 28 cases were treated with autologous semitendinosus tendon (autologous group), including 19 males and 9 females, with an average age of 28.5±8.03 years (range, 16-46 years). A total of 27 cases were treated with allogenic tendon (allogenic group), including 17 males and 10 females, with an average age of 27.48±7.89 years (range, 16-46 years). ATFL/CFL was reconstructed by the same method in both groups. The reconstruction methods were the same between the groups. The talus and calcaneus were fixed with absorbable compression nails.@*Results@#The operation duration in the autologous group was 94.07±7.83 min, which was longer than that in the allogeneic group 63.56±7.96 min (t=14.51, P<0.001). Fever days 5.26±0.90 days in allogeneic group were longer than 2.46±0.74 days in autologous group (t=-12.55, P<0.001). Wound healing duration in allogeneic group was 13.44±3.33 days longer than that in autologous group 10.32±2.34 days (t=-4.01, P<0.001). In the autologous group, 28 cases were followed up for 34.54±16.04 months, and 27 cases in the allograft group were followed up for 42.74±17.79 months. The mean AOFAS score improved from 63.64±11.20 before operation to 90.21±4.48 after operation in the autologous group, and that improved from 63.93±10.59 before operation to 89.56±5.15 after operation in the allogeneic group with no significant difference between the two groups after operation (t=0.506, P=0.615). The mean VAS score decreased from 5.79±1.79 before operation to 1.54±1.35 after operation in the autologous group, and from 5.89±1.78 before operation to 2.04±1.32 after operation in the allogeneic group. There was no significant difference between the two groups after operation (t=-1.396, P=0.168). Tegner score increased from 4.07±1.39 to 6.43±1.14 in the autologous group and from 3.85±1.06 to 6.52±0.85 in the allogeneic group with no significant difference between the two groups after operation (t=-0.333, P=0.740). Stress radiographic showed that the talar tilt angle decreased from 15.60°±3.86° to 6.01°±2.64° in the autologous group, 16.99°±3.78° to 7.14°±3.34° in the allogeneic group, and there was no significant difference between the two groups after operation (t=-1.382, P=0.171). Anterior talar displacement reduced from 10.82±3.12 mm to 4.03±1.69 mm in the autologous group, from 10.10±2.02 mm to 4.17±1.52 mm in the allogeneic group, and there was no significant difference between the two groups after operation (t=-0.326, P=0.746). No donor tendon dysfunction was found in the autologous group. At the end of follow-up, there was no difference in ankle dorsiflexion, plantar flexion and hind foot mobility between autologous group and allogeneic group.@*Conclusion@#Arthroscopic autologous tendon and allogeneic tendon reconstruction of AFTL combined with CFL can obtain satisfactory short-term results. The autologous tendon group was superior to the allogeneic group in terms of fever, wound healing time. However, there was no significant difference in clinical effects between the two groups.

Efficacy of 755 nm semiconductor laser during the auricular reconstruction for hair removal / 中华整形外科杂志

Objective@#To compare the clinical efficacy and patient satisfaction of 755 nm semiconductor laser for hair removal during different stages of auricular reconstruction.@*Methods@#From July 2016 to September 2018, 86 patients who had ear reconstruction underwent 755 nm semiconductor laser for auricle hair removal in plastic surgery department of Tongji hospital affiliated to Tongji medical college of Huazhong university of science and technology. There were 39 males and 47 females with an average age 12 years old(from 6 to 28 years old). 28 cases were left ear, 58 cases were right ear. With random grouping, 40 patients underwent auricle hair removal treatment after posterior ear tissue expander implantation (post-operation of stage Ⅰ depilation group) and 46 patients underwent treatment after auricular reconstruction (post-operation of stage Ⅱ depilation group). Auricle hair removal treatments(pulse width 10-20 ms, wave length 755 nm, spot size 10 mm×15 mm, energy density 4-8 J/cm2) were respectively started at different intervention time. Each treatment time were 5-10 minutes. The end of the treatment was slight redness or edema of the local hairy follicle. The treatment was repeated every 4 weeks with a total of 5 times. The number of adverse reactions was recorded as while as the hair density, hair clearance rate and patient satisfaction before treatment and 6 months after the 5th depilation.@*Results@#Patients in both groups successfully were completed the treatment and were followed up to about 6 months (23 to 25 weeks) after the last depilation treatment. There were only 2 cases with scratch in skin preparation and 2 cases with blisters in the postoperative of stage Ⅱ group. None of the other patients had adverse reactions. Hair density after treatment (27.63±7.75 bar/cm2) was less than before treatment (84.55±13.68 bar/cm2) in post-operation of stage Ⅰ depilation group. Hair density after treatment was 40.52±5.92 bar/cm2 in post-operation of stage Ⅱ depilation group, less than before treatment (74.78±11.19 bar/cm2). The differences were statistically significant (both P<0.001). After hair removal, the hair density of post-treatment in the post-operation of stage Ⅰ depilation group was less than the post-operation of stage Ⅱ depilation group. The difference was statistically significant (P=0.000). The hair clearance rate of the post-operation of stage Ⅰ (67.32%) was higher than the post-operation of stage Ⅱ(45.81%). The difference was statistically significant (P<0.001). Patients’ satisfaction was 87.5% in the post-operation of stage Ⅰ and 69.5% in the post-operation of stage Ⅱ. The former was superior to the latter.@*Conclusions@#Auricle hair removal with semiconductor 755 nm laserstarted at stage Ⅰ that posterior ear tissue expander was implanted has more favorable clinical efficacy, and higher patient’s satisfaction rate.