[Comparison of efficacy between personalized vestibular rehabilitation and otolith reposition for the treatment of atypical benign paroxysmal positional vertigo].

Objective: To compare the clinical efficacy of personalized vestibular rehabilitation and otolith reposition in treating atypical benign paroxysmal positional vertigo (BPPV). Methods: A randomized controlled trial was carried out. Fifty patients diagnosed with atypical BPPV in the Vertigo Clinic of the First Affiliated Hospital of Shandong First Medical University from October 2022 to September 2023 were recruited and randomly divided into manual reduction group (25 cases) and vestibular rehabilitation group (25 cases) according to the random number table. All patients were given flunarizine. Patients in the manual reduction group were treated by Epley maneuver and (or) Barbecue maneuver, while the vestibular rehabilitation group was given personalized vestibular rehabilitation therapy. After two weeks' treatment, the clinical symptoms (positional vertigo/nystagmus) and total dizziness handicap inventory (DHI) score, DHI physical (DHI-P), DHI emotional (DHI-E), and DHI functional (DHI-F) of the two groups were evaluated and compared. Results: A total of 50 patients diagnosed with atypical BPPV were included, including 23 males and 27 females, with an average age of (48.8±14.5) years. There was no statistically significant difference between the two groups in age, gender, disease severity, Romberg, position test abnormality ratio (Dix-hallpike/Roll test), temperature test, and video head impulse test baseline test results (all P>0.05). After 2 weeks of treatment, the effective rates of the treatment in the manual reduction and vestibular rehabilitation groups were 56.0% (14/25) and 88.0% (22/25), respectively, with a statistically significant difference (P=0.025). The total DHI score, DHI-P, DHI-E, and DHI-F scores in both groups were significantly decreased after treatment (all P<0.001). Compared with the manual reduction group, the total DHI score (23.2±2.7 vs 36.4±15.7, P=0.002), DHI-P (10.2±4.6 vs 13.7±5.3, P=0.016) and DHI-F (6.5±6.4 vs 13.0±7.2, P=0.002) in the vestibular group were lower, however, there was no significant difference in DHI-E score between the two groups (6.6±4.8 vs 9.6±7.3, P=0.087). Conclusion: Compared with otolith reposition, personalized vestibular rehabilitation therapy plays a better role in improving the symptoms and decreasing DHI score for patients with atypical BPPV.

[Research progresses on acute skin failure in children].

Acute skin failure (ASF) is an inevitable damage to the skin and subcutaneous tissue caused by hemodynamic instability and/or low perfusion. At present, there are some understandings and reports about adult ASF at home and abroad, but there are few reports about children's ASF. This article reviewed the definition, pathophysiological changes, risk factors, clinical manifestations, and management of children's ASF, and put forward suggestions in order to provide ideas for clinical diagnosis and treatment of children's ASF, and promote the further study of children's ASF.

Serum squamous cell carcinoma antigen level and magnetic resonance imaging for the prognosis of locally advanced cervical cancer.

OBJECTIVE: Squamous cell carcinoma antigen (SCC-ag) and magnetic resonance imaging (MRI) were explored to serve as biomarkers to predict the prognosis of cervical cancer (CC) patients treated with neoadjuvant chemotherapy (NACT) prior to radical surgery, with the aim of identifying the subgroup that least benefits from the combined therapy. PATIENTS AND METHODS: All patients were treated with NACT prior to radical surgery and received MRI and SCC-ag examinations before and after NACT. For these three cycles of NACT, patients were treated with intravenous paclitaxel at 150 mg/m2 over a period of 3 hours and carboplatin, with the area under the sera concentration-time curve of 5 over a period of 30 minutes on the first day of each cycle. Meanwhile, the blood pressure, ECG, and blood oxygen saturation of the patients were observed during the infusion. A discovery cohort and a validation cohort were applied to examine the prognostic performance of SCC-ag, MRI, and their combination. The endpoints of our study were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 384 patients diagnosed between August 2006 and December 2010 were enrolled in our research, with 206 patients in the discovery cohort and 178 patients in the validation cohort. The high-risk group identified by MRI had a worse OS [hazard ratio (HR), 3.567; 95% confidence interval (CI), 1.466-8.677; log-rank p=0.0027) and PFS (HR, 4.062; 95% CI, 2.171-7.6; log-rank p<0.0001) than the low-risk group. Meanwhile, the SCC-RC could serve as a strong prognostic factor to predict OS (HR, 5.614; 95% CI, 2.473-12.744; log-rank p<0.0001) and PFS (HR, 7.481; 95% CI, 4.194-13.344; log-rank p<0.0001) for CC. In addition, the combined MRI and SCC-ag had greater prognostic efficiency and were used to divide the whole patient population into three groups. Compared with patients in the low-risk group, patients in the high-risk group had a worse OS (HR, 8.216; 95% CI, 2.98-22.651; log-rank p<0.0001) and PFS (HR, 11.757; 95% CI, 5.735-24.104; log-rank p<0.0001). Multivariate analyses revealed that MRI, SCC-ag, and their combination were independent prognostic factors. CONCLUSIONS: SCC-ag and MRI, individually or in combination, were bound up with OS and PFS in CC. Additionally, the predictive efficiency improved when SCC-ag and MRI were combined in a risk model that predicted the OS and PFS of SCC compared with the predictive efficiency of either SCC-ag or MRI alone, revealing that the combination of these two biomarkers could help to ameliorate prognostic stratification and to guide personalized therapy for SCC patients.

[Secondary non-tuberculous mycobacterium infection in patients with bronchiectasis caused by Marfan syndrome].

In this article, we reported a 28-year-old female patient who presented with intermittent hemoptysis, cough, and sputum production. Laboratory tests showed no abnormalities in the blood counts or inflammatory markers, and the sputum cultures were negative. A chest computed tomography scan showed bronchiectasis associated with infection in the middle and lower lobes of the right lung and right pleural thickening. We performed bronchoalveolar lavage by bronchoscopy in the dorsal segment of the right lower lobe and found Mycobacterium avium intracellulare complex (MAC) by Next Generation Sequencing (NGS) of bronchoalveolar lavage fluid (BALF). The patient's symptoms improved significantly after anti-mycobacterium treatment and the extent of infection was reduced on imaging. To further identify the cause of bronchiectasis, the patient is tall and thin, with slender limbs. Cardiac color ultrasound showed the widening of aortic sinus. Her genetic testing of blood samples revealed the gene mutation in the FBN1 gene (c.4349G>A). Based on these results, she was diagnosed with Marfan syndrome.

[Report content and prenatal diagnosis of non-invasive prenatal testing for sex chromosome aneuploidy].

Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ2=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.

Identification and adaptive evolution analysis of glutaredoxin genes in Populus spp.

Glutaredoxin (GRX) is a class of small redox proteins widely involved in cellular redox homeostasis and the regulation of various cellular processes. The role of GRX gene in the differentiation of Populus spp. is rarely reported. We compared the similarities and differences of GRX genes among four sections of poplar using bioinformatics, corrected the annotations of some GRX genes, and focused on analysing their transcript profiling and adaptive evolution in Populus spp. A total of 219 GRX genes were identified in four sections of poplar, among which annotations for 13 genes were corrected. Differences in GRX genes were found between sect. Turanga, represented by P. euphratica, and other poplar sections. Most notably, P. euphratica had the smallest number of duplication events for GRX genes (n = 9) and no tandem duplications, whereas there were >25 duplication events for all other poplars. Furthermore, we detected 18 pairs of GRX genes under positive selection pressure in various sections of poplar, and identified two groups of GRX genes in the Salicaceae that potentially underwent positive selection. Expression profiling results showed that the PtrGRX34 and its orthologous genes were upregulated under stress treatments. In summary, the GRX gene family underwent expansion during poplar differentiation, and some genes underwent rapid evolution during this process, which may be beneficial for Populus spp. to adapt to environmental changes. This study may provide more insights into the molecular mechanisms of Populus spp. adaptation to environmental changes and the adaptive evolution of GRX genes.

[Molecular epidemiology and clinical characteristics of six cases of CA-MRSA pneumonia after influenza].

Objective: To summarize and analyze the strains' molecular epidemiology and clinical characteristics of 6 strains of post-influenza community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia. Methods: Six cases of CA-MRSA pneumonia after influenza from 2014 to 2022 were retrospectively collected and CA-MRSA strains from each patient were cultured. Then, SCCmec typing, MLST typing, and spa typing were performed on the samples, which also included the procedures for the detection of virulence factors. Antibiotic susceptibility test was then performed on all 6 strains. Results: ST59-t437-Ⅳ was the predominant type in all the strains of CA-MRSA(2/6). Leukocidin (PVL) was detected in 5 cases, and hemolysin α (HLAα) and phenol soluble regulatory protein α (PSMα) were detected in 6 cases. Five of the cases included in this study were diagnosed with severe pneumonia. In terms of treatment, 4 cases received antiviral therapy, and 5 patients with severe pneumonia received anti-infection treatment with vancomycin as the first choice and were discharged after improvement of their condition. Conclusions: The molecular types and virulence factors of CA-MRSA after influenza infection could vary considerably. Our experiments also showed that secondary CA-MRSA infection after influenza was more common in young people with no underlying diseases and could cause severe pneumonia. Vancomycin and linezolid were the first-line drugs for treating CA-MRSA infection and were highly effective in improving the condition of diagnosed patients. We highlighted the importance of referring patients with severe pneumonia after influenza for etiological tests to determine whether they had CA-MRSA infection, so that they could be properly treated with anti-influenza agents and receive appropriate anti-CA-MRSA infection treatment.

A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations.

BACKGROUND: For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest. PATIENTS AND METHODS: Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual. RESULTS: Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea. CONCLUSIONS: This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.

[Analysis of the pathogenesis and risk factors of gallstone].

Objective: To explore the pathogenesis and risk factors of gallstone formation. Methods: The findings of hepatobiliary ultrasound and related data were collected from healthy subjects who underwent a physical examination at Xuanwu Hospital of Capital Medical University from January 2012 to December 2021. A total of 98 344 healthy subjects were included in the study,including 48 241 males and 50 103 females,with a ratio of 1∶1.03,aged (42.0±15.6)years(range:14 to 97 years). The gender,age,body mass index,waist circumference,systolic pressure,diastolic pressure,ALT,AST,total bilirubin,fasting blood glucose,triglyceride,total cholesterol,low-density lipoprotein,high-density lipoprotein were collected.Healthy subjects were required to sit for at least 10 minutes before blood pressure was measured.Rresults of fasting venous blood were collected after 8 to 12 hours on an empty stomach.According to the presence of gallstones by ultrasound results, healthy subjects were divided into study group and control group. Data were analyzed by rank-sum tests and χ2 test, and risk factors for gallstone formation were explored by Logistic regression analysis. Results: The incidence of gallstones in this group was 5.42%(5 333/98 344). Among them,the incidence of gallstones in people aged 60 years and above was significantly higher than that in people under 60 years old(15.31%(2 348/15 334) vs. 3.60%(2 985/83 010), χ2=3 473.46,P<0.05).The healthy subjects were divided by age for every 10 years,and the results showed that the incidence of gallstones increased with age. The incidence of gallstones in females was 5.68%(2 844/50 103),greater than 5.16%(2 489/48 241) in males(χ2=11.81,P<0.05). Among them,1 478 cases underwent gallbladder surgical resection due to gallstones,and the operation rate was 27.71%. The operation rate reached the peak between 60 and <70 years old,and decreased after 70 years old. The results of the multivariate analysis showed that,female(OR=1.38, P<0.01),age(OR=1.58, P<0.01),body mass index≥24 kg/m2(OR=1.31, P<0.01),waist circumference≥85 cm(OR=1.24, P<0.01),fasting blood glucose>6.1 mmol/L(OR=1.18,P<0.01),total cholesterol≥5.18 mmol/L(OR=0.87, P=0.019),low-density lipoprotein≥3.37 mmol/L(OR=1.15,P=0.001) were the risk factors for gallstone formation;high-density lipoprotein≥1.55 mmol/L(OR=0.87, P<0.01) was a protective factor for gallstone formation. Conclusions: The incidence of gallstones increases with age in male and female. Gender,age,body mass index,waist circumferenc,fasting blood glucose,total cholesterol,LDL,and HDL are related factors with gallstone formation.

[Advances on pathogenesis of acquired peritoneal ultrafiltration failure in peritoneal dialysis].

Peritoneal ultrafiltration failure is a common reason for peritoneal dialysis (PD) withdrawal as well as mortality in PD patients. Based on the three-pore system, inter-cellular small pores and trans-cellular ultra-small pores (aquaporin-1) are mainly responsible for water transfer across the peritoneum. Both small and ultra-small pores-dependent water (free water) transport decline accompanied with time on PD, with more significant decrease in free water, resulting in peritoneal ultrafiltration failure. The reduction of free water transport is associated with fast peritoneal solute transfer, reduced crystalloid osmotic gradient due to increased interstitial glucose absorption, and declined osmotic conductance to glucose resulted from impaired aquaporin-1 function and peritoneal interstitial fibrosis. The decline of small pore-based water is mainly because of fast loss of crystalloid osmotic gradient, decrease of hydrostatic pressure mediated by peritoneal vasculopathy, as well as reduced absolute number of small pores. The current review discusses the advance on pathogenesis of acquired peritoneal ultrafiltration failure in long-term PD.

A new prognostic model for brain metastases of specific primary tumors with stereotactic radiotherapy.

PURPOSE: Stereotactic radiotherapy (SRT) was widely used in brain metastases (BM), especially in oligometastases. It is imperative to develop a new prognostic score to predict the overall survival (OS) of brain metastases based on prognostic factors for specific primary tumors. MATERIAL AND METHOD: One hundred and ninety-seven patients were involved in the training cohort to develop a new prognostic score to predict the overall survival (OS) of brain metastases for specific primary tumors. Independent prognostic factors were confirmed using a Cox regression model. The score was developed based on clinical prognostic factors of OS with Cox proportional hazards model. The result was validated in another cohort with 56 participants to evaluate the performance of the score. RESULTS: One hundred and ninety-seven patients with 329 brain metastases received SRT. For NSCLC, the significant prognostic factors were extracranial metastases, target therapy and number of brain metastases. For gastrointestinal cancer, the significant prognostic factors were target therapy and number of brain metastases. CONCLUSION: The prognostic factors scores were varied by the histologic types which can be used to efficiently stratify for selected patients with brain-metastasis.

[Effectiveness of 13-valent pneumococcal conjugate vaccine against invasive disease caused by serotype 19A in children: a meta-analysis].

Objective: Using Meta-analysis to evaluate the vaccine effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against invasive Streptococcus pneumoniae disease (IPD) caused by serotype 19A in children <5 years old. Methods: "Streptococcus pneumoniae infection""invasive pneumococcal disease""13-valent pneumococcal polysaccharide conjugate vaccine""PCV13""effectiveness""infant""child" and related terms were searched from China National Knowledge Infrastructure (CNKI), WANFANG DATA, PubMed, SCOPUS and Web of science with no limited on language, region and research institution. The retrieval time was limited from January 2010 to February 2023 and cohort study, case-control study and randomized controlled trial were included. Data were extracted from eligible studies by two independent reviewers, and after study quality assessment by NOS scale, Meta-analysis was completed using Stata 16.0 software. Results: A total of 2 340 related literatures were searched, and 10 literatures were finally included, including 5 case-control studies and 5 indirect cohort studies, which showed good literature quality. The vaccine effectiveness against serotype 19A IPD of PCV13 in children was 83.91% (95%CI: 78.92%-88.89%), and the subgroup analysis (P=0.240) showed there was no significant difference among the case-control study (VE=87.34%, 95%CI:79.74%-94.94%) and the indirect cohort study (VE=81.30%, 95%CI:74.69%-87.92%). The funnel plot and Egger test suggested that the possibility of publication bias was small. Conclusion: The present evidence indicates that PCV13 has a good vaccine effectiveness against serotype 19A IPD in children, and it is recommended to further increase the vaccination rate of PCV13 to reduce the disease burden of IPD in children <5 years old.

[Serology and genomic analysis of para-Bombay individuals in a hospital in Hunan Province].

To investigate the serological and genetic characteristics of para-Bombay patients in a hospital in Hunan Province. A retrospective analysis was conducted on the blood type results of 175 439 hospitalized patients born in Hunan Province from the Third Xiangya Hospital, Central South University from 2016 to 2021. Phenotypes of ABO blood group was analyzed by blood group serology, and molecular biological methods were used to analyze the genotype, including ABO genotyping by polymerase chain reaction-sequence specific primers (PCR-SSP) and fucosyltransferase 1 (FUT1) and fucosyltransferase 2 (FUT2) gene sequencing. The results showed that 3 cases of Ah and 1 case of Bh were detected. FUT1 sequencing showed that there were 2 cases of h3h3, 1 case of h1h1 and 1 case of h302h1, of which h302 (c.302C>T) was the first discovered mutation. FUT2 sequencing revealed that 4 cases were all Se357Se357. The pedigree study showed that the inheritance of para-Bombay blood group was consistent with autosomal dominant inheritance. In conclusion, the FUT1 gene mutations leading to para-Bombay blood group mainly include h3, h1 and h302, of which h3 mutation is the most common.

Pressure-induced monotonic enhancement of Tc to over 30 K in superconducting Pr0.82Sr0.18NiO2 thin films.

The successful synthesis of superconducting infinite-layer nickelate thin films with the highest Tc ≈ 15 K has ignited great enthusiasm for this material class as potential analogs of the high-Tc cuprates. Pursuing a higher Tc is always an imperative task in studying a new superconducting material system. Here we report high-quality Pr0.82Sr0.18NiO2 thin films with Tconset ≈ 17 K synthesized by carefully tuning the amount of CaH2 in the topotactic chemical reduction and the effect of pressure on its superconducting properties by measuring electrical resistivity under various pressures in a cubic anvil cell apparatus. We find that the onset temperature of the superconductivity, Tconset, can be enhanced monotonically from ~17 K at ambient pressure to ~31 K at 12.1 GPa without showing signatures of saturation upon increasing pressure. This encouraging result indicates that the Tc of infinite-layer nickelates superconductors still has room to go higher and it can be further boosted by applying higher pressures or strain engineering in the heterostructure films.

Effects of Non-Invasive Brain Stimulation on Alzheimer's Disease.

BACKGROUND: Previous meta-analyses did not explore the immediate and long-term effect of non-invasive brain stimulation (NIBS) on different cognitive domains in Alzheimer's disease (AD). The meta-analysis aimed to assess the therapy effect of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on different cognitive domains in AD in randomized controlled trials (RCTs). METHODS: Studies published before December 2021 and exploring therapy effect of rTMS, tDCS on different cognitive domains in AD were searched in the following databases: PubMed and Web of Science. We used STATA 12.0 software to compute the standard mean difference (SMD) and a 95% confidence interval (CI). RESULTS: The present study included 16 articles (including 372 AD patients treated with rTMS and 310 treated with sham rTMS) for rTMS and 11 articles (including 152 AD patients treated with tDCS and 134 treated with sham tDCS) for tDCS. The present study showed better immediate and long-term general cognitive function increase effects in AD given rTMS, compared to those given sham rTMS with random effects models (immediate effect: SMD = 2.07, 95% CI = 0.37 to 3.77, I2 = 97.8%, p < 0.001; long-term effect: SMD = 5.04, 95% CI = 2.25 to 7.84, I2 = 97.8%, p < 0.001). The present study showed no significant immediate and long-term effects of rTMS on attention, executive, language and memory functions. In addition, the present study showed no significant difference in immediate or long-term effects of tDCS on general cognitive function, attention, language or memory functions between tDCS group and sham tDCS group. CONCLUSIONS: RTMS was an effective treatment technique for general cognitive function in AD, whereas tDCS showed no significant therapy effect on cognitive function in AD. More large-scale studies were essential to explore the effect of NIBS on various cognitive function in AD.

Retention of Intrafibrillar Minerals Improves Resin-Dentin Bond Durability.

The concept of extrafibrillar demineralization involves selective removal of apatite crystallites from the extrafibrillar spaces of mineralized dentin without disturbing the intrafibrillar minerals within collagen. This helps avoiding activation of endogenous proteases and enables air-drying of partially demineralized dentin without causing collapse of completely demineralized collagen matrix that adversely affects resin infiltration. The objective of the present study was to evaluate the potential of quaternized carboxymethyl chitosan (QCMC)-based extrafibrillar demineralization in improving resin-dentin bond durability. Isothermal titration calorimetry indicated that QCMC synthesized by quaternization of O-carboxymethyl chitosan had moderate affinity for Ca2+ (binding constant: 8.9 × 104 M-1). Wet and dry bonding with the QCMC-based demineralization produced tensile bond strengths equivalent to the phosphoric acid (H3PO4)-based etch-and-rinse technique. Those bond strengths were maintained after thermocycling. Amide I and PO43- mappings of QCMC-conditioned dentin were performed with atomic force microscope-infrared spectroscopy (AFM-IR). Whereas H3PO4-etched dentin exhibited an extensive reduction in PO43- signals corresponding to apatite depletion, QCMC-conditioned dentin showed scattered dark areas and bright PO43- streak signals. The latter were consistent with areas identified as collagen fibrils in the amide I mapping and were suggestive of the presence of intrafibrillar minerals in QCMC-conditioned dentin. Young's modulus mapping of QCMC-demineralized dentin obtained by AFM-based amplitude modulation-frequency modulation recorded moduli that were the same order of magnitude as those in mineralized dentin and at least 1 order higher than H3PO4-etched dentin. In situ zymography of the gelatinolytic activity within hybrid layers created with QCMC conditioning revealed extremely low signals before and after thermocycling, compared with H3PO4-etched dentin for both wet and dry bonding. Confocal laser scanning microscopy identified the antibacterial potential of QCMC against Streptococcus mutans and Enterococcus faecalis biofilms. Taken together, the QCMC-based demineralization retains intrafibrillar minerals, preserves the elastic modulus of collagen fibrils, reduces endogenous proteolytic activity, and inhibits bacteria biofilms to extend dentin bond durability.

[Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development].

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

[Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing].

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.

Prostacyclins and pulmonary arterial hypertension in children.

OBJECTIVE: Despite its low incidence, pulmonary hypertension in children places a substantial burden on families and society because survival can be shorter than 10 months and treatment options are limited and ineffective. Drugs to treat pulmonary hypertension include endothelin antagonists, phosphodiesterase type 5 inhibitors and prostacyclin, which is the most widely used to treat pediatric pulmonary hypertension. The main aim of this study was to provide a comprehensive overview of the advantages and disadvantages of prostacyclin and its analogs for treating pulmonary hypertension in children. MATERIALS AND METHODS: To retrieve a thorough collection of studies, we performed a search in PubMed using the following combination of keywords: (Prostacyclins) or (Epoprostenol) or (Iloprost) or (Treprostinil) or (Beraprost), (children) and (pulmonary arterial hypertension). The time limits used for the search were December 1983 to May 2021. RESULTS: The search retrieved a total of 238 articles. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included. CONCLUSIONS: Epoprostenol can be effective against severe pulmonary hypertension. Iloprost can treat severe persistent pulmonary hypertension in newborns and inhaled iloprost can be used in pulmonary vasoreactivity testing. Treprostinil is a long-acting prostacyclin analog, and it shows the highest antiproliferative activity among prostacyclins. Beraprost may be effective in premature infants, but available evidence comes from only one patient, so more clinical testing is needed.

Ultra-low-dose estradiol and dydrogesterone: a phase III study for vasomotor symptoms in China.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ultra-low-dose estradiol plus dydrogesterone for vasomotor symptoms in postmenopausal women in China (trial registration CTR20160689). METHODS: A total of 332 patients were randomized to continuous combined estradiol 0.5 mg + dydrogesterone 2.5 mg or placebo for 12 weeks. The primary efficacy endpoint was change in the number of hot flushes per day from baseline to end of treatment. Secondary efficacy endpoints included change in the number of moderate-to-severe hot flushes per day, menopausal symptoms from baseline and quality of life. RESULTS: Between baseline and end of treatment, change in the mean number of hot flushes per day was -5.9 (95% confidence interval [CI] - 6.6, -5.2) with estradiol + dydrogesterone and -4.5 (95% CI -5.1, -3.8) with placebo, with a mean difference of -1.4 hot flushes per day (95% CI -2.2, -0.7; p < 0.001). Significant differences in favor of estradiol + dydrogesterone were also observed in several secondary efficacy endpoints. The study treatment was well tolerated. CONCLUSION: Continuous combined estradiol 0.5 mg + dydrogesterone 2.5 mg reduced hot flushes in postmenopausal women in China. This ultra-low-dose regimen provides an additional option for women experiencing the vasomotor symptoms of menopause. These data are consistent with previous results in other populations.