A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

Ultrasonographic assessment and differentiation of spontaneous degenerating cystic thyroid nodules and papillary thyroid carcinomas / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the features of degenerating cystic thyroid nodules (DCTN) on conventional ultrasound and contrast-enhanced ultrasound (CEUS), and to explore the differentiation between DCTN and papillary thyroid carcinomas (PTC). Methods: A total of 46 DCTN (39 cases, including 12 males and 27 females, with an age range of 25 to 76 years) and 36 PTC (32 cases, including 8 males and 24 females, with an age range of 23 to 68 years) diagnosed via fine- needle aspiration (FNA) or surgery from February 2019 to January 2020 in the First Affiliated Hospital of Nanchang University were enrolled. The size, shape, margin, echogenicity, presence of shadowing, calcification and vascularity of DCTN and PTC were retrospectively evaluated, and 28 DCTN and 30 PTC underwent CEUS were separately analyzed and compared.The t test, χ² test or Fisher's exact test were implemented to compare the features of ultrasound among the two groups. The binary Logistic regression test was performed to determine whether the feature whose difference was statistically significant was an independent predictive risk factor. Results: A univariate analysis indicated that DCTN more frequently showed wider-than-tall shapes, marked hypoechogenicity, well-defined margin and no or dot-lined enhancement (wider-than-tall shapes: 36 vs. 17, χ2=8.511; well-defined margin: 30 vs. 15, χ2=4.523; marked hypoechogenicity: 27 vs. 9, χ2=9.310; no or dot-lined enhancement: 24 vs. 3, χ2=33.369; all P＜0.05). A multivariate analysis demonstrated that wider-than-tall shapes, well-defined margin and marked hypoechogenicity were independent predictors for DCTN (OR values were 5.204, 3.134 and 5.042, P values were 0.003, 0.031, and 0.003, respectively). Among 28 DCTN, 15 showed a decrease in mean maximum diameter (24.3±11.4 mm) with a mean time span of (18.6±10.5) months between the presence and absence of suspicious ultrasound features. Conclusions: Compared with PTC, DCTN shows the ultrasound characteristics of wider-than-tall shapes, well-defined margin, marked hypoechogenicity and no or dot-lined enhancement pattern. Ultrasound follow-up can help to identify spontaneous DCTN.

Long-term rituximab treatment of refractory idiopathic inflammatory myopathy: A report of 3 cases / 北京大学学报(医学版)

Idiopathic inflammatory myopathies are a group of rare but serious diseases. The treatment of refractory idiopathic inflammatory myopathy is always challenging, especially in children. Three cases of refractory idiopathic inflammatory myopathy treated by rituximab were reported and discussed with the review of relevant literature. All were female with on-set age of 8 years and 6 months, 11 years and 7 months, 4 years and 2 months old, respectively. All had acute onset, presenting with progressive and severe muscle weakness. All lost ambulation within 1 or 2 months, with difficult swallowing and low voice. Respiratory distress occurred in case 2 after an attack of asphyxia due to an aspiration of sputum, and ventilator support was required for 1 month. Rashes were detected at the initial stage of the disease in cases 2 and 3. Patient 2 showed facial erythematous papules, spreading to her neck and hands. Patient 3 showed purplish eyelids with peri-orbital swelling, generalized edema involving all her limbs. Creatine kinase (CK) levels were markedly elevated in all the patients, ranging from 6 000 IU/L to 28 819 IU/L. Anti-SRP antibody was identified in cases 1, and anti-NXP2 antibodies were confirmed in cases 2 and 3. MRI of both thighs in all the patients showed profound muscle and fascial edema. Muscle pathology of patient 1 showed prominent fiber variation and endomysial fibrosis, with overexpression of MHC-Ⅰ. While muscle pathology in patients 2 and 3 showed scattered fiber necrosis, regeneration, endomysial edema without inflammatory cell infiltration. All the patients were diagnosed with idiopathic inflammatory myopathy and failed to the initial treatment including adequate glucocorticoids and high-dose immunoglobulin therapy. Other immunosuppressants (methotrexate, cyclophosphamide) were also tried in cases 2 and 3 with poor response. Then all the patients were treated with rituximab combined with glucocorticoids. Patient 1 regained normal strength and discontinued rituximab at the end of her last follow-up (2 years and 7 mouths). Though calcinosis developed during the follow-up period, significant improvement was noticed in cases 2 and 3 (both regained the ability to walk independently) at the end of their last follow-up after 2 years and 8 months, 3 years and 2 months respectively. Long-term rituximab therapy may improve the prognosis of refractory idiopathic inflammatory myopathy, especially with positive anti-SRP and anti-NXP2 antibodies.

Polarization of bone marrow-derived macrophages induced by recombinant Trichinella spiralis cysteine protease inhibitors in vitro / 中国血吸虫病防治杂志

Objective To investigate the regulatory role of recombinant Trichinella spiralis cysteine protease inhibitors (rTs-Cys) in induction of polarization of bone marrow-derived macrophages (BMDMs) in vitro. Methods BMDMs were captured and cultured in conditioned medium for 7 days. Then, mature BMDMs were harvested and assigned into four groups. Cells in Group A (negative control) were given 10 ng/mL IFN-γ combined with 100 ng/mL LPS, cells in Group B (positive control) were treated with IL-4 and IL-10 (at 10 ng/mL both), and cells in Group C (recombinant protein alone) were stimulated with 1 μg/mL rTs-Cys, while cells in Group D (protein co-culture) were simultaneously treated with 1 μg/mL rTs-Cys, 10 ng/mL IFN-γ and 100 ng/mL LPS. Cells and culture supernatant were collected 24 hour post-treatment, and the proportions of F4/80+, CD11b+, CD206+ and CD11c+ cells were detected by flow cytometry. The levels of interleukin IL-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-10 and transforming growth factor-β (TGF-β) in the cell culture supernatant were measured by ELISA and the CD86+ and CD206+ phenotypes were identified by immunofluorescent staining. Results Flow cytometry detected no significant difference in the proportion of F4/80+ CD11b+ CD11c+ cells among the four groups (F = 46.184, P < 0.001), and a lower proportion of F4/80+ CD11b+ CD11c+ cells was seen in groups C and D than in group A (all P values < 0.001). There was a significant difference in the proportion of F4/80+ CD11b+ CD206+ cells among the four groups (F = 11.032, P < 0.001), and a greater proportion of F4/80+ CD11b+ CD206+ cells was seen in groups C and D than in group A (all P values < 0.01). Immunofluorescent staining showed higher CD206+ expression and lower CD86+ expression in groups C and D than in Group A. There were significant differences in the IL-6 and (F = 3.950, P < 0.001) and TNF-α (F = 205.827, P < 0.001) levels in the cell culture supernatants among the four groups, and significantly lower IL-6 and TNF-α levels were measured in groups C and D than in Group A (both P < 0.05). There were significant differences in the IL-10 and (F = 8.274, P < 0.001) and TGF-β (F = 13.559, P < 0.01) levels in the cell culture supernatants among the four groups, and greater IL-10 and TGF-β levels were measured in Group C than in Group A (both P values < 0.01). In addition, the TGF-β level was significantly higher in Group D than in Group A (P < 0.05); however, there was no significant difference in the IL-10 level between groups D and A (P > 0.05). Conclusion rTs-Cys may induce the polarization of BMDMs to antiinflammatory M2 macrophages in vitro and inhibit the activation of M1 macrophages.

Saikosaponin-b2 alleviates CCL4-induced acute liver injury in mice by inhibiting endoplasmic reticulum stress signal pathway / 中国药理学与毒理学杂志

OBJECTIVE To investigate the protective effect of saikosaponin-b2 (SS-b2) on acute liver injury induced by carbon tetrachloride (CCI4) and its inhibition on endoplasmic reticulum stress pathway in mice. METHODS Sixty male BALB/c mice were randomly divided into normal control, model, SS-b2 (5, 10 and 20 mg·kg-1) and silymarin (10 mg·kg-1) groups. Mice were ig given different drugs or saline for 7 d. Two hours after the last administration, mice were IP given 5% CCI4 to induce acute liver injury, except those in normal control group. The activities of glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT) and superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in mouse serum were detected by colorimetric method. Pathological changes in liver tissue were detected by HE staining. The expression levels of protein kinase R-like ER kinase (PERK), phospho-eukaryotic initiation factory 2a (p-elF2α), activating transcrIPtion factor-4(ATF4), glucose regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were detected by immuno-histochemistry and Western blotting. RESULTS Compared with the normal control group, the activities of GPT and GOT and the content of MDA in mouse serum in model group were significantly increased (P<0.05, P<0.01), but the activity of SOD was significantly decreased (P<0.01). Meanwhile, the expression levels of PERK, p-elF2α, ATF4, GRP78 and CHOP in the liver tissue were significantly increased in the model group (P<0.01). Compared with the model group, SS-b2 groups significantly reduced the activity of GPT, GOT and the content of MDA in the serum of acute liver injury mice (P<0.05, P<0.01), but increased the activity of SOD (P<0.01), and the expression levels of endoplasmic reticulum stress pathway proteins mentioned above were significantly reduced (P<0.05, P<0.01). HE staining results showed that different concentrations of SS-b2 could significantly improve the swelling of hepatocytes, the dissolution of nuclei around hepatic lobules, and the arrangement disorder of hepatic cords induced by CCI4 in mice. The cell morphology was obviously improved. CONCLUSION SS-b2 has a significant protective effect on CCL-induced acute liver injury in mice. The mechanism may be related to the inhibition of oxidative stress and down-requlation of the expressions of ERS related protein.

Poly(lactic acid) electrospun fiber membranes carrying gemcitabine hydrochloride inhibit the growth of bone tumor / 中国组织工程研究

BACKGROUND:Gemcitabine hydrochloride is a water-soluble anticancer drug that induces apoptosis in tumor cells, but it has an excessive release in vivo. OBJECTIVE:To evaluate the effect of poly(lactic acid) (PLA) electrospun fiber membranes carrying gemcitabine hydrochloride on the growth of human osteosarcoma cell lines MG-63. METHODS:PLA electrospun fiber members with (experimental) or without (control) gemcitabine hydrochloride were fabricated and characterized. Two kinds of fiber membranes were immersed in low-glucose DMEM medium, and the supernatants were collected in the two groups at 3, 5, 7 days, respectively. Passage 5 human osteosarcoma cell lines MG-63 were inoculated into 96-well plates containing low-glucose DEME with 15％ fetal bovine serum, and divided into seven groups. Groups 1-3 were cultured in the experimental supernatants of 3, 5, 7 culture days, and groups 4-6 were cultured in the control supernatants of 3, 5, 7 culture days, respectively. The remaining group acted as the negative control with no supernatant. Thereafter, cell counting kit-8 was used to detect cell proliferation, and RT-PCR was used to measure expression of Bcl-2 and Bax at 3 days of culture. RESULTS AND CONCLUSION:(1) No obvious particle was found on the smooth and even surface of the fiber members in the experimental and control groups. There was no significant difference in fiber diameter, contact angle and tensile strength between the two kinds of fiber membranes. (2) The results of cell counting kit-8 showed that compared with the negative control group, the supernatant released from the control group had no effect on the MG-63 proliferation at different time points, while the supernatant released from the experimental group could inhibit the MG-63 proliferation at different time points (P<0.05), and the inhibitory effect became more and more obvious with the prolongation of release time. (3) RT-PCR findings showed that compared with the control group, the supernatant released from the experimental group could increase Bax mRNA expression and decrease Bcl-2 mRNA expression at the same time point. To conclude, the PLA electrospun fiber membranes carrying gemcitabine hydrochloride can sustainably inhibit MG-63 proliferation and promote cell apoptosis.

Preparation and biocompatibility of polyethylene glycol hydrogels auto-recruiting transforming growth factor beta1 / 中国组织工程研究

BACKGROUND:Studies have shown that bioactive molecules or polypeptides grafted onto the surface of polyethylene glycol (PEG) hydrogels can improve PEG bioactivities.OBJECTIVE:To manufacture PEG hydrogels capable of auto-recruiting growth factor beta1 (TGF-β1) and to study its biocompatibility. METHODS:Pure PEG hydrogels (group A), PEG hydrogels grafted on a cell adhesion peptide RGD peptides (group B), PEG hydrogels grafted with auto-recruited TGF-β1 peptide sensitive polypeptide HSNGLPL (group C), PEG hydrogels grafted with both RGD and HSNGLPL polypeptides (group D) were prepared. Contract angle of the hydrogel was detected in each group. Human bone mesenchymal stem cells were seeded onto four kinds of hydrogels. After cells attached, scanning electron microscope and LIVE/DEAD staining were done to observe cell-hydrogel compounds. Human bone marrow mesenchymal stem cells were co-cultured with ordinary culture medium (control) or four kinds of hydrogels for 1, 3, 5, 7 days, and the cell proliferation was detected by cell counting kit-8 assay. The four kinds of hydrogels were put into 24-well culture plates with addition of PBS containing TGF-β1, and 1 hour later, immunofluorescence staining was done. RESULTS AND CONCLUSION:(1) The contact angles of groups A and C were larger than those of groups B and D. (2) Under the scanning electron microscope, groups A and C had little cells attached on the hydrogel surface, but there were many cells on the hydrogel surface in groups B and D. (3) LIVE/DEAD staining showed groups A and C had little living cells, and conversely groups B and D had many living cells. (4) The results of cell counting kit-8 demonstrated that as the incubation time went on, cell proliferation activity of five different groups increased with no difference at the same time point. (5) Findings from the immunofluorescence staining showed that groups A and B had very weak fluorescence, while groups C and D had stronger green fluorescence. In conclusion, PEG hydrogels grafted with RGD and HSNGLPL polypeptides can auto-recruit TGF-β1, and have good biocompatibility.

Effect of cystatin from Schistosoma japonicum on DSS-induced ulcerative colitis in mice / 中国血吸虫病防治杂志

Objective To investigate the effect of cysteine protease inhibitor derived from S chistosoma japonicum(SjCys-tatin)on dextran sodium sulfate(DSS)-induced acute ulcerative colitis in mice.Methods Eighteen C57BL/6 mice were ran-domly divided into three groups:a control group treated with PBS(Group A),a DSS-induced-colitis group treated with PBS(Group B),and a DSS-induced-colitis group treated with SjCystatin(Group C).Colitis was induced in mice by giving 3％DSS orally for 7 days.During this period,the mice were daily injected with 10μg of SjCystatin or PBS only as a control intraperitone-ally.The mice were monitored daily for their clinical manifestations and given scores based on disease activity index(DAI).The severity of colonic inflammation was monitored by the macroscopic score and pathological change.The cytokine profile including TNF-α,IL-4,IL-6 and IL-10 in the supernatants of colon homogenate was detected by ELISA.Results Compared with Group A(0.50 ± 0.28),the DAI score increased significantly in Group B(9.30 ± 1.30)(F=86.86,P<0.01),with remarkable path-ological damages seen in colon tissues.and the levels of TNF-α and IL-6 were(321.33±67.01)and(403.58 ±180.51)pg/mL.The DAI score significantly reduced in Group C(6.67±1.57)as compared to Group B(F=86.86,P<0.01),with improve-ments in the macroscopic and microscopic pathology in mouse colon specimens.As compared to Group B,the levels of TNF-α [(188.14 ± 40.14)pg/mL] and IL-6 [(209.71 ± 48.47)pg/mL] significantly decreased(F=17.46 and 9.89,both P<0.01).Con-clusion SjCystatin has a significantly inhibitory effect for alleviating DSS-induced acute ulcerative colitis in C57BL/6 mice.

Training and Demand Analysis of Health Information Management Undergraduate Talents against the Background of "Internet + Medical" / 医学信息学杂志

The paper discusses the training situation of Chinese undergraduate talents majoring in health information management from the aspects including setup of the health information management specialty in higher learning institutions in China,enrolment programs and arrangement of major courses,analyzes demands of hospital informatization on health information talents,and providing reference for the training of more qualified talents of the specialty.

Traditional Chinese medicine fumigation combined with Levofloxacin for type ⅢA prostatitis with the symptoms of damp heat and blood stasis / 中华男科学杂志

Objective@#To investigate the clinical effects of traditional Chinese medicine (TCM) fumigation on type ⅢA prostatitis with the symptoms of damp heat and blood stasis.@*METHODS@#We randomly divided 72 cases of type ⅢA prostatitis with the symptoms of damp heat and blood stasis into an experimental and a control group of equal number, the former treated with TCM fumigation plus oral Levofloxacin while the latter with oral Levofloxacin only. After 4 weeks of treatment, we compared the National Institute of Health Chronic Prostatitis Symptom Index (NIHCPSI) score, TCM symptoms score, maxinum flow rate (Qmax), and average urinary flow rate (Qave) between the two groups of patients.@*RESULTS@#The total effectiveness rate was significantly higher in the experimental than in the control group (91.7% vs 61.1%, P0.05) or in Qave (［10.9 ± 2.4］ vs ［11.1 ± 2.9］ ml/s, P>0.05).@*CONCLUSIONS@#TCM fumigation combined with Levofloxacin is an effective therapy for type ⅢA prostatitis with the symptoms of damp heat and blood stasis, which can significantly improve the symptoms, reduce the NIHCPSI score, and increase the Qmax and Qave of the patient.

Saikosaponins-b suppresses tumor growth and angiogenesis of hepatocellular carcinoma by regulating VEGF/ERK/HIF-1α signal pathway / 中国药理学与毒理学杂志

OBJECTIVE Angiogenesis therapy has attracted interest as a potential treatment for hepatocellular carcinoma (HCC). In this study, we investigated the anti-proliferative activities and anti-angiogenesis effects of saikosaponins (SS)-b on hepatocellular carcinoma (HCC) and its regulation on VEGF/ERK/HIF-1α signal pathway. METHODS H22 hepatoma-bearing mice model and HepG-2 cells were used to study the anti-tumor and anti-angiogenesis effects of SS-b in vivo and in vitro. Pathological change of tumor tissue was observed by HE staining, the microvascular changes were detected by immunohistochemical method. The effects of SS-b on angiogenesis were examined by using the chick embryo chorioallantoic membrane (CAM) model. The effects of SS- b on proliferation, migration and invasion were investigated by MTT assay, scratch wound healing assay and transwell assay inhuman umbilical vein endothelial cell (HUVEC) and HepG2 cells in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase-2/9(MMP-2/9), hypoxia-inducible factor-1α (HIF-1α) expression and the phosphorylation of extracellular regulated kinase(ERK) were analyzed using RT-PCR and Western-blot. RESULTS SS-b effectively inhibited the tumor growth of H22 mice in vivo. The inhibitory rate of tumor was 49.1%, 50.7%, 66.1% in SS-b 5, 10 and 20 mg·kg-1 group respectively. HE staining results showed that SS-b induced tumor necrosis and nuclear dissolution in H22 mice. Moreover, SS-b also reduced the number of microvessels of tumor tissue in H22 mice significantly and suppressed the angiogenesis of CAM induced by b-FGF. SS-b had an obvious inhibitory effect on cell proliferation, migration and invasion of HUVEC cells and HepG-2 cells. These effects were associated with down-regulation of the expression of MMP2/9 and suppression of VEGF/ERK/HIF-1α signaling in H22 mice and Hep-G2 cells. CONCLUSION Our findings showed that SS-b exerts anti-tumor effects by inhibit?ing tumor angiogenesis via regulating VEGF/ERK/HIF-1α signal pathway in vivo and in vitro.

Saikosaponin-b regulates the proliferation and apoptosis of HepG2 cells by targeting the MACC1/c-Met/Akt signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that has been newly identified. It promotes tumor proliferation and invasion via the MET pathway. Our study investigated the effects of Saikosaponin-b(SS-b) on the proliferation and apoptosis of HepG2 cells and its regulation on MACC1/c-Met/Akt signaling pathway. METHODS HepG2 cells were treated with SS-b (10-800 g·L-1) for 48 h in vitro. The CCK-8 assay was used to assess cell proliferation, and cell apoptosis was determined by Hoechst33258 staining, AnnexinⅤ/PI staining and caspase 3 assay. RT-PCR was used to examine the expression of MACC1, c- MET and hepatocyte growth factor (HGF) mRNA. MACC1 protein was detected by Western blot and immunohistochemistry. The protein expressions of p-c-MET, c-MET, p-AKT, AKT, p-BAD, BAD were measured by Western blot. RESULTS SS-b inhibited the growth of HepG2 cells in dose-dependent way and induced cell apoptosis significantly. HepG2 cells showed karyopyknosis, fragmentation and fluorescence highlight in SS-b treatment group. FCM results showed that apoptosis rate of HepG2 cells increased with SS- b concentration. The immunofluores?cence results showed that the MACC1 expression decreased significantly in HepG2 cells treated with SS-b. The expression levels of MACC1, c-MET and HGF mRNA in HepG2 cells were significantly inhibited by SS-b. SS-b also significantly decreased the protein expressions of MACC1, p-c-MET and p-AKT while increased the expression of p-BAD and caspase 3 in HepG2 cells(P<0.05). CONCLUSION SS-b inhibited the proliferation and induced the apoptosis of HepG2 cells by targeting the MACC1/c-Met/Akt signaling pathway.

Longbishu Capsule combined with mesylate doxazosin: an efficacious therapy for benign prostatic hyperplasia / 中华男科学杂志

<p><b>OBJECTIVE</b>To assess the clinical effect and safety of the Chinese medicine Longbishu Capsule combined with mesylate doxazosin in the treatment of benign prostatic hyperplasia (BPH) of the kidney deficiency and blood stagnation type.</p><p><b>METHODS</b>This was a randomized, double-blind, double-simulation control study. We equally assigned 60 men diagnosed with BPH of the kidney deficiency and blood stagnation type to an experimental and a control group, the former treated with mesylate doxazosin plus Longbishu Capsule and the latter with mesylate doxazosin plus placebo. We compared the International Prostate Symptom Score (IPSS), quality of life (QOL), Chinese symptom score (CSS), maximal urinary flow rate (Qmax), and prostate volume between the two groups of patients before and after 6 months of medication.</p><p><b>RESULTS</b>After treatment, there were 5 cured cases, 13 markedly effective cases, 9 effective cases, 1 ineffective case, and 2 eliminated cases in the experimental group, as compared with 2 cured cases, 8 markedly effective cases, 10 effective cases, 7 ineffective cases, and 3 eliminated cases in the control group. The total effectiveness rate was obviously higher in the former (96.4%) than in the latter (74.1%). IPSS, Qmax, and CSS were improved in both of the groups after medication, even more significantly in the experimental than in the control group (IPSS: 15.22 ± 2.98 vs 18.15 ± 5.88, P <0.05; Qmax: [13.56 ± 2.26] ml/s vs [11.78 ± 2.97] ml/s, P <0.05; CSS: 6.18 ± 2.13 vs 9.52 ± 3.15, P <0.05). Because of the difference in the QOL score between the two groups at the baseline (P = 0.038 <0.05), no more comparison was made in this aspect after treatment.</p><p><b>CONCLUSION</b>The combination of Longbishu Capsule with mesylate doxazosin is safe and effective for the treatment of BPH.</p>

Identification of differentially expressed proteins and validation of the changes of N-ethylmaleimide-sensitive factor in rats with focal cerebral ischemia after transection of the cervical sympathetic trunk / 华中科技大学学报（医学）（英德文版）

Stellate ganglion blockade (SGB) protects patients from focal cerebral ischemic injury, and transection of the cervical sympathetic trunk (TCST) in a rat model can mimic SGB in humans. The purpose of this study was to investigate the mechanisms underlying the neuroprotective effects of TCST on neuronal damage in the hippocampus in a rat model of middle cerebral artery occlusion (MCAO) in an attempt to elucidate the neuroprotective effects of SGB. The modified method of Zea Longa was used to establish the permanent MCAO model. Male Wistar rats were randomly divided into three groups: sham-operated group, MCAO group, and TCST group. The animals in TCST group were sacrificed 48 h after TCST which was performed after the establishment of the MCAO model. Proteins were extracted from the ipsilateral hippocampus and analyzed by two-dimensional difference gel electrophoresis (2D-DIGE) and peptide mass fingerprinting (PMF). The levels of N-ethylmaleimide-sensitive factor (NSF) were measured as well. The results showed that 11 types of proteins were identified by 2D-DIGE. The expressions of eight proteins were changed both in the sham-operated and TCST groups, and the expressions of the other three proteins were changed in all three groups. Moreover, the expression of NSF was higher in the TCST group than in the MCAO group but lower in the MCAO group than in sham-operated group. The ratio of NSF expression between the MCAO group and shamoperated group was -1.37 (P<0.05), whereas that between the TCST group and MCAO group was 1.35 (P<0.05). Our results imply that TCST increases the expression of NSF in the hippocampus of adult rats with focal cerebral ischemia, which may contribute to the protection of the injured brain. Our study provides a theoretical basis for the therapeutic application of SGB to patients with permanent cerebral ischemia.

Transurethral bipolar plasmakinetic enucleation and resection versus transurethral bipolar plasmakinetic resection of the prostate for BPH: a randomized controlled trial on the incidence of postoperative urinary incontinence / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the incidence rates of postoperative urinary incontinence between transurethral bipolar plasmakinetic enucleation and resection of the prostate (PKERP) and transurethral bipolar plasmakinetic resection of the prostate (PKRP), and provide evidence for the clinical application of PKERP.</p><p><b>METHODS</b>Totally, 180 BPH patients were equally and randomly assigned to undergo PKERP and PKRP, respectively. We measured the urinary incontinence of the patients by pad test at 24 hours after extubation and every week after surgery for 4 weeks. Meanwhile, we recorded and compared the PSA level, prostate volume, Qmax, residual urine, IPSS, QOL, and the results of pad test between the two groups before and after surgery.</p><p><b>RESULTS</b>The incidence rates of urinary incontinence in the PKERP and PKRP groups were 35.56% and 18.89% (P < 0.01) at 24 hours after extubation, 20.00% and 7.78% at 1 week after surgery (P < 0.05), and 3.33% and 2.22% at 2 weeks. There was no significant difference in the severity of urinary incontinence between the two groups at any time point (P > 0.05). No permanent urinary incontinence was observed in either group.</p><p><b>CONCLUSION</b>Compared with PKRP, PKERP has a higher incidence rate of short-term urinary incontinence in the treatment of BPH, but not that of genuine incontinence, with similar severity and recovery time.</p>

Identification of differentially expressed proteins and validation of the changes of N-ethylmaleimide-sensitive factor in rats with focal cerebral ischemia after transection of the cervical sympathetic trunk / 华中科技大学学报（医学）（英德文版）

Stellate ganglion blockade (SGB) protects patients from focal cerebral ischemic injury, and transection of the cervical sympathetic trunk (TCST) in a rat model can mimic SGB in humans. The purpose of this study was to investigate the mechanisms underlying the neuroprotective effects of TCST on neuronal damage in the hippocampus in a rat model of middle cerebral artery occlusion (MCAO) in an attempt to elucidate the neuroprotective effects of SGB. The modified method of Zea Longa was used to establish the permanent MCAO model. Male Wistar rats were randomly divided into three groups: sham-operated group, MCAO group, and TCST group. The animals in TCST group were sacrificed 48 h after TCST which was performed after the establishment of the MCAO model. Proteins were extracted from the ipsilateral hippocampus and analyzed by two-dimensional difference gel electrophoresis (2D-DIGE) and peptide mass fingerprinting (PMF). The levels of N-ethylmaleimide-sensitive factor (NSF) were measured as well. The results showed that 11 types of proteins were identified by 2D-DIGE. The expressions of eight proteins were changed both in the sham-operated and TCST groups, and the expressions of the other three proteins were changed in all three groups. Moreover, the expression of NSF was higher in the TCST group than in the MCAO group but lower in the MCAO group than in sham-operated group. The ratio of NSF expression between the MCAO group and shamoperated group was -1.37 (P<0.05), whereas that between the TCST group and MCAO group was 1.35 (P<0.05). Our results imply that TCST increases the expression of NSF in the hippocampus of adult rats with focal cerebral ischemia, which may contribute to the protection of the injured brain. Our study provides a theoretical basis for the therapeutic application of SGB to patients with permanent cerebral ischemia.

Phenotype/genotype analysis of 4 cases of LMNA related congenital muscular dystrophy with inflammatory changes / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics,muscle pathological features and pathogenic gene mutation in 4 cases with LMNA-related congenital muscular dystrophy (L-CMD).Methods Clinical data of the probands and the parents were collected.Skeletal muscle specimens were biopsied from the probands for pathological analysis.Genomic DNA and RNA were extracted from peripheral blood leukocytes,and PCR,reverse transcription(RT)-PCR and DNA direct sequencing were employed to analyze the LMNA gene to determine the gene mutation and confirm the pathogenicity.Results Four patients had symptoms from fetal period to several months after birth.They presented with motor retardation,muscle weakness with prominent the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,with mild to moderate elevation of CK level.The muscle biopsies showed muscular dystrophic and with inflammatory changes,and the abnormal nuclear morphology was observed with transmission electron microscopy.Genetic analysis of them detected 4 dominant de novo mutations.Three of them had unreported pathogenic mutations.The same sites of the LMNA gene were wild type in their parents.Conclusions Four cases of L-CMD are genetically identified.Genetic counseling of the family can be possible.The patients should be considered LMNA gene mutation of they present themselves with muscle weakness with the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,mild to moderate elevation of CK level,and if the biopsies show muscular dystrophic changes but also with inflammatory changes should be considered LMNA gene mutation.Genetic analysis is the most reliable method for diagnosing L-CMD.

Stevens-Johnson syndrome induced by sodium valproate:a case report and literatures review / 中华实用儿科临床杂志

Objective To explore the clinical diagnosis and treatment of Stevens-Johnson syndrome induced by sodium valproate.Methods The clinical manifestations,investigation findings and treatment of 1 patient with Stevens-Johnson syndrome induced by sodium valproate,and the related literatures were reviewed.Results The patient was a 3.5-year-old girl who was initially diagnosed with epilepsy.After 14 days of monotherapy with oral sodium valproate,an erythematous rash appeared on the face,and gradually spread to her trunk and limbs with severe itching.The rash rapidly got worsened,and developed flakiness and herpetic lesions that involved swelling and ulceration of the lip mucosa.Two days after the rash appeared,she became febrile with body temperature up to 39.5 ℃.Lymphadenectasis and a palpable 2 cm liver edge were found on examination.Her glutamate pyruvate transaminase was 139 IU/L and the concentration of blood ammonia was 108 μmol/L.The administration of sodium valproate was discontinued imme-diately and methylprednisolone intravenous pulse therapy [15 mg/(kg · d)] was administered.Two days later,she was afebrile and the rash gradually resolved within 7 days of treatment.Her liver function also returned to normal.Conclusions A high degree of vigilance against sodium valproate-induced Stevens-Johnson syndrome was crucial to the early clinical diagnosis and successful treatment of this patient.The prompt discontinuation of the causative medication and sufficient corticosteroid hormone therapy can achieve a good outcome.

A family with autosomal dominant Emery-Dreifuss muscular dystrophy and literature review / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics,muscle pathological features and pathogenic gene mutation of a family with autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD).Methods Clinical data of the proband and her family members,a Chinese family of AD-EDMD,were collected.Skeletal muscle specimens were collected from the proband for pathological analysis.Genomic DNA from the proband and her parents was extracted using standard procedures from the peripheral blood leukocytes.PCR and DNA direct sequencing were employed to analyze all of the 12 exons of the LMNA gene to determine the gene mutation,and the case was summarized along with related literature review.Results The proband,female,4 years and 5 months old now,presented with muscle weakness during her early childhood,the proximally was more prominent,mild pectus excavatum.Her CK level was elevated,her electromyogram showed myogenic injuries,the muscle biopsy showed myopathy changes.Her father had the same symptom,with disease progressed,showed elbow contractures in early stage,stiff neck,tight achilles tendon,slowly progressive muscle weakness of the limbs,sinus bradycardia.A heterozygous missense mutation c.1580G ＞ C (p.Arg527Pro) was identified in exon 9 of the LMNA gene in the proband and her father,but not in her mother.This heterozygous missense mutation had been reported as a pathogenic gene mutation.Conclusions The patient who has elbow contractures in early stage,limited neck flexion,spine stiffness,muscle weakness with the proximal upper limbs and distal lower limbs,and arrhythmia,should have an analysis of the LMNA gene.It's important for the early diagnosis of EDMD,assessment of the prognosis,timely and effectively monitoring the changes of arrhythmia,then taking interventions to improve the quality of life and prolong life.So genetic analysis is most reliable method to diagnose EDMD.

Clinical, pathological and molecular biological characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To delineate the characteristics of the clinical manifestation, pathology of skeletal muscle and gene mutations of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) in children.</p><p><b>METHOD</b>The clinical manifestation, laboratorial data, brain images, muscle pathology and mitochondrial gene mutations were analyzed in 24 patients with MELAS who were diagnosed in Department of Pediatrics, Peking University First Hospital. Their prognosis was evaluated by following up.</p><p><b>RESULT</b>Symptoms of central nervous system such as stroke-like episodes, vomiting, convulsion and headache were present in all the 24 cases. Nine cases had the symptoms of myopathy. Twenty cases had developmental delay. Short stature, being thin and hairy was very common in these cases. Serum lactate level increased in all the cases, pyruvate increased in 17 cases. Elevated CSF lactate was found in 2 cases. Magnetic resonance imaging (MRI) was performed on 24 cases, out of them 23 were abnormal. The lesions mainly involved cerebral lobes. Occipital lobe was the most common site of lesions. Computed tomography (CT) was performed on 13 cases, low density lesions were present in 10 cases, basal ganglia calcifications in 5 cases. Muscle biopsy was performed on 8 cases, ragged-red fibers (RRF) were found in 4/8 cases, and abnormal accumulation of mitochondria were found in 3/8 cases. The mtDNA gene mutational analysis showed A3243G mutation in these patients. The mutation rates varied from 11.6% to 75.0%. The same mutation were found in 4/5 mothers who had the genetic tests, and the mutation rates of the mothers varied from 15.0% to 23.6%. The clinical information of 11 cases was available through recent following up. Three cases died, the others had some degrees of mental retardation.</p><p><b>CONCLUSION</b>Children with MELAS had various clinical manifestations. Central nervous system and skeletal muscle were usually involved. Short stature and hypertrichosis were common signs. The prognosis of this disease was disappointing. mtDNA A3243G was the most common mutation in MELAS. Fully understanding the characteristics of its clinical manifestation, laboratory tests, brain image, muscle pathology and molecular features can be helpful to the early diagnosis and treatment.</p>