Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg^-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg^-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

OBJECTIVE：To systematically evaluate the efficacy and safety of Xianling gubao capsule combined with glucosamine in the treatment of knee osteoarthritis （KOA），and to provide evidence-based reference for clinical treatment of KOA. METHODS：Retrieved from Cochrane library ，PubMed，Embase，CNKI，Wanfang database ，CBM and VIP during the inception to Nov. 2020，randomized controlled trials （RCTs）about glucosamine （control group ）combined with Xianling gubao capsule （trial group）in the treatment of KOA were collected. After data extraction ，Cochrane 5.1.0 system evaluator manual was used to evaluate the quality of the included clinical studies met inclusion criteria ，and Rev Man 5.4 software was used for Meta-analysis. RESULTS ： A total of 11 RCTs with 970 patients were included in this study. Results of Meta-analysis showed that cure rate [OR ＝2.41，95％CI （1.48，3.93），P＜0.001]，marked effective rate [OR ＝1.95，95％CI（1.49，2.56），P＜0.001]，total effective rate [OR ＝4.00，95％CI （2.57，6.24），P＜0.001]，visual analogue scale （VAS）score [MD ＝－2.34，95％CI（－2.51，－2.17），P＜0.001]，knee function score [MD ＝31.32，95％CI（27.89，34.75），P＜0.001]，Japanese Orthopaedic Association （JOA）low back pain score [MD ＝ 12.22，95％CI（9.68，14.76），P＜0.001] and pain relief time [MD ＝－1.55，95％CI（－1.84，－1.25），P＜0.001] of trial group were all significantly better than those of control group. The incidence of ADR in trial group was significantly lower than control group [OR ＝0.04，95％CI（0.02，0.12），P＜0.001]. CONCLUSIONS ：Xianing gubao capsule combined with glucosamine in the treatment of KOA is significantly better in cure rate ，marked effective rate ，total effective rate ，VAS，score，knee function score，JOA low back pain score and pain relief time ，and could significantly reduce the incidence of ADR.

OBJECTIVE: To explore the genetic basis for a child suspected for hypokalemic periodic paralysis. METHODS: Clinical data of the patient was collected, and venous blood samples were taken from the patient and his parents for the extraction of genomic DNA. Next generation sequencing (NGS) with target capture was carried out to detect potential variants. Suspected variants were validated by Sanger sequencing. RESULTS: The child developed fatigue without obvious reason at the age of 15. Laboratory test revealed hypokalemia but normal serum magnesium. Genetic testing discovered that he has carried two variants in the SLC12A3 gene, namely c.179C>T and c.539C>A. The patient was diagnosed with Gitelman syndrome. CONCLUSION For children with hypokalemia, genetic testing should be considered for the differential diagnosis of Gitelman syndrome from hypokalemia due to other causes.

Objectives: To explore the impact of coronary atherosclerosis on diastolic function in patients with coronary heart disease. Methods: Present study included 600 patients with suspected coronary heart disease (CHD) admitted to our hospital between September 2014 to August 2017, coronary arteriography(CAG)was performed in all patients. Patients were divided into control group (n=150, CAG negative patients) , atherosclerosis group (n=150 ), and coronary heart disease group (n=300). Echocardiography, CAG, left ventriculography were measured in all patients, left ventricular diastolic function, coronary volume and pressure were compared among groups. Results: Left ventricular end-diastolic volume(LVEDV), left atrial volume index(LAVI) and left ventricular diastolic time constant (T) were significantly higher, while the ratio of early-to-late diastolic velocity (E/A) , the maximal rise velocity of left ventricular pressure (+dp/dtmax) , the maximum decrease velocity of left ventricular pressure (-dp/dtmax), the first third diastolic filling fraction (1/3 FF)and the last third of the diastolic filling fraction (p1/3 FF) were significantly reduced in the coronary atherosclerosis group and the coronary heart disease group as compared to control group (all P<0.05); left ventricular ejection fraction (LVEF) in CHD group was lower than that in control group (P<0.05); incidence of E/A<1.2 was significantly different among the 3 groups (P<0.01). Multivariate logistic regression analysis indicated that Gensini score was an independent risk factor for diastolic dysfunction(OR=1.93, 95%CI:1.31~2.68, P=0.01). The coronary artery end-diastolic volume (CEDV) , the coronary artery end-systolic volume ( CESV) , the maximum decrease velocity of coronary artery pressure (C-dp/dtmax), the maximum rise velocity of coronary artery pressure (C+dp/dtmax) were significantly decreased in the coronary sclerosis group (P<0.05) ; CEDV, CESV, C-dp/dtmax, C+dp/dtmaxwere significantly decreased in the coronary heart disease group (P<0.01) as compared with the control group. Compared with the coronary atherosclerosis group, the CEDV, CESV, C-dp/dtmax, C+dp/dtmaxwere significantly decreased in CHD group (P<0.05). CESV, C-dp/dtmax, C+dp/dtmax in the coronary sclerosis group were significantly decreased (P<0.05), CEDV, CESV, C-dp/dtmax, C+dp/dtmaxin the coronary heart disease group were significantly decreased (P<0.01).Compared with the coronary atherosclerosis group, the CEDV, CESV, C-dp/dtmax, C+dp/dtmaxwere significantly decreased in CHD group (P<0.05). Spearman correlation analysis showed that Gensini score was negatively correlated with C-dp /dtmax(r=-0.43, P<0.01). Conclusions:Diastolic dysfunction is a sensitive index of myocardial ischemia in patients with coronary heart disease. In patients with coronary atherosclerosis, cardiac diastolic dysfunction could be shown in the absence of cardiac systolic dysfunction. The severity of coronary atherosclerosis is positively related to coronary diastolic dysfunction, which may lead to decrease of coronary vascular compliance, thus induce cardiac diastolic dysfunction.

To further evaluate the effect of miR-217 in the proliferation of mouse adult pancreatic stem cells, we firstly transfected adult pancreatic stem cells with miR-217 mimics and studied the effect of miR-217 on proliferation through Western blot and immunofluorescence. Results showed that during the proliferation of adult pancreatic stem cells, miR-217 inhibited the protein expression of Ki-67 and Cyclin D1, which are related to cell propagation. As well as that, to investigate the target genes of miR-217 and their conserved sites bound by the seed region of miR-217, we used bioinformatic algorithms to find a potential target of miR-217 and verified by dual-luciferase activity assay. Surprisingly, dual-luciferase activity assay revealed that miR-217 could decrease PMIR-REPORT-Sirt1-3′UTR luciferase activity and Sirt1 is a direct target of miR-217. Finally, we verified the function of Sirt1 in the proliferation of pancreatic stem cells. Overexpression of miR-217 in pancreatic stem cells inhibited the level of Sirt1 in protein level but not in mRNA level. Furthermore, activator of Sirt1 played positive effect on colony formation ability and cell proliferation and inhibitor of Sirt1 showed the opposite function. In conclusion, miR-217 inhibits the proliferation of mouse adult pancreatic stem cells through Sirt1 and decreased expression of miR-217 to contribute to the pancreatic stem cells development.

PURPOSETo investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal (HPA) axis hormones in acute stress reaction in rats with wound and combined local radiation injury.

METHODSSixty female Wistar rats (weighting 200 ± 20 g) were randomly divided into normal control group, wound group and combined wound-local radiation (CWR) group (25 Gy local radiation post wound), 20 rats in each group. Contents of IL-1β, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone (ACTH) and glucocorticoid (GC) in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation.

RESULTS(1) The level of IFN-γ, one of the Th1 cell cytokines increased significantly at 14 d post CWR, which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1β and IL-6, one of the Th2 cell cytokines, did not show obvious change. (2) Ratio of Th1/Th2 (IFN-γ/IL-4) in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Th1/Th2 balance drifted to Th1 immune response. The ratio of Th1/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Th1/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. (3) Level of serous ACTH and GC in CWR group increased at 3 d post wound and radiation, and among them, level of GC showed statistically significant increase, which was much higher than that in control and wound groups.

CONCLUSIONLevel of serous neurohormone GC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes disturbance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR.