Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective:To explore the long-term efficacy of laparoscopic fundoplication for proton pump inhibitor dependent gastroesophageal reflux disease (GERD).Method:Clinical data of proton pump inhibitor dependent GERD patients who underwent fundoplication at the Rocket Force Characteristic Medical Center from Jan to Jun 2012 were analyzed, including GERD symptom score, subjective symptom relief rate, PPI discontinuation rate and surgical satisfaction, as well as recurrence and complications.Result:A total of 160 GERD patients were included in this study, with 64% of patients having respiratory symptoms. Nissen and Toupet fundoplication were performed in 43 and 117 cases, respectively, with a follow-up time of (127±3) months. The postoperative GERD symptom scores of the patients were significantly lower than before treatment (all P<0.001); The subjective relief of overall symptoms in the digestive tract and airway problem was 90% (80%, 100%) and 100%, respectively. The PPI discontinuation rate was 86%, and the overall satisfaction rate of the treatment was 92%, and the satisfaction rate of patients with respiratory symptoms was 89%. 7% of patients experienced varying degrees of symptomatic recurrence, 4% of patients re-underwent endoscopic treatment and/or laparoscopic fundoplication due to symptom recurrence. The incidence of long-term postoperative dysphagia, bloating, belching, increased exhaust, abdominal pain, diarrhea, and constipation were 11.3%, 16.9%, 0, 1.3%, 0, 2.5%, and 5.6%, respectively. Conclusions:Laparoscopic fundoplication has good long-term efficacy in the treatment of GERD. A small number of patients may experience postoperative recurrence, as well as complications such as dysphagia and gas-bloat syndrome. Most recurrent patients can achieve good therapeutic effect by redoing endoscopic treatment or redoing surgery.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.

Background: Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. Materials and Methods: We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). Results: Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network metaanalysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection–naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. Conclusion Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

The number of pediatric coronavirus disease 2019 (COVID-19) cases worldwide are increasing compared to the early phase of the pandemic, along with highly transmissible severe acute respiratory syndrome coronavirus variant and the increase in adult COVID-19 vaccination.We conducted a rapid systematic review and meta-analysis of published randomized clinical trials (RCTs) of the COVID-19 vaccines and the observational retrospective studies on adverse events after COVID-19 vaccination in adolescents. Seventeen studies were finally included in this systematic review. Meta-analysis showed that although vaccination in adolescents was significantly effective to prevent COVID-19 infection in retrospective studies (risk ratio [RR], 0.29; 95% confidence interval [CI], 0.22–0.37; I2 =100%), however the effect of preventing COVID-19 infection was lower than in RCTs (RR, 0.05; 95% CI, 0.01–0.27). In five retrospective studies, the pooled estimated proportion of participants with myocarditis and/or pericarditis was 2.33 per 100,000 of the population (95% CI, 0.97–5.61 per 100,000). Sub-group analysis with sex and vaccine doses showed that male (5.35 per 100,000) and the second dose (9.71 per 100,000) had significantly higher incidence of myocarditis and/or pericarditis than female (1.09 per 100,000) and the first dose (1.61 per 100,000), respectively. Our study showed that mRNA COVID-19 vaccines in adolescent recipients were favorable and effective against COVID-19 in RCT as well as observational studies. The safety findings of BNT162b2 vaccine in adolescents were explored and we found the difference of safety according to sex and vaccine doses. The occurrence of adverse events after mRNA COVID-19 vaccination should be monitored.