OBJECTIVE To investigate the genetic causes of deaf patients in a special educational school of Chifeng city, Inner Mongolia by SLC26A4 whole gene sequencing. This study focused on analyzing mutations of coding sequence of SLC26A4 gene and their relevant phenotype. METHODS DNA were extracted from peripheral blood of 134 deaf patients of Chifeng special educational school and 100 normal hearing controls in Northern China. SLC26A4 gene mutation was analyzed by direct sequencing for its 20 coding exons. All individuals found with SLC26A4 mutation were given temporal bone CT scan, and those with confirmed enlarged vestibular aqueduct and/or other malformation of inner ear were then given further ultrasound scan of thyroid and thyroid hormone assays. RESULTS The sequencing results revealed 32 cases carried SLC26A4 mutation. Twenty-nine cases underwent temporal bone CT scan. Twentycases were confirmed to have malformation of inner ear by CT scan (eighteen were EVA, one was EVA and other inner ear malformation and one was Mondini Syndrome). The shape and function of thyroid were confirmed to be normal by ultrasound scan of thyroid and thyroid hormone assays in nineteen of these 20 patients except one who had cystoid change in the right side of thyroid. Twelve types of novel variants of SLC26A4 gene were found. CONCLUSION Byscreening SLC26A4 gene coupled with temporal bone CT scan ,we could determine genetic cause related to this gene up to 14.93 % of deaf patients in special educational school of Chifeng city. SLC26A4 is another common gene besides GJB2 that cause deafness in this area. The discovery of novel variants of SLC26A4 gene makes the mutational and polymorphic spectrum more plentiful in Chinese population.

Objective To evaluate the value of 99Tcm-MDP uptake by left femoral neck for diagnosing osteopomsis.Methods A total of 58 cases (23 males,35 females,mean age:(66.15±8.45) years) with spondyloarthmpathies from May to December of 2012 were selected.Serum concentrations of type Ⅰ collagen telopeptide (sCTX-1) and bone ALP (BALP) were determined.All patients underwent dual-energy X-ray absorptiometry (DXA) to detect bone mineral density (BMD).According to the T scores,patients were divided into 2 groups:normal group (NG) (T＞-1.0) and osteoporosis group (OG) (T≤-2.5).99TcmMDP bone scan was further performed.The average radioactive ratio of the left femoral neck to the medial soft tissue of left femur (T/N) was measured.Data differences between the 2 groups were compared by twosample t test and Pearson correlation analysis.Results According to BMD,13 patients (7 males,6 females) were included in NG and 28 patients (10 males,18 females) were included in OG.The mean ages of OG and NG were significantly different ((68.82± 10.41) years vs (62.46± 11.77) years; t =3.560,P＜0.05).The BMD of left femoral neck in OG was significantly lower than that in NG ((0.67±0.08) g/cm2 vs (0.91±0.10) g/cm2 ; t=9.917,P＜0.01).Although BALP level of OG was significantly higher than that of NG ((35.92±11.58) U/L vs (22.38±6.34) U/L; t=-3.397,P＜0.05),no significant difference was observed on sCTX-1 between the 2 groups (t=-0.463,P＞0.05).T/N ratio of OG (11.63±6.22) was higher than that of NG (9.74±4.44) (t =-3.027,P＜ 0.05).There were significant correlations between the T/N ratio of the left femoral neck and the sCTX-1 and BALP concentrations (r=0.376,0.483,both P＜0.01).No correlations between the T/N ratio of the left femoral neck and age,BMI and BMD were observed (r=-2.031,-0.017,0.134,all P＞0.05).Conclusion The uptake ratio of the left femoral neck in 99Tcm-MDP bone scan could evaluate the metabolism of bone,and it is useful for the early diagnosis of osteoporosis.

Adolescent ; Child ; Diagnosis, Differential ; Dystonic Disorders ; diagnosis ; drug therapy ; physiopathology ; Female ; Humans ; Male

OBJECTIVETo explore the effect of the mixed liquor of danshen and magnesium sulfate injection on inflammatory reaction caused by autoimmune response of rabbits with lumbar intervertebral disc herniation.

METHODSSixty rabbits were divided into blank group (10 rabbits), sham operation group (10 rabbits), model group (40 rabbits) according to method of random digits table. Then model group was divided into made group (group A, 10 rabbits), normal saline group (group B, 10 rabbits), aescin natrium group (group C, 10 rabbits) and danshen and magnesium sulfate injection group (group D,10 rabbits). After model success of lumbar intervertebral disc herniation, different drugs were given to rabbits with lumbar intervertebral disc herniation by ear margin vein. The rabbits of the group C,B,D were respectively given aescin natriu (0.5 mg/kg), normal saline (5 ml/kg), danshen and magnesium sulfate injection (2.0 mg/kg). The rabbits of blank group, sham operation group and group A were not given any disposal. The IgG and IgM level in serum of different groups were determined with ELISA method in fourteen day after model success and drugs given.

RESULTSThe level of IgG and IgM in the group A was higher than that of blank group and sham operation group (P < 0.05). The level of IgG and IgM in the group D was lower than that of group B,C (P < 0.05).

CONCLUSIONThe mixed liquor of danshen () and magnesium sulfate injection could inhibit inflammatory reaction caused by autoimmune response of lumbar intervertebral disc herniation,which provides a new alternative for lumbar intervertebral disc herniation.

Animals ; Disease Models, Animal ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Injections ; Intervertebral Disc Displacement ; blood ; drug therapy ; immunology ; Magnesium Sulfate ; administration & dosage ; Male ; Phenanthrolines ; administration & dosage ; Rabbits ; Random Allocation ; Salvia miltiorrhiza ; chemistry

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

PCR method was used to introduce the code sequence of Factor Xa cleavage site to the 5′ end of cecropin CMIV mutant gene X, then the gene was cloned into the expression vector pGEX-KG, and was highly expressed in E. coli BL21 by IPTG induction. The fusion protein was purified by affinity-chromatography and was cleaved by Factor Xa. Cecropin X with antibacterial activity was obtained after purified by ion-exchange chromatography.

Objective To compare intrarenal pelvic pressure or endoureteral pressure and infection index between perfusion pump and low pressure of gravity drip during percutaneous nephrolithotomy (PCNL). Methods From 2015 April to 2017 June, 107 patients with ureteral or renal calculus were randomly divided into two groups, among whom 46 cases underwent perfusion pump PCNL and 61 cases underwent low pressure gravity drip PCNL. No statistical significance of preoperative variables was found between the two groups such as age, gender,preoperative status of infection,status of hydrpnephrosis,size and location of stone (P＞0.05).A 5Fr ureteral catheter was positioned into the renal pelvic or ureter,and the intrarenal pelvic or endoureteral pressure was measured by anesthesia monitor during PCNL for all patients.We recorded and compared removing calculus time, postoperative hemoglobin changing, fever rate, procalcitonin abnormal rate, white blood cell counts and calculi clearance rate.Results The average pelvic or endoureteral pressures in the group undergoing perfusion pump and the one undergoing low pressure gravity drip were (22.7±4.6) mmHg VS (29.8±5.3) mmHg and the maximum pressure were (28.8 ±6.56) mmHg VS (50 ±9.25) mmHg.The statistics was significantly different (P＜0.05).Compared with perfusion pump group, the group undergoing low pressure gravity drip had significant differences in fever rate [4.9%(3/61) VS.17.3%(8/46) ], procalcitonin abnormal rate [3.2%(2/61) VS. 15.2%(7/46) ] and white blood cell counts abnormal rate[9.8%(6/61) VS.28.26%(13/46) ] (P＜0.05). However,no significant difference was seen in postoperative hemoglobin changing[(8.3±3.7) g/L VS.(7.2 ± 3.3) g/L] (P＞0.05) and the time of removing calculus [(42.4 ±14.5) min VS (43.6 ±13.5) min] (P＞0.05) .Conclusions Compared with perfusion pump, low pressure gravity drip PCNL maintains lower renal pelvic or endoureteral pressure, which is less than reflux limit during calculi fragmentation. It might be contributed to reduce the postoperative fever rate, white blood cell counts abnormal rate and procalcitonin abnormal rate. Hemoglobin changing and the time of removing calculus show no obvious disadvantage.

BACKGROUNDAs a time-dependent antibiotic, the time of cefazedone concentration exceeds the minimum inhibitory concentration (MIC) is the key pharmacokinetic-pharmacodynamic (PK-PD) variable associated with the killing of pathogens. The purpose of the study was to evaluate the clinical regimen rationality of intravenous cefazedone sodium in the treatment of community-acquired pneumonia (CAP) by PK/PD study.

METHODSTen patients with mild to moderate CAP were enrolled to receive intravenous cefazedone sodium (2 g q12 h) for 7-14 days. Blood samples were collected in any day during day 5-7. Sputum specimens were collected before treatment for bacteria isolated, and susceptibility to cefazedone determined. PK-PD analysis was performed using the noncompartmental analysis of Phoenix WinNolin software (version 6.1, Pharsight Corporation, CA, USA). The maximal time above MIC (ƒT > MIC) was calculated, and its correlation with clinical efficacy was analyzed.

RESULTSAll 10 patients completed the study and 8 of them were cured. Six strains were isolated from patients before treatment (one for each patient) and all susceptible to cefazedone. Five patients of six in culture positive group were cured. All pathogens were cleared at the end of therapy. The MICs were between 0.25 and 1 mg/L. The main PK parameters were C max 175.22 ± 36.28 mg/L; T½ 1.52 ± 0.23 h; AUC (0-∞) 280.51 ± 68.17 mg·L -1·h -1 ; CL 7.37 ± 1.84 L/h; Vd 16.06 ± 4.42 L. The average ƒT > MIC was 55.45 ± 8.12%.

CONCLUSIONSIntravenous injection of cefazodone sodium with 2 g q12 h dosage regimen is used in the treatment of CAP caused by sensitive bacteria, either ƒT > MIC or clinical efficacy shows that such dosing regimen is reasonable.

Administration, Intravenous ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; administration & dosage ; pharmacokinetics ; therapeutic use ; Cefazolin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Community-Acquired Infections ; drug therapy ; metabolism ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Young Adult

Alzheimer's disease(AD) is a neurodegenerative disease that has no effective drug to cure it. Studies in several AD models have shown that Erigeron breviscapus and its active ingredients(scutellarin and caffeoylquinic acid) could improve/enhance the learning and memory ability, and the mechanisms are associated with inhibiting amyloid β(Aβ) production, aggregation, fibrosis and Aβ neurotoxicity toxicity, regulating cholinergic nervous system, inhibiting oxidative stress and inflammation, inhibiting tau hyperphosphorylation, improving mitochondrial function, and resisting neuronal apoptosis. This article systematically reviewed the research progress of E. breviscapus and its active ingredients for treatment of AD in AD models, in the expectation of providing references for further development of E. breviscapus's medicinal potential.
Alzheimer Disease ; Amyloid beta-Peptides ; Erigeron ; Humans ; Neurodegenerative Diseases

Objective To investigate the etiology of patients with severe to profound hearing loss and to identify the ratio of hereditary hearing loss in Chffeng area in Northern China. Methods DNA were extracted from peripheral blood of 134 deaf patients from Chifeng special educational school and 100 normal hearing controls in Northern China. Audiology examinations showed that all patients had severe to profound bilateral sensorineural hearing impairment. Sequence analysis of the whole coding areas of GJB2, GJB3, GJB6, SLC26A4, mtDNA12SrRNA and mtDNAtRNASer(LCN) were performed. Individuals carrying SLC26A4 mutation were given further temporal bone CT scan. Results The ratio of hearing loss related to genetic factors in this population was 60. 45% (81/134). About 33.58% (45/134) of the patients were given accurate genetic diagnosis. GJB2 mutations were responsible for approximately 17.16% of the cases in ChiFeng area. By screening SLC26A4 followed by temporal bone CT scan, we diagnosed 20 cases of enlarged vestibular aqueduct (EVA) and/or other inner ear malformation. SLC26A4 mutations account for about 14. 93% of the cases. The aminoglycoside-related mtDNA 1555A > G mutation accounted for 0.76% of the eases in Chifeng area. In addition, another 13.43% (18/134)of the cases carried heterozygous GJB2 mutation and their hearing loss may be related to GJB2. 6. 72% (9/134)of the cases carried heterezygous SLC26A4 mutation who were not found EVA by temporal bone CT or not took CT examination for some reasons. However, their hearing loss may also be SLC26A4-related. About 2. 24% (3/134)of the cases carried mtDNA 12SrRNA 1095 T > C which may also be an aminoglycoside-related mutation and very likely be the cause of hearing loss. GJB3 might participate in the pathomechanism of hearing loss in 1.49% (2/134) of the patients. GJB6 mutation was not detected in this population. Conclusions The ratio of hearing loss related to genetic factors in the sample drawing population from Chifeng was 60. 45% (81cases). GJB2 is the most common gene and SLC26A4 is the second common gene next to GJB2 that cause deafness in this area.