OBJECTIVES: To investigate the epidemiological characteristics of human metapneumovirus (hMPV) and the risk factors for severe pneumonia in hospitalized children. METHODS: The epidemiological characteristics of hMPV in hospitalized children at Hebei Children's Hospital from January 2019 to December 2023 were retrospectively analyzed. The clinical data of hospitalized children with hMPV infection from April to December 2023 were included, and independent risk factors for severe pneumonia were identified through logistic regression. RESULTS: A total of 44 092 children were tested, with an hMPV positive rate of 7.30% (3 220/44 092). Children aged 3-6 years constituted the largest proportion (40.93%, 1 318/3 220) among hMPV-positive cases. The detection rate varied significantly by year (P<0.001), peaking in 2022 (12.35%, 978/7 919). The peak season of the epidemic was winter and spring from 2019 to 2021, but shifted to spring and summer from 2022 to 2023. The proportion of co-infection was 38.70% (1 246/3 220), primarily with rhinovirus (600/1 246, 48.15%), Mycoplasma pneumoniae (217/1 246, 17.42%), and respiratory syncytial virus (182/1 246, 14.61%). The main manifestations of hMPV pneumonia were cough, expectoration, and fever. Children with severe pneumonia were significantly younger (P<0.05). Wheezing, underlying diseases, co-infection, and younger age were identified as independent risk factors for severe pneumonia (P<0.05). CONCLUSIONS There are significant annual and seasonal differences in the epidemiological characteristics of hMPV in hospitalized children. Young age, underlying diseases, wheezing, and co-infection are independent risk factors for severe pneumonia.
Humans ; Risk Factors ; Metapneumovirus ; Child, Preschool ; Child ; Male ; Female ; Paramyxoviridae Infections/complications* ; Pneumonia/epidemiology* ; Retrospective Studies ; Child, Hospitalized ; Infant ; Logistic Models ; Seasons ; Hospitalization

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Middle Aged ; Female ; Lung Neoplasms/pathology* ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Chemotherapy, Adjuvant ; Patient Reported Outcome Measures ; Quality of Life ; Aged ; Postoperative Period ; Prospective Studies

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.
Pregnancy ; Female ; Mice ; Humans ; Animals ; Spleen ; Ghrelin ; Fetal Weight ; Cholesterol, LDL ; Diarrhea

Professor SHAO Jing-ming's clinical experience of fire needling for bone-joint tuberculosis, tuberculous cervical lymphadenitis, ganglion cyst and thyrophyma is summarized. Professor SHAO used fire needling to treat bone-joint tuberculosis. The acupoints included ashi points and nearby acupoints, particularly local opposite acupoints (Neixiyan [EX-LE 4] and Dubi [ST 35], Yinlingquan [SP 9] and Yanglingquan [GB 34], Xuehai [SP 10] and Liangqiu [ST 34]), and for the patients with severe yin-cold syndrome, Yanghe decoction was additionally used. For tuberculous cervical lymphadenitis, fire needling was used at different stages. In the early stage, the nucleus was punctured with fire needling; in the middle stage, the pustule was punctured with fire needling combined with cupping; in the late stage, the fire needling was inserted into the fistula or sinus tract, and the surrounding granulation tissue was treated with horizontal penetrating needling. For ganglion cyst, fire needling combined with centro-square needling was applied. For thyrophyma, the surrounding needling with filiform was used; for simple thyroid mass and thyroid nodule, the surrounding needling with fire needling was used.
Acupuncture Points ; Acupuncture Therapy ; Ganglion Cysts ; Humans ; Lymphadenitis ; Tuberculosis, Osteoarticular

OBJECTIVE: Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis (AR). However, the results are inconclusive. We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR. METHODS: A total of 2,348 pregnant women from Ma'anshan, Anhui Province, China, who were screened before antenatal visits and met the inclusion criteria, were included in the present study. We assessed AR in their offspring aged 36 months with a questionnaire. Quantitative PCR was performed to measure placental inflammatory factor mRNAs. The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates. RESULTS: Childhood AR may be related to education and family monthly income ( P = 0.01). The phthalate metabolites, mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyl) phthalate (MEHHP), in pregnant women were associated with a significantly increased risk for infant AR in males [ P < 0.05; odds ratio ( OR): 1.285; 95% confidence interval ( CI): 1.037-1.591, and OR: 1.232, 95% CI: 1.008-1.507, respectively], but not females. Additionally, irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants ( OR: 1.175; 95% CI: 1.038-1.329 and OR: 1.181; 95% CI: 1.056-1.322, respectively). The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis. CONCLUSION The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant. Placental HO-1 was a fractional mediator in the associations between MEHHP and AR. Thus, the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.
Biomarkers ; Child, Preschool ; Cohort Studies ; Diethylhexyl Phthalate/analogs & derivatives* ; Female ; Humans ; Interleukin-4/pharmacology* ; Male ; Maternal Exposure/adverse effects* ; Phthalic Acids/adverse effects* ; Placenta ; Pregnancy ; Rhinitis, Allergic/epidemiology*

Diabetes-associated liver injury becomes a dominant hepatopathy, leading to hepatic failure worldwide. The current study was designed to evaluate the ameliorative effects of ginsenoside Rh1 (G-Rh1) on liver injury induced by T2DM. A T2DM model was established using C57BL/6 mice through feeding with HFD followed by injection with streptozotocin at 100 mg·kg^-1.. Then the mice were continuously administered with G-Rh1 (5 and 10 mg·kg^-1), to explore the protective effects of G-Rh1 against liver injury. Results showed that G-Rh1 exerted significant effects on maintaining the levels of FBG and insulin, and ameliorated the increased levels of TG, TC and LDL-C induced by T2DM. Moreover, apoptosis in liver tissue was relieved by G-Rh1, according to histological analysis. Particularly, in diabetic mice, it was observed that not only the increased secretion of G6Pase and PEPCK in the gluconeogenesis pathway, but also inflammatory factors including NF-κB and NLRP3 were suppressed by G-Rh1 treatment. Furthermore, the underlying mechanisms by which G-Rh1 exhibited ameliorative effects was associated with its capacity to inhibit the activation of the Akt/FoxO1 signaling pathway induced by T2DM. Taken together, our preliminary study demonstrated the potential mechnism of G-Rh1 in protecting the liver against T2DM-induced damage.
Animals ; Chemical and Drug Induced Liver Injury, Chronic ; Cholesterol, LDL/pharmacology* ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Forkhead Box Protein O1/pharmacology* ; Ginsenosides ; Insulin/metabolism* ; Liver ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Streptozocin

Objective: To summarize the clinical features, management and outcome of superior vena cava syndrome (SVCS) associated with mediastinal malignancy in children. Methods: Clinical data of 42 children of SVSC associated with mediastinal malignancy in Shanghai Children's Medical Center from January 2015 to December 2021 were collected and analyzed retrospectively. The clinical manifestations, pathological diagnosis, disease diagnosis process, and prognosis were summarized. Results: Among 42 children of SVCS associated with mediastinal malignancy, there were 31 males and 11 females. The age at diagnosis was 8.5 (1.9, 14.9) years. Cough and wheezing (33 cases, 79%), orthopnea (19 cases, 45%) and facial edema (18 cases, 43%) occurred most commonly. T-cell lymphoblastic lymphoma (T-LBL) was the most frequent pathological diagnosis (25 cases, 60%), followed by T-cell acute lymphoblastic leukemia (T-ALL) (7 cases, 17%), anaplastic large cell lymphoma (4 cases, 10%) and diffuse large B-cell lymphoma (2 cases, 5%), peripheral T-lymphoma, Hodgkin lymphoma, Ewing's sarcoma and germ cell tumor (1 case each). Pathological diagnosis was confirmed by bone marrow aspiration or thoracentesis in 14 cases, peripheral lymph node biopsy in 6 cases, and mediastinal biopsy in 22 cases. Twenty-seven cases (64%) had local anesthesia. Respiratory complications due to mediastinal mass developed in 3 of 15 cases who received general anesthesia. Of the 42 cases, 27 cases had sustained remission, 1 case survived with second-line therapy after recurrence, and 14 cases died (2 cases died of perioperative complications and 12 cases died of recurrence or progression of primary disease). The follow-up time was 36.7 (1.2, 76.1) months for 27 cases in continuous complete remission. The 3-year overall survival (OS) and events free survival (EFS) rates of 42 children were 59% (95%CI 44%-79%) and 58% (95%CI 44%-77%) respectively. Conclusions: SVCS associated with mediastinal malignancy in children is a life-threatening tumor emergency with high mortality. The most common primary disease is T-LBL. The most common clinical symptoms and signs are cough, wheezing, orthopnea and facial edema. Clinical management should be based on the premise of stable critical condition and confirm the pathological diagnosis through minimal invasive operation.
Child ; China ; Cough ; Edema ; Female ; Humans ; Male ; Mediastinal Neoplasms/diagnosis* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Respiratory Sounds ; Retrospective Studies ; Superior Vena Cava Syndrome/therapy*