Objective To explore the diagnosis of clinically suspicious von Willebrand disease(vWD)in a family and its pathogene-sis.Methods The pedigree information and the biological specimen were collected from the clinically suspected VWD patient and her family members(4 persons in total)in Peking University First Hospital.The levels of platelet count(PLT),activated partial thrombo-plastin time(APTT),vWF antigen(vWF:Ag),vWF activity(vWF:Ac)and FⅧ activity(FⅧ:C)were detected,and vWF risto-cetin cofactor(vWF:RCo)assay,ristocetin-induced platelet aggregation assay(RIPA)and vWF collagen binding(vWF:CB)assay were performed for phenotype diagnosis.The peripheral blood genomic DNAs were extracted from the proband and her family members to perform whole-exome sequencing for identifying the mutation of vWF gene,The mutation site was analyzed by using bioinformation tools to explore the pathogenesis of the proband.Results The APTT of proband(m 1)was slightly prolonged and her vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were significantly decreased.There was no obvious aggregation in RIPA assay(1.0 mg/mL and 1.25 mg/mL).In her father(Ⅱ3),APTT,FⅧ:C,vWF:Ag,vWF:Ac and vWF:CB were normal,but vWF:RCo was slightly decreased.In her mother(Ⅱ4),APTT,FⅧ:C,vWF:Ag,vWF:RCo and vWF:CB were all normal,but vWF:Ac significantly decreased.In her brother(Ⅲ2),APTT and FⅧ:C were normal,but vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were reduced to varying degrees.In all the family members(father,mother and brpther),no apparent aggregation in RIPA(1.0 mg/mL)was shown.Genetic analysis showed that the proband(Ⅲ1)carried a compound heterozygous mutation of vWF gene c.7288-9T＞G and c.1117C＞T,her father(Ⅱ3)carried vWF gene c.7288-9T＞G heterozygous mutation,and vWF gene c.1117C＞T heterozygous mutation was presented in both mother(Ⅱ4)and brother(Ⅲ2).Conclusion According to the results of laboratory tests,the proband was diagnosed as type 2A vWD.The hetero-zygous mutation in vWF gene c.1117C＞T and c.7288-9T＞G may be the molecular mechanism leading to type 2A vWD in the proband.

Objective:To evaluate the association between long-term exposure to ambient ozone (O 3) and sperm quality. Methods:From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O 3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O 3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals ( CIs) for all sperm parameters associated with 10 μg/m 3 increases in O 3. The effects of individual characteristics on the association between O 3 and sperm quality were evaluated by stratified analysis. Results:The average O 3 concentration in the year before semen collection was (107.09±7.50) μg/m 3. Each 10 μg/m 3 increase in O 3 was associated with declined sperm concentration (-3.12%, 95% CI:-4.55%, -1.67%), total sperm count (-5.21%, 95% CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95% CI:-2.37%, -0.61%), progressive motility (-2.53%, 95% CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95% CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95% CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O 3 on sperm quality, but the difference was not statistically significant ( P>0.05). Conclusion:Long-term exposure to O 3 in Shandong Province is associated with a decrease in sperm quality.

Objective:To evaluate the association between long-term exposure to ambient ozone (O 3) and sperm quality. Methods:From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O 3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O 3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals ( CIs) for all sperm parameters associated with 10 μg/m 3 increases in O 3. The effects of individual characteristics on the association between O 3 and sperm quality were evaluated by stratified analysis. Results:The average O 3 concentration in the year before semen collection was (107.09±7.50) μg/m 3. Each 10 μg/m 3 increase in O 3 was associated with declined sperm concentration (-3.12%, 95% CI:-4.55%, -1.67%), total sperm count (-5.21%, 95% CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95% CI:-2.37%, -0.61%), progressive motility (-2.53%, 95% CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95% CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95% CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O 3 on sperm quality, but the difference was not statistically significant ( P>0.05). Conclusion:Long-term exposure to O 3 in Shandong Province is associated with a decrease in sperm quality.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Objective To investigate the effect of transcranial direct current stimulation(tDCS)in the left posterior sylvia temporal-parietal association area on language function in patients with post-stroke conductive aphasia.Methods The post-stroke aphasia patients admitted to the Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University were prospectively included from June 2021 to April 2024.A self-cross randomized controlled trial was performed in this study.The patients enrolled were assessed as conductive aphasia by Western aphasia test kit diagnostic criteria.Twelve patients with post-stroke conductive aphasia were completely randomly divided into group A(treatment sequence:stage A—washout period—stage B)and group B(treatment sequence:stage B—washout period—stage A),with 6 cases in each group.Stage A performed true tDCS therapy combined with speech and language training,and stage B performed sham tDCS therapy combined with speech and language training.During washout period,only speech and language training was performed,and each stage was trained for 5 days.The tDCS anode is the stimulation electrode and is placed at the stimulation target.The cathode is the reference electrode and is placed on the right shoulder.The intensity of tDCS was 1.4 mA,the true stimulation was 20 min/time,and the sham stimulation stopped automatically after only 30 s/time,both twice/d,and a total of 10 times treatment were performed.Speech and language training was performed 30 min/time,2 times/d,a total of 10 times treatment.The function of rehearsal and picture naming(training item and non-training item)were examined before and after treatment of stage A and B immediately,and the difference of function scores of rehearsal and picture naming(training item and non-training item)before and after treatment of stage A and B were compared.Results(1)There were no significant differences in gender,age,course of disease and educational level between group A and group B(all P＞0.05).(2)Before and after washout period,there were no statistical significance in functional scores of rehearsal and picture naming(training items and non-training items)in both group A and group B(all P＞0.05).(3)There were no significant differences in functional scores of rehearsal and picture naming(training items and non-training items)between group A and group B before and after washout treatment(all P＞0.05).(4)Compared with the difference before and after treatment of stage B,the function scores difference before and after treatment of stage A in rehearsal function,picture naming(training item)and picture naming(non-training item)were higher([6.9±1.4]scores vs.[2.2±1.0]scores,t=9.604;[6.2±1.2]scores vs.[1.8±1.1]scores,t=9.277;[6.5±1.0]scores vs.[1.5±1.0]scores,t=12.247;all P＜0.01).Conclusions Preliminary analysis suggested that tDCS intervention in the brain tissue of the temporoparietal association area of the left posterior lateral cleft may help improve the rehearsal and picture naming(training and non-training items)ability in conductive aphasia patients after stroke.The sample size of this study is small,and the results need to be further explored.

Objective    To compare the clinical outcomes of transcatheter aortic valve implantation (TAVI) in oncology and non-oncology patients with severe aortic stenosis (AS). Methods    A computer-based search in PubMed, The Cochrane Library, EMbase, CBM, CNKI and Wanfang databases from their date of inception to December 2021 was performed, together with reference screening, to identify eligible clinical trials. Two investigators screened the articles, extracted data, and evaluated quality independently. RevMan 5.3 and Stata 12.0 softwares were used for meta-analysis. Results    The selected 8 cohort studies contained 57 988 patients, including 12 335 cancer patients and 45 653 non-cancer patients. The results of meta-analysis showed that in patients with cancer, the 30-day mortality [OR=0.74, 95%CI (0.65, 0.84), I2=0%, P<0.000 01], stroke [OR=0.87, 95%CI (0.76, 0.99), I2=0%, P=0.04] and acute kidney injury [OR=0.81, 95%CI (0.76, 0.85), I2=49%, P<0.000 01] were lower than those in patients without cancer. The 1-year mortality [OR=1.46, 95%CI (1.15, 1.86), I2=62%, P=0.002] and late mortality [OR=1.51, 95%CI (1.24, 1.85), I2=61%, P<0.000 1] were higher in patients with cancer. Conclusion    It is effective and safe in cancer patients with severe AS undergoing TAVI. However, compared with patients without cancer, it is still high in long-term mortality, and further study of the role of TAVI in cancer patients with AS is necessary.

Objective:To evaluate the safety of two inactivated COVID-19 vaccines in a large-scale emergency use.Methods:Based on the "Vaccination Information Collection System", the incidence data of adverse reactions in the population vaccinated with the inactivated COVID-19 vaccines developed by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd, respectively, in emergency use were collected, and the relevant information were analyzed with descriptive epidemiological and statistical methods.Results:By December 1, 2020, the vaccination information of 519 543 individuals had been collected. The overall incidence rate of adverse reactions was 1.06%, the incidence rate of systemic adverse reactions was 0.69% and the incidence rate of local adverse reactions was 0.37%. The main systemic adverse reactions included fatigue, headache, fever, cough and loss of appetite with the incidence rates of 0.21%, 0.14%, 0.06%, 0.05% and 0.05%, respectively; the main local adverse reactions were injection site pain and injection site swelling with the incidence rates of 0.24% and 0.05%, respectively.Conclusion:The two inactivated COVID-19 vaccines by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd showed that in the large-scale emergency use, the incidence rate of general reactions was low and no serious adverse reactions were observed after the vaccinations, demonstrating that the vaccines have good safety.

BACKGROUND AND PURPOSE: Tafamidis functions to delay the loss of function in transthyretin familial amyloid polyneuropathy (TTR-FAP), which is a rare inherited amyloidosis with progressive sensorimotor and autonomic polyneuropathy. This systematic literature review and meta-analysis evaluated the efficacy and safety of tafamidis in TTR-FAP patients, with the aim of improving the evidence-based medical evidence of this treatment option for TTP-FAP. METHODS: A systematic search of the English-language literature in five databases was performed through to May 31, 2018 by two reviewers who independently extracted data and assessed the risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS: The meta-analysis identified six relevant studies. The tafamidis group showed smaller changes from baseline in the Neuropathy Impairment Score–Lower Limbs [mean difference (MD)=−3.01, 95% confidence interval (CI)=−3.26 to −2.75, p < 0.001] and the Norfolk Quality of Life-Diabetic Neuropathy total quality of life score (MD=−6.67, 95% CI=−9.70 to −3.64, p < 0.001), and a higher modified body mass index (MD=72.45, 95% CI=69.41 to 75.49, p < 0.001), with no significant difference in total adverse events [odds ratio (OR)=0.69, 95% CI=0.35 to 1.35, p=0.27]. The incidence of adverse events did not differ between tafamidis and placebo treatment except for fatigue (OR=0.13, 95% CI=0.02 to 0.72, p=0.02) and hypesthesia (OR=0.16, 95% CI=0.03 to 0.92, p=0.04). CONCLUSIONS: This systematic review and meta-analysis has demonstrated that tafamidis delays neurologic progression and preserves a better nutritional status and the quality of life. The rates of adverse events did not differ between the patients in the tafamidis and placebo groups. Tafamidis might be a safer noninvasive option for patients with TTR-FAP.
Amyloid Neuropathies ; Amyloid Neuropathies, Familial* ; Amyloidosis ; Bias (Epidemiology) ; Body Mass Index ; Extremities ; Fatigue ; Humans ; Hypesthesia ; Incidence ; Nutritional Status ; Polyneuropathies ; Population Characteristics ; Prealbumin* ; Publication Bias ; Quality of Life

Low-level laser therapy (LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals (12-33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group (LG) or a placebo group (PG) (1:1). The LG received LLLT (810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale (NRS) of pain, pressure pain thresholds (PPTs), cold detection thresholds (CDTs), warmth detection thresholds (WDTs), cold pain thresholds (CPTs), and heat pain thresholds (HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance (ANOVA). The NRS pain scores were significantly lower in the LG group (P = 0.01). The CDTs, CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG (P < 0.033). The parameters tested also showed significantly less sensitivity on the non-treatment side of the LG compared to that of the PG (P < 0.043). There were no differences between the groups for any quantitative sensory testing (QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment. Further clinical applications are suggested.
Adolescent ; Adult ; Female ; Humans ; Low-Level Light Therapy ; methods ; Male ; Pain Management ; Pain Measurement ; Pain Threshold ; physiology ; Tooth Movement Techniques ; adverse effects ; Toothache ; etiology ; radiotherapy ; Treatment Outcome ; Young Adult

Objective To summarize the clinical features of 22 probands diagnosed with congenital muscular dystrophy (CMD),and to provide genetic counseling and prenatal diagnosis for 23 fetuses of these pedigrees.Methods Data of 22 CMD patients who were treated in the Pediatric Department of Peking University First Hospital during October 2006 to March 2016 were analyzed.Informed written consents for participation in this study were obtained from the parents or guardians.Prenatal diagnosis was performed using DNA samples extracted from fetal villus cells of 12 cases at 11-13 gestational weeks and amniotic fluid of 11 cases at 18-22 gestational weeks.Direct DNA sequencing by polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) were used to detect CMD-related gene mutations.Linkage analysis of short tandem repeats (STRs) was used to identify maternal blood contamination and biological parents.Results Thirteen out of the 22 probands with CMD were diagnosed with congenital muscular dystrophy type 1 A (MDC1A),and all of them carried compound heterozygous mutations in LAMA2 gene.Prenatal diagnosis of 13 fetuses from these pedigrees found that four fetuses were wild-type,seven were heterozygotes and two carried the same mutations as their proband.Three probands with LMNA-related congenital muscular dystrophy (L-CMD) carried de novo mutations in LMNA gene.In these pedigrees,two fetuses were wild-type and one whose mother was mosaicism carried the same mutations as the proband.One proband with Ullrich congenital muscular dystrophy carried compound heterozygous mutations in COL6A2 gene and the fetus of the same pedigree was wild-type.Five probands were diagnosed with α-dystroglycanopathies.And among them,two cases of muscle-eye-brain disease (MEB) carried compound heterozygous mutations in POMGnT1 gene and the fetuses of the two peidgrees were heterozygotes;one case of congenital muscular dystrophy type 1C (MDC1C) had compound heterozygous mutations in FKRP gene and the fetus carried the same mutations;one patient diagnosed with POMGnT1-related congenital muscular dystrophy with mental retardation (CMD-MR) carried compound heterozygous mutations in POMGnT1 gene,and the fetus was positive for the same mutations;one proband with POMT1-related CMD-MR was positive for compound heterozygous mutations in POMT1 gene and the results of prenatal diagnosis for two fetuses of this pedigree showed that the first fetus had the same mutations as the proband,while the second was heterozygote.Conclusions No effective therapeutic method is available for CMD.Therefore,accurate genetic counseling and prenatal diagnosis are necessary to prevent CMD child from birth.