Objective To report clinical symptoms of a Chinese pedigree of familial paramyotonia congenital (PMC) with progressive myopathy (PM), and investigate the mutations of hot spots in the adult skeletal muscle sodium channel α-subunit (SCN4A). Methods The medical history and clinical phenotype of the patients from this large family with PMC were collected. Insertional and spontaneous activity were recorded by routine electromyograph (EMG), and the exercise test (ET) and cool water test were also performed on some patients during episodes. The mutations of SCN4A were screened by PCR-SSCP and DNA sequencing in affected and unaffected members. Results The family is a four-generation kindred with 15 members affected by severe, homogeneous paralysis periodiea paramyotoniea pheuotype. The onset was early, and almost all patients developed severe progressive myopathy by middle age. Routine EMG shows myotonia discharge in all affected subjects. The compound remarkably motor action potential (CMAP) decreased more than 40% after ET with greater decreases in cool water test than in ET. The mutation screening study revealed a missense mutation (Met1592Val) in SCN4A in patients. Conclusions Autosomal dominant inheritance pattern with complete penetrance was observed in this family. The phenotype is in accord with that reported in other ethnic populations with more severe symptoms. The ET and cool water tests may be used as an easy and reliable diagnostic method. Our research supports that periodic paralysis and paramyotonia can be caused by the same mutation in SCN4A. Mutation Met1592Val is a hotspot for mutation screening in patients with PMC accompanied by PM in the Chinese population.

Objective To investigate the influence of different doses and courses of cigarette smoking on the expression of ICAM-1 mRNA, ICAM-1 in rats' cerebral vascular endothelial cells and volumes of cerebral infartion.Methods 105 male Wistar rats(weight 210～220 g) were randomly grouped into long-term massive(20 cigarettes/d,75 d), short-term massive(20 cigarettes/d,30 d), long-term trifle (8 cigarettes/d, 75 d), anti-smoking(20 cigarettes/d, 30 d, denying 45 d)and normal control(no smoking). In situ hybridization, immunohistochemistry were used to determine the expression of ICAM-1 mRNA, ICAM-1 in rat's cerebral vascular endothelial cells (VECs).The VEC's structures were observed by electronic microscope. Left middle cerebral artery occlusion model was established and pathologic image analyzing system were used to determine the ratio of the volume of infarction in hemisphere of the same side. Results On contrast to normal controls, the expression of ICAM-1mRNA, ICAM-1 and the volume of infarction were increased in smoking(P

rse effect when compared with tibolone.

Objective To study the desired therapeutic effect of vaginoplasty using sigmoid colon or peritoneum for entire vaginal atre-sia.Methods From May 2015 to October 2015,8 patients with complete vaginal atresia in our hospital performed vaginoplasty using sigmoid colon or peritoneum successfully.The operation methods,prognosis and therapeutic effect and quality of sexual life of two groups were com-pared and analyzed to investigate a perfect operative method and ideal nursing.Results Laparoscopic vaginoplasty using the peritoneum compared with that using sigmoid colon has advantages of shorter time of operation,less bleeding,less trauma and quicker recovery.However, artificial vagina using sigmoid colon was much more similar to a natural vagina in morphological and physiological characteristics,merely ac-companied by excessive mucus discharge during the postoperative period.At lower risk of vaginal adhesion and stenosis,laparoscopically as-sisted vaginoplasty using sigmoid colon graft also puts high technical requirements.Two patients normally developed uterus menstruate regular-ly.Four patients without uterus and 2 patients with rudimentary uterus experienced good sexual intercourse after vaginoplasty.Conclusion Patients with complete colpatresia who have normal womb should creat a patent and functional vagina until adolescence to restore its physio-logical and reproductive function.Anatomical reconstructive treatment of vaginal agenesis for patients with absent or hypoplastic uterus can be postponed till the late teens or in the adult.Both laparoscopic sigmoid vaginoplasty and peritoneal vaginoplasty achieve a minimal-invasive, cosmetic,natural lubricous, smooth artificial vagina for patient’ s sex life satisfactory.

Objective To investigate the differential expression levels and significance of regulatory T cell (Treg) and T helper 17 (Th17) related immunologic factors in peripheral blood of arsenic-exposed rats.Methods Thirty-two Wistar rats were numbered by weight,randomly divided into four groups [control,low (1.25 ml/kg),medium (2.50 ml/kg),and high (5.00 ml/kg)],8 rats per group.Rats in control group were given oral gavage of deionized water,and low,medium and high arsenic exposed groups were given oral gavage doses of 2.00 g/L sodium arsenite (NaAsO2) according to their body weight for 6 days every week.After 4 months,the urine and peripheral blood samples of rats were collected,urinary arsenic (uAs) was detected by inductively coupled plasma-mass spectrometry (ICP-MS),the results were shown in [median (minimum and maximum)],uAs was corrected by urinary creatinine (uCr),the unit was μg/g Cr;enzyme-linked immune-sorbent assay (ELISA) was applied to detect the levels of Treg,Th17,T lymphocytes activation related immunologic factors [interleukin-10 (IL-10),transforming growth factor beta1 (TGF-31),IL-17,IL-6,IL-2],the results were shown in (x) ± s.Results The uAs of the rats was compared between control,low,medium,and high arsenic exposed groups [7.50 (3.16-9.81),72.34 (62.34-106.63),209.15 (154.41-232.20),369.73 (289.50-516.55) μg/g Cr],the differences were statistically significant (F =337.55,P ＜ 0.05).IL-10 [(85.03 ± 7.11),(93.96 ± 8.14),(97.48 ± 6.23),(93.47 ± 4.41) ng/L],TGF-β1 [(72.88 ± 2.96),(81.45 ± 8.15),(86.08 ± 7.55),(90.29 ± 5.35) ng/L],IL-17 [(18.15 ± 3.66),(25.54 ± 5.59),(31.48 ± 5.74),(37.25 ± 7.36) ng/L],IL-6 [(83.68 ± 8.48),(85.14 ± 7.11),(89.78 ± 5.36),(93.48 ± 5.77) ng/L],and IL-2 [(80.65 ± 6.90),(73.86 ± 8.00),(69.93 ± 7.77),(62.06 ± 9.82) ng/L] of the rats were compared between control,low,medium,and high arsenic exposed groups,the differences were statistically significant (F =5.094,11.054,16.249,3.474,5.119,all P ＜ 0.05).There were positive correlations between uAs and TGF-β1,IL-17 concentration (r =0.723,0.605,all P ＜ 0.01),while IL-2 showed a negative correlation (r =-0.484,P ＜ 0.05).Concltsion Arsenic exposure could affect the secretion of Treg and Th17 related immunologic factors,so as to the imbalance of anti-inflammatory and pro-inflammatory,which may play a role in the formation and development of arsenic-related immune injury.

Objective To evaluate the cumulative irritative effect of topical retinoic acid preparations on normal skin.Methods A randomlized,doubled blind,placebo-controlled clinical trial was carried out with7groups for6tested preparations.All subjects were patch tested with each preparation for24hours on Monday to Thursday,and for72hours on Friday.The patch tests were performed for3consecutive weeks.Results The minimal cumulative irritative effects were found in Group G treated with0.1%adapalene gel,with a cumulative irritative index of0.09?0.11in20days.The cumulative irritative index was significantly lower in Group G than that in Group B treated with0.1%retinoic acid(Diweishuang誖)(0.59?0.24),or in0.025%retinoic acid(Diweishuang誖)(0.41?0.22),or in0.05%retinoic acid(VITAMIN誖Cream)(0.25?0.22).Conclusion Adapalene,the third generation of retinoic acid,is characterized by lower irritative ef-fects in comparison to the first generation of topical retinoic acid agents.

OBJECTIVETo investigate the effects of two different dosages of conjugated equine estrogen (CEE) on preventing bone loss and relieving the symptoms of menopausal syndrome in women at an early stage of menopause.

METHODSA total of 236 postmenopausal women were randomly allocated to one of the following groups: Group A: 0.625 mg CEE + 2 mg medroxyprogesterone acetate (MPA) + 1 tab Caltrate-D per day; Group B: 0.3 mg CEE + 2 mg MPA + 1 tab Caltrate-D per day; Group C: 1 tab Caltrate-D per day as the control group. The study was continued for 2 years.The following parameters were monitored: (1) L2-4 bone mineral density (BMD) (measured with dual energy X-ray absorptiometry (DEX)), (2) menopausal syndrome improvement (assessed by comparing Kupperman scores), (3) vaginal bleeding rate, and the thickness of the endometrium and breast in each group.

RESULTSOverall, 213 cases (90%) completed the 1-year study and 176 cases (75%) completed the 2-year study. The percentage changes in L2-4 BMD at the 12th and 24th month in Group A were +2.3% and +3.7%, respectively, with the posttreatment values being significantly higher than pretreatment values (P < 0.001). The percentage changes were +2.7% at 12th month (P < 0.05) and +0.7% at 24th month (P > 0.05) in Group B. And that of Group C were -0.4% at 12th month and -1.6% at 24th month (P > 0.05). L2-4 BMD in both Group A and B was significantly higher than that in Group C at 12th and 24th month (A vs C, P < 0.001; B vs C, P < 0.05). Kupperman Scores were significantly reduced after 1, 3, 6, 12 and 24 months in all 3 groups when compared with baseline (P < 0.001). Scores in Group A and Group B were significantly lower than that in Group C (P < 0.001). However, the vaginal bleeding rates in Group A were significantly higher than that in Group B or in Group C. There was no atypical hyperplasia of endometrium in the 3 groups by the end of the study. One patient in Group A developed superficial thrombophlebitis by the end of 12th month.

CONCLUSIONContinuous combination of CEE and MPA is effective in preventing bone loss and relieving the symptoms of menopausal syndrome in women at an early stage of menopause. The vaginal bleeding rates in the Group treated with 0.625 mg/d CEE were significantly higher than those treated with 0.3 mg/d CEE.

Alkaline Phosphatase ; blood ; Bone Density ; drug effects ; Endometrium ; pathology ; Estrogens, Conjugated (USP) ; administration & dosage ; Female ; Hormone Replacement Therapy ; adverse effects ; methods ; Humans ; Menopause ; Middle Aged ; Progestins ; administration & dosage ; Uterine Hemorrhage ; epidemiology

The corona virus disease 2019 (COVID-19) has recently become pandemic and is still spreading. Many severe or critical COVID-19 cases meet the diagnostic criteria of sepsis and septic shock in the clinical manifestations. It is important to study the pathogenesis and treatment strategy of COVID-19 for the disease prevention and control. This article reviews the clinical features and treatment progress of COVID-19 viral sepsis.

OBJECTIVETo determine the effects of raloxifene hydrochloride (RLX) on bone mineral density (BMD), bone metabolism markers and serum lipids in healthy postmenopausal women in Beijing.

METHODSA multicenter, randomized, double-blind, placebo-controlled study was conducted in a total of 204 healthy postmenopausal women (age 59.5 +/- 5.0 years and weight 62.8 +/- 8.7 kg) treated with either RLX 60 mg (n = 102) or placebo (n = 102) daily for 12 months. BMD, serum lipids, and bone markers were measured before and after drug administration.

RESULTSCompared with placebo, RLX produced a significant increase in both total lumbar spine and total hip BMD. For the lumbar spine, percentage increase in total BMD was 2.3% with RLX compared with a decrease of 0.1% with placebo (P < 0.001). Corresponding values for total hip BMD were a 2.5% increase for RLX and a 1.1% increase for placebo (P = 0.011). For biochemical markers of bone metabolism, serum osteocalcin and C-telopeptide, percentage decreases were 27.65% and 24.02% in RLX-treated subjects. Corresponding values in placebo were a 10.64% decrease and a 15.75% increase (RLX compared with placebo, both P < 0.001). For total cholesterol and low-density lipoprotein cholesterol levels, percentage decreases were 6.44% and 34.58% in the RLX-treated group. Corresponding values in placebo-treated patients were a 1.44% increase and a 19.07% decrease (RLX compared with placebo, both P < 0.001). No differences were found for high-density lipoprotein cholesterol or triglyceride levels between the two groups. Only 5 subjects discontinued early owing to an adverse event (3 in the RLX group and 2 in the placebo group).

CONCLUSIONSThis study confirms that RLX exerts positive effects on the skeleton, increasing BMD and decreasing biochemical markers of bone metabolism, and has a positive effect on the overall serum lipid profile in postmenopausal women in China.

Aged ; Biomarkers ; blood ; Bone Density ; drug effects ; Bone and Bones ; metabolism ; China ; Estrogen Antagonists ; pharmacology ; Female ; Humans ; Lipids ; blood ; Middle Aged ; Postmenopause ; physiology ; Raloxifene Hydrochloride ; pharmacology ; Selective Estrogen Receptor Modulators ; pharmacology

Objective To investigate the expression of transcription factor forkhead/winged helix transcription factor 3 (Foxp3),immune factor transforming growth factor-beta 1 (TGF-β1),and T-lymphocyte activation related factor interleukin-2 (IL-2) in peripheral blood of patients with coal-burning arsenic poisoning,and to analyze the effects of arsenic exposure on immune function.Methods A case-control study was conducted to investigate 149 cases [94 males and 55 females,(50.69 ± 6.14) years old] of arsenic poisoning in Yuzhang coalburning arsenic poisoning area,southwestern Guizhou Province,and the cases were diagnosed based on the "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015) and confirmed by clinical review.According to skin damage,the patients were divided into mild arsenic poisoning group (39 cases),moderate arsenic poisoning group (54 cases) and severe arsenic poisoning group (56 cases);and 41 cases [12 males and 29 females,(45.76 ± 7.88) years old] of non-arsenic exposed residents from 12 km of Yuzhang coal-burning area were selected as control group.Morning urine and peripheral blood samples were collected with informed consent.Urine arsenic content was measured by inductively coupled plasma mass spectrometry (ICP-MS).Urine arsenic was corrected by creatinine (Cr).Detection of regulatory T cell (Treg)-specific transcription factor Foxp3 gene expression in human peripheral blood was done by real-time fluorescence quantitative PCR,and the levels of Treg-related immune factor TGF-β1 and IL-2 in serum were detected by enzyme linked immunosorbent assay (ELISA).Results The urinary arsenic contents [median (quartile):29.13 (19.75-54.50),31.81 (17.52-53.31),30.51 (18.35-45.76) μg/g Cr] in each arsenic poisoning group were higher than that in the control group [21.62 (17.65-28.44) μg/g Cr,P ＜ 0.05].The expression levels of Foxp3 mRNA in peripheral blood of each arsenic poisoning group [median (quartile):0.58 (0.17-1.27),0.32 (0.17-0.61),0.33 (0.13-0.62)] were significantly lower than that in the control group [0.87 (0.64-1.50),P ＜ 0.05];compared with mild arsenic poisoning group,the expression of Foxp3 mRNA in peripheral blood of moderate and severe arsenic poisoning groups decreased (P ＜ 0.05).The contents of serum TGF-β1 [(13.14 ± 5.19),(12.85 ± 5.51),(12.78 ± 4.95) μg/L] in each arsenic poisoning group were significantly higher than that in the control group [(3.90 ± 1.53) μg/L,P ＜ 0.05].The levels of IL-2 in serum of each arsenic poisoning group [(9.85 ± 5.38),(11.64 ± 6.40),(12.27 ± 6.19) ng/L] were lower than that in the control group [(34.30 ± 4.84) ng/L,P ＜ 0.05];the serum level of IL-2 in severe arsenic poisoning group was higher than that in mild arsenic poisoning group (P ＜ 0.05).Conclusions Arsenic exposure can cause abnormal changes of Treg-specific transcription factor Foxp3 and related immune factors TGF-β1 and IL-2 in peripheral blood of patients.It is suggested that Treg dysfunction may be related to arsenic poisoning.