Objective:To observe any effect of repeated transcranial magnetic stimulation (rTMS) in the treatment of diabetic peripheral neuropathic pain (DPNP).Methods:Eighty-six persons with type 2 diabetes mellitus and DPNP were randomly divided into an observation group and a control group, each of 43. Both groups were given basic treatment to control plasma glucose and blood pressure, while the observation group was additionally provided with daily 10Hz rTMS of the primary motor cortex (M1 area) of the non-dominant hand 5 days a week for 4 weeks. Before and after the treatment, pain in both groups was evaluated using a visual analog scale (VAS) and the Patient′s Global Impression Change scale (PGIC). The motor conduction velocity (MCV) and sensory conduction velocity of the median and the common peroneal nerves were also tested.Results:After treatment, the average VAS pain rating and PGIC score of the observation group were significantly lower than the control group′s averages and those before treatment. The observation group′s treatment effectiveness rate (79.07%) was then much better than that of the control group (23.26%). After the treatment, the average MCV of the median and common peroneal nerves of the observation group (47.65±1.94 m/s and 46.98±3.26 m/s, respectively) were significantly faster than before treatment, and those of the control group.Conclusions:rTMS based on routine intervention can significantly relieve DPNP and promote the recovery of injured nerves, bettering diabetics′ physical condition and life quality.

Objective:To explore clinical evaluation and genetic analysis of patients with idiopathic hypogonadotropic hypogonadism (IHH).Methods:The clinical data and phenotypes of 22 patients with IHH diagnosed and treated in our department were reviewed and analyzed. Whole-exome sequencing(WES)and Sanger method were used for variant analysis and verification.Results:Among the 22 cases of IHH probands, 12 cases of Kalman syndrome (KS) and 10 cases of IHH (nIHH) with normal sense of smell. On physical examination, males showed short penis, small testicles, small or inconspicuous laryngeal knots, and a sharp voice. Mammary gland development, mammary gland dysplasia, primary amenorrhea, etc. in women. Sex hormone examination: Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) levels are reduced or at the lower limit of normal. There were nine missense variants of CHD7 gene in 8 patients. Based on the American College of Medical Genetics and Genomics guidelines, the c. 307T>A(p.Ser103Thr), c.3143G>A(p.Gly1048Glu), c.6956G>T(p.Arg2319Leu) and c. 3145A>T(p.Ser1049Cys) variants of CHD7 gene were predicted to be likely pathogenic (PS1+ PP1+ PM2, PM2+ PM6+ PP2+ PP3, PM2+ PM5+ PM6+ PP2+ PP3 and PM2+ PM6+ PP2+ PP3), the remaining 14 cases of IHH patients had negative genetic screening. Conclusion:CHD7 gene variants may be related to IHH disease.

Patellofemoral osteoarthritis (PFOA) is a subtype of knee osteoarthritis that has gained popularity in recent years due to its high prevalence and disease burden. The National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) and the Joint Surgery Branch of the Chinese Orthopaedic Association, together with the editorial department of the Chinese Journal of Orthopaedics, convened a panel of orthopaedic experts to come up with guidelines. Subsequently, the Chinese clinical practice guideline for patellofemoral osteoarthritis (2020 edition) was officially released in September 2020. This is of utmost importance in standardizing the clinical diagnosis and treatment of PFOA in China. The present guideline focused on the diagnosis (symptoms, signs and imaging changes), non-surgical interventions (primary treatment and pharmacotherapy) and surgical interventions (repair and reconstruction) of PFOA. The present interpretation aims to address key emerging clinical issues in the diagnosis and treatment of PFOA in China.

OBJECTIVE: To explore the genotype-phenotype correlation among 18 patients with 21-hydroxylase deficiency (21-OHD). METHODS: PCR-Sanger sequencing was used to analyze the 10 exons and flanking regions of the CYP21A2 gene among the 18 patients and 20 healthy controls. RESULTS: Seventeen patients had variants of the CYP21A2 gene. Eight patients (44.4%, 8/18) carried homozygous variants including p.Ile 173Asn (62.5%, 5/8), p.Pro31Leu (25.0%, 2/8), and IVS2-13A/C>G (12.5%, 1/8), respectively. Six patients (33.3%, 6/18) carried compound heterozygous variant, among which IVS2-13 A>G+p.Ile 173Asn were most common (50.0%). 94.4% (34/36) of the variant were pathogenic, with the most common variants being p.Ile173Asn (41.7%), IVS2-13A/C>G (19.4%), and p.Ile173Asn (7.5%). No variant was identified among the 20 healthy controls. CONCLUSION The majority of 21-OHD patients carried CYP21A2 gene variants in homozygous or compound heterozygous forms, among which the p.Ile173Asn was the most common one. There is a strong correlation between the genotypes and clinical phenotypes.
Adrenal Hyperplasia, Congenital ; genetics ; Genotype ; Humans ; Mutation ; Phenotype ; Steroid 21-Hydroxylase ; genetics

OBJECTIVE: To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD). METHODS: Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees. RESULTS: Gene sequencing has identified a homozygous c.985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c.1459_1467del9 (p.D487_F489del) and c.1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c.985_987delTACinsAA(Y329Kfs) mutation. CONCLUSION Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c.985_987delTACinsAA(Y329Kfs) is the most common. The c.1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.
Adrenal Hyperplasia, Congenital ; genetics ; Exons ; Female ; Humans ; Male ; Mutation ; Pedigree ; Steroid 17-alpha-Hydroxylase ; genetics

Objective: To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD). Methods: Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees. Results: Gene sequencing has identified a homozygous c. 985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c. 1459_1467del9 (p.D487_F489del) and c. 1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c. 985_987delTACinsAA(Y329Kfs) mutation. Conclusion Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c. 985_987delTACinsAA(Y329Kfs) is the most common. The c. 1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.

Objective: To evaluate the clinical application of bronchial washing fluid (BWF) in the detection of epidermal growth factor receptor (EGFR) gene mutation in lung cancer patients during diagnostic bronchoscopic procedure. Methods: Patients with suspected lung cancer lesions but failed to be identified as malignancy by rapid on-site cytologic evaluation (ROSE) were enrolled. Performed blocker PCR for EGFR mutation detection using the supernatant and cell pellet of BWF samples and compared the detective results to the EGFR mutation status detected using histologic tumor samples. Results: A total of 85 BWF and paired histological samples were collected at Fudan University Affiliated Zhongshan Hospital from October 2016 to June 2017. There were 46 male and 39 female, with a mean age of 61 years (range 30-87 years). Thirty-one patients had benign diseases and 54 patients had primary lung cancer. Among these 54 lung cancer patients, the diagnoses were made basing on bronchoscopic biopsy samples in 31 patients. The detection rate of EGFR gene mutation in BWF samples was 100.0% concordant with that using histological samples.Another 23 cases whose bronchoscopic biopsy failed to establish malignant diagnoses were further identified by other sampling methods including surgical resection, lung biopsy, etc. A total of 15 patients were identified as EGFR mutated type by pathologic detection or clinically effect assessment, and BWF could detect 11 of them, accounting for 11/15 of all cases. Overall, BWF had achieved an overall accuracy of 95.3% (81/85) comparing to paired tumor histologic samples. Conclusions BWF is an effective complementary specimen to bronchoscopic biopsy samples in EGFR gene mutation detection in patients with suspected lung cancer lesion and negative biopsy results evaluated by ROSE during bronchoscopy.

Objective To investigate the change of CD35 expression on neutrophils in the peripheral blood and the relationship between the change and disease activity in patient with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV).Methods Forty untreated patients with active MPO-AAV(patient group)and forty healthy volunteers (control group) were enrolled into this study,and Bermingham vasculitis activity score (BVAS) for every patient was recorded.Flow cytometry (FCM) was employed to detect the CD35 and MPO expression on the neurtrophil,and enzyme linked immunosorbent assay (ELISA) was taken to test the levels of autoantibody against MPO-Antineutrophil cytoplasmic antibody (MPO-ANCA),fragment a from the activated complement factor B (Ba) and MPO in peripheral blood from both group.All test results were compared between the 2 groups by t test,Non-parametric test,Spearman correlation analysis.In addition,the relations among the laboratory results and the relationship between BVAS and the laboratory results were analyzed respectively.Results Compared with the control group,the expression level,which was represented as mean flourscence indensity (MFI),of CD35 and neutrophil membrane MPO on peripheral blood neutrophils was significantly increased [(2 014±968) vs (1 454±511),t=3.024,P=0.002 and (709±244) vs (580±158),t=2.806,P＜0.01,respectively],and the MPO expression level in neutrophils was significantly lower [(1 525±1 033) vs (3 196±2 126),t=-4.468,P＜0.01].Ba and MPO levels in serum of the patient group was significantly higher than that in the control group [37.89(26.17,63.14) μg/L vs 27.99(18.64,46.52) μg/L,Z=-2.521,P=0.012 and 546.16(450.55,729.96) U/L vs 327.93(279.02,365.10) U/L,Z=7.121,P＜0.01,respectively].In patient group,the expression level of CD35 had a significant positive relationship with peripheral blood neutrophil count (r=0.573,P＜0.01),serum Ba (r=0.433,P=0.005) and BVAS (r=0.368,P=0.020),respectively,whereas,there was a negative correlation between the MPO expressed on the neutrophils and that in the neutrophils (r=-0.458,P=0.003),and a positive relationship between MPO-ANCA and BVAS (r=0.351,P=0.026).Conclusion There is significant increased expression of CD35 on the neutrophil of patient with MPO-AAV,which might protect the neutrophil from destruction by the activated complement alternative pathway,and more neutrophils consequently contribute to the MPO-AAV pathogenesis.Inhibition of CD35 expression might become one of the potential new pathways for the treatment of MPO-AAV.

Objective To investigate the effect and its underlying mechanism of Linagliptin on mild cognitive impairment (MCI) in elderly type 2 diabetes mellitus (T2DM) patients.Methods Montreal Cognitive Assessment(MoCA)scale was used to prospectively screen T2DM patients for MCI in our hospital from December 2016 to June 2017,and a total of 98 elderly T2DM patients with MCI were recruited.They were randomly divided into the linagliptin group(Linagliptin + metformin,n=50)and the non-linagliptin group(gliclazide + metformin,n =48).Serum fasting plasma glucose (FPG),glycosylated hemoglobin(HbAlc),blood lipids and amyloid β-protein 1-42 (Aβ1-42) levels were determined,and MoCA score and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated,and were compared between the two groups before and after 24 weeks of treatment.Results In the linagliptin group,serum FPG,HbA1c,HOMA-IR,Aβ1-42 levels were significantly decreased and MoCA score was increased after 24 weeks of treatment as compared with pre-treatment [(7.29± 1.00) mmol/L vs.(9.16 ± 1.60) mmol/L,(7.19 ± 0.99) ％ vs.(9.36 ± 1.07) ％,(3.05 ± 1.12) vs.(4.05±1.30),(0.463±0.093)g/L vs.(0.528±0.110)g/L,(24.48± 1.18) vs.(23.22± 1.37),all P＜0.05].In the non-linagliptin group as control,FPG and HbA1c levels were decreased after 24 weeks of treatment as compared with pre-treatment[(7.23±1.09)mmol/L vs.(9.20± 1.75) mmol/L,(7.23±1.03)％ vs.(9.69± 1.18)％,both P ＜ 0.05],while there was no significant difference in HOMA IR,Aβ1-42 level and MoCA score[(3.95 ± 1.00) vs.(4.19± 1.13),(0.517± 0.113)g/L vs.(0.526±0.119)g/L,(23.21±1.18) vs.(23.00±1.32),all P＞0.05].It is worth to pay close attention to the key discovery of this paper that HOMA-IR and Aβ1-42 levels were significantly lower and MoCA score was significantly higher in the linagliptin group than in the non-linagliptin group after 24 weeks of treatment(all P＜0.05).Conclusions Linagliptin as one of DPP-4 enzyme inhibitors can improve the cognitive function in elderly patients with T2DM,which might be relevant to reducing serum Aβ level and improving HOMA-IR.DPP-4 enzyme inhibitor may be a good option for treatment of mild cognitive dysfunction in T2DM patients in the future.

Objective To explore the relationship between visfatin and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods A perspective study involving 75 hospitalized T2DM patients were divided into groups with(MCI,n=35)and without (NMCI,n =40)mild cognitive impairment.Another 30 non-diabetic patients were chosen as normal control(NC).Fasting plasma levels of glucose (FPG),insulin (FINS),lipid,glycosylated hemoglobin (HbAlc),HOMA-IR and visfatin were measured and calculated.Results The serum visfatin level was higher in MCI(28.81±3.32)μg/L than in NMCI(20.69±3.40)μg/L and NC(19.06±2.35)μg/L (F=96.491,P＜ 0.01).Visfatin was negatively correlated with Montreal Cognitive Assessment (MoCA) total score (MoCA-TS) (r =-0.646,P ＜ 0.01),but positively correlated with course of disease,waist hip ratio,FPG,HbAlc,FINS,HOMA-IR and triglyceride (r=0.282,0.276,0.318,0.496,0.339,0.433,0.309,P＜0.05 or P＜0.01).MoCA-TS was negatively correlated with course of disease,HbAlc,HOMA-IR,triglyceride,total cholesterol,low density lipoprotein cholesterol (r =-0.582,-0.365,-0.234,-0.330,0.277,-0.238,P＜0.05 or P＜0.01),but positively correlated with high density lipoprotein cholesterol(r=0.290,P＜0.05).Higher values of visfatin(OR =3.246,P＜0.01),HbAlc(OR=2.308,P＜0.01)and course of disease(OR=1.634,P＜0.05)were the risk factors for MCI.Conclusions The elevated visfatin level might be a risk factor for MCI in T2DM patients.