Objectives:To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared.Results:A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods ( P=0.008) . Conclusions:mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

Objective To investigate the effect of lifestyle on high-altitude de-adaptation(HADA)through questionnaire during the whole process of entering and existing the plateau in order to provide scientific basis for prevention and treatment of the disease.Methods A case-control trial was conducted on 1 751 participants from a certain unit who entered and existed the plateau together during 2021 and 2022.In 1 to 2 weeks after they returning from the plateau,they were surveyed,and finally,1 544 valid questionnaires were obtained.According to the score of the plateau deacclimation scale ≥6 or not,the subjects were divided into plateau deacclimation group(n=192)and control group(n=1 352).They were further surveyed for their lifestyles and general conditions.Rank sum test was used to analyze the differences of lifestyles between the 2 groups,and unconditional logistic regression analysis was employed to identify the independent risk factors of HADA.Results Hair loss(19.95％),drowsiness(16.58％)and tiredness(12.31％)were the most common symptoms of HADA.High salt diet before entering the plateau,smoking at the plateau,altitude sickness(OR=1.893,95％CI:1.142～3.137,P=0.013),leaving the plateau by plane(OR=1.688,95％CI:1.082～2.634,P=0.021),and drinking much tea,excessive exercise intensity and insufficient sleep after leaving the plateau were independent risk factors for HADA.Conclusion Low salt diet before entering the plateau,active prevention for altitude sickness,smoking cessation at the plateau,taking a slower means of transportation to enter and leave the plateau,drinking less tea,moderate exercise intensity and keeping enough sleep after leaving the plateau can effectively reduce the risk of HADA.

Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

The new medical reform takes the major aim to facilitate the expansion of high-quality medical resources and balance the regional distribution of the resources so as to meet the people's growing demand for high-quality healthcare.To exem-plify the expansion and balance of the high-quality resources,this paper scrutinizes the cooperation between aiding and aided hos-pitals by taking a state-level regional medical center hospital in Guizhou Province as an example.With cooperation-oriented pro-jects,the hospital achieved a homogenized development with the hospitals in developed regions in management,personnel,tech-nology,discipline,and hospital culture by introducing the high-quality resources from those hospitals.Such homogenized devel-opments empower the high-quality development of health care services in the less-developed regions of southwest China.Further-more,the experience of the hospital offers a reference for the development of other aided hospitals of state-level regional medical centers under new circumstances.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

BACKGROUND: Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial. METHODS: We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation (MSDT) for patients with AML in CR1 in multicenters across China. In our study, we analyzed data of 373 AML patients in CR1 from three centers across China. RESULTS: With a median follow-up of 969 days, patients with ≥ 3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival (LFS) (85.6% vs . 67.0%, P < 0.001) and overall survival (89.2% vs . 78.5%, P  = 0.007), and better cumulative incidences of relapse (10.5% vs . 19.6%, P  = 0.020) and non-relapse mortality (4.2% vs . 14.9%, P  = 0.001) than those with ≤ 2 courses of consolidation chemotherapy. Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with ≥ 3 courses of consolidation chemotherapy had a higher probability of LFS (85.9% vs . 67.7%, P  = 0.003) and a lower cumulative incidence of relapse (9.6% vs . 23.3%, P  = 0.013) than those with ≤ 2 courses. CONCLUSION Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.
Humans ; Retrospective Studies ; Consolidation Chemotherapy/methods* ; Siblings ; Hematopoietic Stem Cell Transplantation/methods* ; Leukemia, Myeloid, Acute/etiology* ; HLA Antigens ; Allografts

Objective:To explore the clinical value of recurrent laryngeal nerve dissection in the surgical treatment for congenital pyriform sinus fistula（CPSF）. Methods:The clinical data of 42 patients with CPSF were retrospectively analyzed. All patients were diagnosed and treated in the First Affiliated Hospital of Guangdong Pharmaceutical University. Results:During the operation, all patients' recurrent laryngeal nerves were dissected successfully, and fistulas were resected completely,no patients had complication of recurrent laryngeal nerve's damage.There were no recurrence cases during the 13 to 48 months of follow-up. Conclusion:The trend of congenital pyriform sinus fistula is closely related to recurrent laryngeal nerve, it's important to dissect the recurrent laryngeal nerve during the operation for congenital pyriform sinus fistula.
Humans ; Neck ; Recurrent Laryngeal Nerve/surgery* ; Retrospective Studies ; Pyriform Sinus/surgery* ; Fistula/surgery*

Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.

Objective:To explore risk factors for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-ALL).Methods:A retrospective analysis was performed for 65 adult Ph-ALL patients undergoing initial allo-HSCT from 2016 to 2018. The effect of baseline level and treatment pre-transplantation for relapse after allo-HSCT was analyzed.Results:There were 37 males and 28 females with a median age of 25(14-58) years during allo-HSCT. And the median follow-up period was 27 months post-HSCT. The 2-year overall survival (OS) was 78.8%(95%CI 67.8%-89.8%) and the 2-year relapse-free survival (RFS) 70.7% (95%CI 58.2%-83.2%). Pre-transplant chemotherapy was offered for 3 to 7 courses and the median dose of polyethylene glycol-conjugated asparaginase (PEG-ASP) was 3 doses (2 000 IU/m 2 per dose). Multiariate analysis revealed that the regimen included more than 4 doses of PEG-ASP pre-HSCT (HR=4.067, P=0.046) was a protective factor for post-transplant relapse (HR=0.193, P=0.009). High-risk chromosome karyotype was a risk factor for relapse (HR=0.193, P=0.009). The 2-year RFS rate was 90.0%(95%CI 79.2%-100.0%) for intensive PEG-ASP group and 56.9%(95%CI 39.1%-74.7%) for control group ( P=0.01). No significant inter-group difference existed in overall survival (OS)( P=0.079). The 2-year OS was 90.6% (95%CI 80.4%-100.0%) in intensive PEG-ASP group and 72.1% (95%CI 56.6%-87.6%) in control group. Conclusions:For adult ph-ALL patients, a higher dose of PEG-ASP in pretransplant chemotherapy regimens may improve post-transplant RFS and achieve a better outcome.

Objective:To investigate the effect of forkhead box protein A2(FOXA2) on cell proliferation, migration and invasion of hepatocellular carcinoma and the potential molecular mechanism.Methods:From January 2019 to December 2020, 10 cases of hepatocellular carcinoma patients from Zhongnan Hospital of Wuhan University were collected for study, including 7 males and 3 females, with an average age of 53 years. FOXA2 expression was detected in human liver cancer cell line, and the highest expression of FOXA2 was found in HepG2 cells transfected with FOXA2 overexpression plasmid. Immunohistochemistry and qRT-PCR were used to detect the expression of FOXA2. Western blot was used to detect the expression of FOXA2, hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial growth factor A (VEGFA), B-cell lymphofactor-2 (Bcl-2), matrix metalloproteinase (MMP) 7, and glucose transporter (GLUT) 1. EdU assay was used to study cell proliferation, and Transwell chamber assay was used to study cell migration and invasion.Results:The relative expression of FOXA2 in liver cancer tissues were lower than those in adjacent tissues both at mRNA and protein levels, with statistical significance (both P<0.05). FOXA2 overexpression group showed lower cell proliferation rate (30.0±3.2)%, migration rate (10.6±1.1), and invasion rate (12.8±0.8) comparing with negative control group (67.0±3.6)%, (81.0±5.4), (74.8±4.5). The difference was statistically significant (all P<0.05). Expression of HIF-1α and its downstream targets VEGFA, MMP7, GLUT1 and Bcl-2 was decreased after over-expression of FOXA2 in HepG2 cells. Conclusion:FOXA2 inhibits proliferation, migration, and invasion in hepatocellular carcinoma by regulating HIF-1α signaling pathway, suggesting that FOXA2 is a potential target for the treatment of hepatocellular carcinoma.