The adaptation of root cell wall pectin to copper toxicity in two citrus species differing in copper tolerance: remodeling and responding.

Citrus species are prone to suffer from copper (Cu) toxicity because of improper application of Cu-based agrochemicals. Copper immobilization mediated by pectin methylesterase (PME) in the root cell wall (CW) is effective for Cu detoxification. However, the underlying mechanisms of the structural modification and stress responses of citrus root CW pectin to Cu toxicity have been less discussed. In the present study, seedlings of 'Shatian pummelo' (Citrus grandis L. Osbeck) and 'Xuegan' (Citrus sinensis L. Osbeck), which differ in Cu tolerance, were irrigated with nutrient solution containing 0.5 (as control), 100, 300 or 500 µM Cu for 18 weeks in sandy culture or 24 h in hydroponics. At the end of treatments in the 18-week sandy culture, Cu toxicity on CW pectin content, Cu distribution, degree of pectin methylesterification (DPM) and the PME enzyme activity were discussed. At the genome-wide level, PME gene family was identified from the two citrus species, and qRT-PCR array of citrus PMEs under control and 300 µM Cu stress for 18 weeks were performed to screen the Cu-responsive PME genes. Moreover, the candidate genes that responded to Cu toxicity were further examined within 24 h. The results showed that Cu toxicity increased the root CW pectin content. The root CW pectin under Cu toxicity was remodeled by upregulation of the expression of the Cu-responsive PME genes followed by increasing PME activity, which mainly promoted low methylesterased pectin level and the Cu content on root CW pectin. Compared with C. sinensis, C. grandis root CW had a lower DPM and higher Cu content on the Cu-stressed root CW pectin, contributing to its higher Cu tolerance. Our present study provided theoretical evidence for root CW pectin remodeling in response to Cu toxicity of citrus species.

Theoretical analysis and practical applications of the catalytic mechanism of flavonoid 6-hydroxylase / 生物工程学报

Insufficient catalytic efficiency of flavonoid 6-hydroxylases in the fermentative production of scutellarin leads to the formation of at least about 18% of by-products. Here, the catalytic mechanisms of two flavonoid 6-hydroxylases, CYP82D4 and CYP706X, were investigated by molecular dynamics simulations and quantum chemical calculations. Our results show that CYP82D4 and CYP706X have almost identical energy barriers at the rate-determining step and thus similar reaction rates, while the relatively low substrate binding energy of CYP82D4 may facilitate product release, which is directly responsible for its higher catalytic efficiency. Based on the study of substrate entry and release processes, the catalytic efficiency of the L540A mutation of CYP82D4 increased by 1.37-fold, demonstrating the feasibility of theoretical calculations-guided engineering of flavonoid 6-hydroxylase. Overall, this study reveals the catalytic mechanism of flavonoid 6-hydroxylases, which may facilitate the modification and optimization of flavonoid 6-hydroxylases for efficient fermentative production of scutellarin.

Exploration of the relationship between the storage time of leukodepleted red blood cell and transfusion adverse reactions / 中国输血杂志

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

Excess Oxygen Supply for Different Time Periods Affect Energy Metabolism in Rat Alveolar Epithelial Type Ⅱ Cells / 中国医学科学院学报

Objective To observe the effect of excess oxygen supply for different time periods on the mitochondrial energy metabolism in alveolar epithelial type Ⅱ cells. Methods Rat RLE-6TN cells were assigned into a control group (21% O2 for 4 h) and excess oxygen supply groups (95% O2 for 1,2,3,and 4 h,res-pectively).The content of adenosine triphosphate (ATP),the activity of mitochondrial respiratory chain complex V,and the mitochondrial membrane potential were determined by luciferase assay,micro-assay,and fluorescent probe JC-1,respectively.Real-time fluorescence quantitative PCR was employed to determine the mRNA levels of NADH dehydrogenase subunit 1 (ND1),cytochrome b (Cytb),cytochrome C oxidase subunit I (COXI),and adenosine triphosphatase 6 (ATPase6) in the core subunits of mitochondrial respiratory chain complexes Ⅰ,Ⅲ,Ⅳ,and Ⅴ,respectively. Results Compared with the control group,excess oxygen supply for 1,2,3,and 4 h down-regulated the mRNA levels of ND1 (q=24.800,P<0.001;q=13.650,P<0.001;q=9.869,P<0.001;q=20.700,P<0.001),COXI (q=16.750,P<0.001;q=10.120,P<0.001;q=8.476,P<0.001;q=14.060,P<0.001),and ATPase6 (q=22.770,P<0.001;q=15.540,P<0.001;q=12.870,P<0.001;q=18.160,P<0.001).Moreover,excess oxygen supply for 1 h and 4 h decreased the ATPase activity (q=9.435,P<0.001;q=11.230,P<0.001) and ATP content (q=5.615,P=0.007;q=5.029,P=0.005).The excess oxygen supply for 2 h and 3 h did not cause significant changes in ATPase activity (q=0.156,P=0.914;q=3.197,P=0.116) and ATP content (q=0.859,P=0.557;q=1.273,P=0.652).There was no significant difference in mitochondrial membrane potential among the groups (F=0.303,P=0.869). Conclusion Short-term excess oxygen supply down-regulates the expression of the core subunits of mitochondrial respiratory chain complexes and reduces the activity of ATPase,leading to the energy metabolism disorder of alveolar epithelial type Ⅱ cells.

Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma / 生物医学与环境科学（英文）

OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Management of neonatal hyperbilirubinemia: interpretation of the clinical management guidelines drafted by the American Academy of Pediatrics and other countries / 中华实用儿科临床杂志

Neonatal hyperbilirubinaemia, clinically presenting as jaundice, is a ubiquitous and commonly a benign metabolic condition in newborn infants.It is a leading cause of hospitalization of neonates in the first week of life.Serum bilirubin has been considered as the most potent superoxide with the peroxyl radical scavenger activity.However, uncontrolled hyperbilirubinaemia or rapidly rising bilirubin can reach a neurotoxic concentration, potentially leading to central nervous system sequelae.Thus, the health status of jaundiced newborn infants is dependent on striking an appropriate balance between the protective effects of serum bilirubin and the risk of bilirubin neurotoxicity.In order to standardize the management of neonatal hyperbilirubinemia (jaundice), many countries have developed clinical practice management guidelines.This review sorted out and briefly interpreted the main contents of clinical management guidelines for neonatal hyperbilirubinemia drafted by the American Academy of Pediatrics and other countries, aiming to provide references of clinical diagnosis and treatment practice to domestic pediatrician.

Treatment of cancer-related fatigue based on "treating overstrain syndrome with warming methods" / 国际中医中药杂志

Cancer-related fatigue (CRF) belongs to the category of "consumptive disease" in TCM, and its occurrence is based on "internal deficiency" of the body causing by the tumor. Its nature is intermingled deficiency and excess. Its pathogenesis is the deficiency of qi, blood, yin and yang and zang-fu viscera dysfunction caused by disorders of "rise and fall of middle qi" and kidney origin depletion. The theory of "treating overstrain syndrome with warming methods" originates from Huang Di Nei Jing, which proposes that warming methods are the basic methods of treating consumptive disease. Therefore, starting from the cause and pathogenesis of CRF, this article sorted out the theoretical origin of "treating overstrain syndrome with warming methods", and discussed the clinical application of warming methods for the treatment of CRF combining with modern clinical research, with the purpose to provide references for clinical practice.

Prenatal Genetic Diagnosis and Origin Analysis of Rare Complete Translocation Trisomy 18 / 中山大学学报(医学科学版)

ObjectiveTo discuss the origin of rare abnormal karyotypes of fetuses with high risk of trisomy 18 revealed by non-invasive prenatal testing （NIPT） and its impact on fertility. MethodsThe cytogenetic and molecular genetic analyses were performed on the abnormal chromosomes of a prenatally diagnosed fetus with rare complete translocation trisomy 18. Using the keywords “translocation trisomy 18” or “trisomy 18 translocation” in both Chinese and English， we searched PubMed， CNKI， SinoMed， WanFang Data， CQ VIP and the Chinese Medicine database. The relevant case series were retrieved and critically appraised. ResultsG-banded karyotype analysis showed that the maternal karyotype was 46，XX，t（9；18）（q31.2；q23） and the fetal karyotype was 47， XN， t （9； 18） （q31.2；q23）mat， +18， which was a rare complete translocation type of trisomy 18. The SNP array revealed the fetus had increased copy number of chromosome 18 and two complete chromosome 18 inherited from the mother with balanced chromosomal translocation. Literature search found two children with complete translocation trisomy 18 reported abroad. Both of them had trisomy 18 phenotype and originated from the balanced translocation between parental chromosome 18 and other chromosomes. ConclusionNIPT gives an effective advance warning of trisomy 18. SNP array not only improves the detection rate of chromosomal abnormalities， but also helps identify the origin. The karyotype is still the gold standard for prenatal diagnosis.

Long-term prognostic analysis of different treatment strategies for T 3-T 4 nasal sinus adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the prognosis and influencing factors of different treatment strategies in T 3-T 4 nasal sinus adenocarcinoma. Methods:The data of 93 cases of T 3-T 4 stage nasal sinus adenocarcinoma diagnosed from 2006 to 2018 were retrospectively analyzed. All patients were divided into combined operation group and non-operation group. The survival status and failure mode after corresponding treatment were analyzed. The enumeration data were analyzed by Chi-square test or Fisher's exact test. Survival analysis was performed by Kaplan-Meier method. Univariate analysis was conducted by log-rank test. Multivariate prognostic analysis was performed by Cox model. Results:The average follow-up time in the whole cohort was 81.3 months (18-156 months). By the end of follow-up, a total of 38.7% (36/93) of patients had local recurrence, 14.0% (13/93) had distant metastasis, 17.2% (16/93) had local recurrence complicated with distant metastasis, and 28.0% (26/93) were stable. The overall 2-, 5-, and 10-year overall survival (OS) and progression free survival (PFS) rates were 83.5%, 59.3%, 31.8% and 73.6%, 40.7% and 25.3%, respectively. In univariate analysis, the PFS and OS of patients aged 46-64 years old (all P<0.001), male ( P=0.022, P=0.001), patients with lesions located in the maxillary sinus ( P=0.001, P<0.001), adenoid cystic carcinoma ( P=0.001, P<0.001), non-invasion of orbital / clivus ( P=0.041, P<0.001), GTV P dose>64 Gy ( P=0.003, P=0.006) and N 1 stage ( P=0.014, P=0.014) were statistically different among different treatment modes. Multivariate analysis showed that age ≥65 years old ( P=0.012, P=0.005), orbital / clival invasion ( P<0.001, P=0.005), and GTV p dose ≤64 Gy ( P<0.001, P=0.011) were the independent adverse prognostic factors affecting PFS and OS in T 3-T 4 stage nasal sinus adenocarcinoma. Conclusions:The local failure rate of T 3-T 4 stage nasal sinus adenocarcinoma is high after treatment. Age, orbital / clival invasion, and GTV p dosage are the independent adverse prognostic factors. Surgery based intervention is superior to other treatment strategies.

Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor / 中西医结合学报

OBJECTIVE@#This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR).@*METHODS@#Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.@*RESULTS@#Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.@*CONCLUSION@#Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.

Research progress of diabetic renal fibrosis / 中国药理学通报

Diabetic nephropathy (DN) is one of the most common and serious microvascular complications in patients with diabetes mellitus. Diabetic renal fibrosis ( DRF) is a major pathological change in the development of DN. In recent years the incidence of renal fibrosis (RF) has remained high. For diabetic patients, RF may expose them to kidney transplantation or even death, which brings a great burden to themselves and their families. Therefore, learning the pathogenesis and the current treat ment status of DRF is crucial for the treatment of the disease and the development of new drugs. Here we review the general situa¬tion of DN, the general situation, molecular mechanism, and the treatment of DRF,looking forward to providing a reference for the research and treatment of DRF.

A unique binding pocket induced by a noncanonical SAH mimic to develop potent and selective PRMT inhibitors

Protein arginine methyltransferases (PRMTs) are attractive targets for developing therapeutic agents, but selective PRMT inhibitors targeting the cofactor SAM binding site are limited. Herein, we report the discovery of a noncanonical but less polar SAH surrogate YD1113 by replacing the benzyl guanidine of a pan-PRMT inhibitor with a benzyl urea, potently and selectively inhibiting PRMT3/4/5. Importantly, crystal structures reveal that the benzyl urea moiety of YD1113 induces a unique and novel hydrophobic binding pocket in PRMT3/4, providing a structural basis for the selectivity. In addition, YD1113 can be modified by introducing a substrate mimic to form a "T-shaped" bisubstrate analogue YD1290 to engage both the SAM and substrate binding pockets, exhibiting potent and selective inhibition to type I PRMTs (IC50 < 5 nmol/L). In summary, we demonstrated the promise of YD1113 as a general SAH mimic to build potent and selective PRMT inhibitors.

The preventive and therapeutic effect of repetitive transcranial magnetic stimulation on radiation-induced brain injury in mice.

PURPOSE: To clarify the preventive and therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on brain injury induced by X-ray cranial irradiation, preliminarily identify the mechanism and provide a novel clinical approach for the prevention and treatment of radiation-induced brain injury (RBI). MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided into the sham group, large fractionated dose (5 Gy × 4 d) group, large fractionated dose + rTMS (5 Gy × 4 d + rTMS) group, conventional fractionated dose (2 Gy × 10 d) group and conventional fractionated dose + rTMS (2 Gy × 10 d + rTMS) group. After cranial irradiation and rTMS, behavioral experiments, morphological staining and molecular biology experiments were performed. We further determined the mechanism of rTMS on the prevention and treatment of RBI, including changes in hippocampal neuronal apoptosis, neural stem cell (NSC) proliferation and differentiation, and neuronal synaptic plasticity. RESULTS: rTMS alleviated the negative effects of cranial radiation on the general health of mice and promoted their recovery. rTMS ameliorated the impairment of spatial learning and memory induced by cranial radiation, and this beneficial effect was more robust in the conventional fractionated dose group than the large fractionated dose group. Moreover, rTMS alleviated the alterations in hippocampal structure and neuronal death and had preventive and therapeutic effects against RBI. In addition, rTMS reduced hippocampal cell apoptosis, promoted NSC proliferation and differentiation in the hippocampus after cranial irradiation, and enhanced neuronal synaptic plasticity in the hippocampus. Subsequent studies showed that rTMS upregulated the expression of learning- and memory-related proteins. CONCLUSION: rTMS could alleviate learning and memory impairment caused by RBI, and the preventive and therapeutic effects of rTMS were better for the conventional fraction radiation paradigms.

Management and prognosis of congenital chylous ascites in 20 infants / 中华围产医学杂志

Objective:To summarize the perinatal management and prognosis of congenital chylous ascites (CCA).Methods:Clinical data of 20 infants diagnosed with CCA and treated in Guangdong Women and Children Hospital from June 2015 to November 2020 were retrospectively analyzed and described.Results:There were ten patients with isolated CCA and ten with non-isolated CCA. In isolated CCA cases, seven were cured after conservative treatment and three after postoperative conservative treatment following an ineffective surgery. Non-isolated CCA cases were complicated by intrauterine cytomegalovirus infection ( n=1), malrotation of intestine ( n=4) or bilateral chylothorax ( n=5). In addition to conservative treatment for CCA, non-isolated CCA patients also received antiviral therapy, Ladd's procedure or intrauterine/extrauterine closed thoracic drainage. Of eight patients who were firstly diagnosed with ascites before 30 gestational weeks, including four isolated and four non-isolated cases, only one underwent surgical intervention. During hospitalization, serious infections occurred in three infants with isolated CCA and two with non-isolated CCA, and were all controlled by anti-infection treatment. During a follow-up to median age of 29 months (15-82 months), none of the patients had any abnormalities except for the one with intrauterine cytomegalovirus infection who was deaf at the age of two. Conclusions:Conservative management is effective and the prognosis is generally good for most cases with isolated CCA. Treatment and prognosis of non-isolated CCA depend on its comorbidities. Gestational age at diagnosis may not be a prognostic predictor.

Research progress of referral after screening for mild cognitive impairment in older adults / 中华老年医学杂志

The prevalence of mild cognitive impairment(MCI) is increasing.Screening and early intervention on MCI patients can effectively delay the course of the disease and improve the outcome.However, the visit rate of MCI in China is less than 4‰, and the majority of the patients did not receive the relevant health services.The referral is the key steps between patient screening and getting the follow-up health service, which is currently the weakest link.This review discusses the status of referral after MCI screening in recent years, summarizes and analyzes the factors influencing the referral from three aspects of the recipients, donors and environment.We also summarized interventions to improve the referral rate, which provided the theoretical foundation for improving the medical behavior in patients with MCI, so as to make patients receive proper treatment and care for reducing the country-related burden of disease.

Clinical exploratory study on reduction of clinical target volume in postoperative intensity-modulated radiotherapy for parotid gland cancer / 中华放射肿瘤学杂志

Objective:To evaluate the effect of reducing clinical target volume (CTV) on local control and overall survival in postoperative intensity-modulated radiotherapy (IMRT), and analyze the patterns of failure, aiming to provide clinical basis for postoperative IMRT delineation of CTV for parotid gland cancer in the era of precision radiotherapy.Methods:Clinical data of 126 patients who were pathologically diagnosed with parotid gland cancer and treated with parotidectomy as well as postoperative radiotherapy were retrospectively analyzed. All patients were divided into two groups according to the prozone of CTV. It was delineated to the anterior border of parotid gland in group A, and delineated to the anterior border of masseter in group B. Actuarial estimates of local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival and overall survival were obtained with the Kaplan-Meier method. Univariate prognostic analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by Cox regression model.Results:The 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS) and overall survival (OS) in groups A and B were 96.7% vs. 91.3%, 96.7% vs. 90.2%, 86.9% v s. 81.3% and 86.0% vs. 81.4%, respectively. There were no significant differences in these parameters between two groups. Of 126 patients with parotid carcinoma, 7 had local recurrence. There were 2 cases in group A which 1 recurred in-field and 1 recurred out- field. And there were 5 cases in group B which 4 recurred in-field and 1 recurred marginally. Univariate analysis showed that age was associated with LRFS. Age, N stage and pathological grading were associated with OS. Cox multivariate analysis revealed that age, N stage and pathological grading were the independent influencing factors of OS. Conclusions:Reducing the CTV would not increase the risk of local recurrence in patients with parotid gland carcinoma without tumor extravasation and negative surgical margins. There is no significant difference in survival benefit compared to those delineated to the anterior border of the masseter muscle. The delineation of CTV should be treated differently according to the risk factors.

Clinical value of Ki-67 and human epidermal growth factor receptor 2 in stage Ⅲ-Ⅳ A salivary duct carcinoma / 中华放射医学与防护杂志

Objective:To explore the clinical value of Ki-67 and human epidermal growth factor receptor 2 (HER-2) in salivary duct carcinoma in stage Ⅲ-Ⅳ A. Methods:The data of 52 cases of locally advanced salivary duct carcinoma(SDC) diagnosed from January 2012 to December 2020 were retrospectively analyzed. All patients underwent radical surgery and postoperative radiotherapy. Among them, 15.4% of patients had local recurrence, 28.8% had distant metastasis, 17.3% had regional recurrence with distant metastasis. The relationship between clinical features, pathological features such as Ki-67 and HER-2 and prognosis such as local recurrence and distant metastasis was analyzed.Results:The average follow-up time was 37.6 months. The 1- and 2-year local recurrence free survival, distant metastasis free survival, progression free survival were 86.5%, 73.1%, 65.4% and 67.3%, 55.8%, 46.2% respectively. The 3-year progression free survival rate was 33.3%. Comparison between groups showed that age ≥ 65 years old, T stage, TNM stage, vascular tumor thrombus, radiotherapy dose <60 Gy, Ki-67 positive index and HER-2 positive were related to the prognosis of different stages. In multivariate analysis, only age, Ki-67 positive index ≥ 60% and HER-2 protein (3+ ) were independent poor prognostic factors for locally advanced SDC ( t =5.16, 9.84, 8.23, P<0.05). Conclusions:In stage Ⅲ-Ⅳ A SDC, only radical surgery and postoperative radiotherapy have a high rate of distant metastasis. Ki-67 positive index and HER-2 positive are independent adverse prognostic factors.

Analysis of lactate dehydrogenase gene polymorphisms and prediction of B cell epitopes in four human Plasmodium species / 中国血吸虫病防治杂志

Objective To analyze the polymorphism of Plasmodium lactate dehydrogenase (pLDH) gene and predict B-cell epitopes in pLDH peptides in four species of human malaria parasites. Methods The blood samples and epidemiological characteristics were collected from malaria cases in Yunnan Province registered in the National Notifiable Disease Report System. The pLDH genes of four human Plasmodium species were amplified using nested PCR assay and sequenced. The polymorphisms of pLDH genes was analyzed using the software MEGA version 7.0.26 and DnaSP version 5.10, and the B-cell epitopes were predicted in pLDH peptides using the Immune Epitope Database (IEDB). Results The sequences of P. vivax LDH (PvLDH), P. falciparum LDH (PfLDH), P. ovale LDH (PoLDH) and P. malariae LDH (PmLDH) genes were obtained from 153, 29, 17 and 11 blood samples from patients with P. vivax, P. falciparum, P. ovale and P. malariae malaria, respectively, which included 15, 2, 4 and 2 haplotypes and had a nucleotide diversity (π) of 0.104. A high level of intra-species differentiation was seen in the PoLDH gene (π = 0.012), and the π values were all < 0.001 for PvLDH, PfLDH and PmLDH genes. Active regions of B-cell antigen were predicted in the pLDH peptide chain of four human malaria parasites, of 4 to 5 in each chain, and the activity score was approximately 0.430. Among these peptide chains, the “86-PGKSDKEWNRD-96” short-peptide was a B-cell epitope shared by all four species of human malaria parasites, and the “266-GQYGHS (T)-271” short-peptide was present in PvLDH and PoLDH peptide chains, while “212-EEVEGIFDR-220” was only found in the PvLDH peptide chain, and “208-LISDAE-213” was only seen in the PfLDH peptide chain. Conclusions The PoLDH gene polymorphism may be derived from the weak negative purification selection, while PvLDH, PfLDH and PmLDH genes may maintain a relatively conservative state. There may be two B-cell epitopes “212-EEVEGIFDR-220” and “208-LISDAE-213” in the proximal region of the C terminal in the pLDH peptide chain, which is feasible to differentiate between P. vivax and P. falciparum infections.

Metabolomic changes of neonatal sepsis: an exploratory clinical study / 中国当代儿科杂志

OBJECTIVES@#To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission.@*METHODS@#A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points.@*RESULTS@#On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism.@*CONCLUSIONS@#The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

Obstructive Sleep Apnea in Pregnancy / 中国医学科学院学报

The incidence of obstructive sleep apnea (OSA) is higher in pregnancy than in non-pregnancy,and obesity is a major risk factor.OSA in pregnancy can lead to multiple organ dysfunction and is associated with hypertensive disorders in pregnancy,gestational diabetes mellitus,premature birth,and fetal growth restriction. Therefore,early screening and diagnosis are essential for the prevention and treatment of OSA in pregnancy.