Objective To compare the long-term survival outcomes of patients with T_1-2N₀M₀ duodenal neuroendocrine tumor (DNET) after endoscopic resection (ER) or surgical resection (SR). Methods Patients diagnosed with T_1-2N₀M₀ DNET between January 1, 2004, and December 31, 2015, were extracted from the SEER database. Kaplan-Meier survival curve and log-rank test were used to compare overall survival (OS) rate and cancer-specific survival (CSS) rate between patients undergoing ER or SR. Propensity score matching (PSM) was used to reduce grouping differences, and multivariate Cox regression was used to analyze factors affecting OS and CSS before and after PSM. Results A total of 656 patients were included, with 457 in ER group and 199 in SR group. Before PSM, there was no significant difference in the 5-year OS rate between the ER and SR groups (88.9% vs 89.6%), but there was a significant difference in the 5-year CSS rate (99.3% vs 96.9%, P＝0.017). Before PSM, multivariate Cox regression analysis showed advanced age was an independent risk factor for decreased OS (P＜0.001). After PSM, there was no significant difference between the ER group (n＝187) and SR group (n＝187) in 5-year OS rate (90.2% vs 88.9%) or CSS rate (98.9% vs 96.7%). After PSM, multivariate Cox regression also showed advanced age was an independent risk factor for decreased OS, while resection method was not an independent factor for OS or CSS. Conclusions There is no significant difference in OS or CSS after endoscopic treatment and surgical treatments for patients with T_1-2N₀M₀ DNET, and advanced age is an independent factor for OS.

The study investigated the specific mechanism by which oxocrebanine, the anti-hepatic cancer active ingredient in Stephania hainanensis, inhibits the proliferation of hepatic cancer cells. Firstly, methyl thiazolyl tetrazolium(MTT) assay, 5-bromodeoxyuridine(BrdU) labeling, and colony formation assay were employed to investigate whether oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells. Propidium iodide(PI) staining was used to observe the oxocrebanine-induced apoptosis of HepG2 and Hep3B2.1-7 cells. Western blot was employed to verify whether apoptotic effector proteins, such as cleaved cysteinyl aspartate-specific protease 3(c-caspase-3), poly(ADP-ribose) polymerase 1(PARP1), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Bcl-2 homologous killer(Bak), and myeloid cell leukemia-1(Mcl-1) were involved in apoptosis. Secondly, HepG2 cells were simultaneously treated with oxocrebanine and the autophagy inhibitor 3-methyladenine(3-MA), and the changes in the autophagy marker LC3 and autophagy-related proteins [eukaryotic translation initiation factor 4E-binding protein 1(4EBP1), phosphorylated 4EBP1(p-4EBP1), 70-kDa ribosomal protein S6 kinase(P70S6K), and phosphorylated P70S6K(p-P70S6K)] were determined. The results of MTT assay, BrdU labeling, and colony formation assay showed that oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells in a dose-dependent manner. The results of flow cytometry suggested that the apoptosis rate of HepG2 and Hep3B2.1-7 cells increased after treatment with oxocrebanine. Western blot results showed that the protein levels of c-caspase-3, Bax, and Bak were up-regulated and those of PARP1, Bcl-2, and Mcl-1 were down-regulated in the HepG2 cells treated with oxocrebanine. The results indicated that oxocrebanine induced apoptosis, thereby inhibiting the proliferation of hepatic cancer cells. The inhibition of HepG2 cell proliferation by oxocrebanine may be related to the induction of protective autophagy in hepatocellular carcinoma cells. Oxocrebanine still promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, reduced the phosphorylation levels of 4EBP1 and P70S6K, which can be reversed by the autophagy inhibitor 3-MA. It is prompted that oxocrebanine can inhibit the proliferation of hepatic cancer cells by inducing autophagy. In conclusion, oxocrebanine inhibits the proliferation of hepatic cancer cells by inducing apoptosis and autophagy.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Cell Proliferation/drug effects* ; Hep G2 Cells ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Caspase 3/genetics*

Traditional Chinese medicine(TCM) is the pillar for the development of motherland medicine, and animal medicine has a long history of application in China, characterized by wide resources, strong activity, definite efficacy, and great benefits. It has significant potential and important status in the consumption market of raw materials of TCM. In the context of global climate change, farming system alterations, and low renewability, the depletion of wild medicinal animal resources has accelerated. Accordingly, the conservation and sustainable utilization of wild resources of animal medicinal materials has become a problem that garners increasing attention and urgently needs to be solved. This paper summarizes the current situation of domestic and foreign medicinal animal breeding and research progress in industrial application in recent years and points out the issues related to standardized breeding, germplasm selection and breeding, and quality evaluation standards for medicinal animals. Furthermore, this paper discusses standardized breeding, quality standards, resource protection and utilization, and the search for alternative resources for rare and endangered medicinal animals. It proposes that researchers should systematically carry out in-depth basic research on animal medicine, improve the breeding scale and level of medicinal animals, employ modern technology to enhance the quality standards of medicinal materials, and strengthen the research and development of alternative resources. This approach aims to effectively address the relationship between protection and utilization and make a significant contribution to the sustainable development of medicinal animal resources and the animal-based Chinese medicinal material industry.
Animals ; Breeding ; China ; Medicine, Chinese Traditional ; Conservation of Natural Resources

OBJECTIVE: To evaluate the efficacy and safety of PD-1 inhibitor combined with azacitidine and HAG regimen in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: This study is a prospective, single-arm, phase II clinical trial that included R/R AML patients who met the inclusion criteria and were treated at The First Affiliated Hospital of Soochow University from December 2020 to August 2023. Patients could undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) after salvage therapy. The efficacy and safety were evaluated. RESULTS: Twenty patients were enrolled, including 14 males and 6 females, with an average age of (50.7±15.3) years. The overall response rate (ORR) after one cycle of the treatment was 75.0% (15/20), and 35.0% (7/20) of the patients achieved complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after two cycles of the treatment. Eight patients received allo-HSCT. The main adverse events were hematologic toxicities, and no grade 5 adverse events occurred. CONCLUSION The combination of PD-1 inhibitor, azacitidine, and the HAG regimen is a feasible and relatively safe treatment option for R/R AML, thus, to be worth further study.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Azacitidine/administration & dosage* ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; Hematopoietic Stem Cell Transplantation ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Aged

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective To explore the metastasis rate and related risk factors of T1 stage colonic neuroendocrine tumor(C-NET),and to compare the long-term survival outcomes of patients with non-metastatic(T1N0M0 stage)C-NET after local excision(LE)or radical surgery(RS).Methods Clinical information of 433 patients diagnosed with C-NET in the SEER database from January 1,2004 to December 31,2015 were analyzed.Cox regression was used to analyze the influencing factors of metastasis of C-NET.The patients without metastasis were divided into LE group and RS group,and assigned in a 1∶1 ratio using propensity score matching(PSM)according to gender,age,tumor largest diameter,and infiltration depth,with a caliper value set to 0.02.Kaplan-Meier survival curve was used to analyze 5-year cancer-specific survival(CSS)and overall survival(OS)of patients.Cox regression analysis was used to evaluate the influence of metastasis on survival.Results Among 419 C-NET patients,19(4.52%)had distant metastases.Cox regression analysis showed that 11-20 mm of tumor large diameter(HR=9.264,95%CI 3.322-25.835,P＜0.001),right colon location(HR=0.116,95%CI 0.042-0.321,P＜0.001),and submucosal invasion(HR=5.842,95%CI 1.858-18.371,P=0.003)were independent risk factors for distant metastasis of T1 stage C-NET.The 5-year OS rates of non-metastatic and metastatic patients were 94.5%and 47.4%,respectively(χ2=79.762,P＜0.001),and their 5-year CSS rates were 99.5%and 55.7%,respectively(χ2=164.604,P＜0.001).Before PSM,the 5-year OS rates of non-metastatic C-NET patients after LE and RS were 95.8%and 90.1%(χ2=2.679,P=0.063),and the 5-year CSS rates were 100.0%and 97.2%(χ2=0.579,P=0.038);after PSM,the 5-year OS rates of non-metastatic patients after LE and RS were 96.8%and 92.1%(χ2=3.606,P=0.058),and the 5-year CSS rates were 100.0%and 98.5%(χ2=1.015,P=0.314).After PSM,there was no significant difference in the 5-year OS and CSS of patients with defferent tumor location,tumor large diameter,or submucosal invasion between the LE and RS groups.Conclusions 11-20 mm of tumor diameter,right colon location,and submucosal invasion might be independent risk factors for distant metastasis of T1 stage C-NET,and LE could be an appropriate treatment option for non-metastatic C-NET.

Objective To investigate the effect of astragaloside Ⅳ on high glucose-induced pyroptosis and invasive migration of human chorionic trophoblast cells(HTR-8/SVneo).Methods HTR-8/SVneo cells were divided into 4 groups:control group(untreated),high glucose group(high glucose stimulation)and astragaloside Ⅳ 50 and 100 μmol/L group(high glucose stimulation + astragaloside).Cell activity was detected by Cell Counting Kit 8(CCK-8),cell invasion and migration abilities were determined by Transwell assay and scratch assay,respectively,cell pyroptosis was assessed by Hoechst 33342/propidium iodide(PI)dual fluorescence staining.The protein expression levels of NOD-like receptor thermoprotein structural domain(NLRP3),cleaved-Caspase-1,GSDMD-NT,and IL-18 were detected by Western Blot.Results Compared with the control group,HTR-8/SVneo cell viability was significantly reduced in the high glucose group,the rate of cell migration was significantly reduced,the number of invasive cells was significantly reduced,the percentage of PI-positive cells was significantly increased,and the levels of NLRP3,cleaved-Caspase-1,GSDMD-NT and IL-18 protein expression levels were significantly increased(P<0.05 or P<0.01);compared with the high glucose group,cell viability was significantly higher in the astragaloside Ⅳ treated group,the rate of cell migration was significantly increased,the number of invasive cells was significantly increased,the percentage of PI-positive cells was significantly decreased,and the protein expressions of number of NLRP3,cleaved-Caspase-1,GSDMD-NT,IL-18 were significantly decreased(P<0.05 or P<0.01).Conclusion AstragalosideⅣcan inhibit high glucose-induced HTR-8/SVneo cell pyrolysis and improve cell invasion and migration ability.

Objective:To explore effect of IgG receptor FcγRⅡB on neuronal injury and imbalance of Th17/Treg in experi-mental autoimmune encephalomyelitis(EAE)model mice.Methods:C57BL/6 mice were randomly divided into control group,EAE group,FcγRⅡB group and EAE+FcγRⅡB group,with 15 mice in each group.EAE model was induced by subcutaneous injection of MOG35-55 peptide and treated with FcγRⅡB lentiviral solution.After modeling was established,body weight of mice was weighed every day,and neurological function was scored for 30 d;after 30 days,mice were sacrificed.HE staining was used to observe patho-logical changes of brain tissue,LFB staining was used to assess structural changes of spinal cord myelin,and immunofluorescence staining was used to detect spinal cord cerebral cortex neuron nuclear antigen(NeuN)and Caspase-3 expressions,TUNEL staining was used to detect apoptosis of neurons,ELISA was used to detect serum IL-6,IL-17,IL-10 and TGF-β levels,flow cytometry was used to analyze proportion of Th17 and Treg cells in spleen,Western blot was used to determine protein expressions of retinoic acid-related orphan receptor γt(RORγt)and Forkhead family transcription factor 3(Foxp3)in spinal cord tissue.Results:Compared with control group,mice in EAE group had decreased body weight,increased neurological function scores,obvious infiltration of inflamma-tory cells in brain tissue,and signs of demyelination in spinal cord,fluorescence expression intensity of NeuN was weakened and fluorescence expression intensity of Caspase-3 was enhanced,there were more TUNEL-positive stained cells,number of apoptotic cells was increased,levels of IL-6 and IL-17 in serum were increased,and levels of IL-10 and TGF-β were decreased,proportion of Th17 cells in spleen was increased,proportion of Treg was decreased,expression of RORγt protein in spinal cord tissue was up-regu-lated while relative expression of Foxp3 protein was down-regulated(P<0.05);compared with EAE group,weight of mice in EAE+FcγRⅡB group was increased,neurological function score was decreased,infiltration of inflammatory cells in brain tissue was reduced,demyelination of spinal cord was improved,fluorescence expression intensity of NeuN was enhanced,and fluorescence expression intensity of Caspase-3 was weakened,there were fewer TUNEL-positive stained cells,number of apoptotic cells was decreased,levels of IL-6 and IL-17 in serum were decreased,while levels of IL-10 and TGF-β were increased,at the same time,proportion of Th17 cells in spleen was decreased and proportion of Treg was increased,expression of RORγt protein in spinal cord tissue was down-regulated,while expression of Foxp3 protein was up-regulated(P<0.05).Conclusion:FcγRⅡB has neuroprotective effect on EAE mice,and can reduce infiltration of inflammatory cells and demyelination in brain tissue,whose mechanism may be related to regulation of cytokine levels and immune balance of Th17/Treg cells.

Objective:To investigate the effect of glucocorticoids on brain injury in rats with Streptococcus pneumoniae(SP)meningitis,as well as the changes of cerebrospinal fluid immunoglobulin levels under this effect.Methods:A total of 40 SD rats were divided into control group,model group,low-dose methylprednisolone sodium succinate group(Low-MSS)and high-dose methylpred-nisolone sodium succinate group(High-MSS)according to random table method,with 10 rats in each group.Except for the control group,SP meningitis models were established in other groups.Rats in Low-MSS group and High-MSS group were injected with methyl-prednisolone sodium succinate by tail vein at doses of 5 mg/kg and 10 mg/kg,respectively,once a day for 21 days.Neurobehavioral scores of rats after modeling were performed by Loeffler method;contents of immunoglobulin IgA,IgM and IgG in cerebrospinal fluid of rats were detected by immunoturbidimetry;levels of inflammatory cytokines TNF-α,IL-6 and IFN-γ in supernatant of rats brain ho-mogenate were determined by ELISA;HE staining was used to detect pathological changes of rats brain tissue;Nissl staining was used to detect the number of neuronal cells in rats brain tissue;TUNEL staining was used to detect the number of apoptotic cells in rats brain tissue;immunofluorescence staining was used to detect expressions of GFAP and S-100b,the marker proteins of rat brain tissue injury.Results:Before SP injection,there was no difference in neurobehavioral scores between control group and model group(P>0.05),at 24 h,48 h and 72 h after SP injection,neurobehavioral scores in model group were significantly lower than those in control group(P<0.05).Compared with control group,contents of IgA,IgM and IgG in cerebrospinal fluid of rats in model group were in-creased,and contents of TNF-α,IL-6 and IFN-γ in supernatant of the brain homogenate were also increased,the tissue was obviously damaged,accompanied by a large number of inflammatory cells infiltration,the number of neuronal cells were decreased,the number of apoptotic cells were increased,and the fluorescence density values of S-100b and GFAP were increased(P<0.05);compared with model group,contents of IgA,IgM and IgG in cerebrospinal fluid of rats in Low-MSS group and High-MSS group were decreased,and contents of TNF-α,IL-6 and IFN-γ in brain homogenate supernatant were also decreased(P<0.05),brain tissue damage was alleviated,inflammatory cell infiltration was significantly reduced,neuronal cells were increased,the number of apoptotic cells were decreased,and the fluorescence density values of S-100b and GFAP were also decreased(P<0.05).In addition,the improvement effect of various indexes and brain tissue damage in High-MSS group was better than that in Low-MSS group,and the difference were statistically signifi-cant(P<0.05).Conclusion:Glucocorticoid methylprednisolone sodium succinate can effectively improve the brain tissue damage in SP meningitis rats,regulate the levels of immunoglobulin IgA,IgM and IgG,and has a protective effect on SP meningitis rats.

Chlamydia psittaci is a worldwide distributed zoonotic pathogen that infects a variety of birds.In order to char-acterization of the duck originated C.psittaci strains,lung samples were collected from suspected infection ducks and was de-tected by real-time PCR.The positive samples were homogenized in phosphate buffered saline with kanamycin and streptomy-cin,and then inoculated onto L929 cells monolayer.After several sets of passages,chlamydial inclusions of the isolate in cul-tured cells were observed after Giemsa staining or by electron microscope.For species identification,16S rRNA,16-23S IGS gene fragments were sequenced and analyzed.Genotyping of the isolate was performed by comparative analysis of the obtained ompA gene sequence with that of different genotype of C.psittaci strains.A C.psittaci strain was successfully isolated from the lung sample of duck by cell culture and was identified as genotype A.This study expanded our understanding of the host range of genotype A C.psittaci strain,and provided basis for further research on the pathogenicity,transmission,and public health risk of this pathogen.