OBJECTIVE: To explore the construction method of a resistant multiple myeloma (MM) patient-derived xenotransplantation (PDX) model. METHODS: 1.0×10⁷ MM patient-derived mononuclear cells (MNCs), 2.0×10⁶ MM.1S cells and 2.0×10⁶ NCI-H929 cells were respectively subcutaneously inoculated into NOD.CB17-Prkdc^scid Il2rg^tm1/Bcgen (B-NDG) mice with a volume of 100 μl per mouse to establish mouse model. The morphologic, phenotypic, proliferative and genetic characteristics of PDX tumor were studied by hematoxylin-eosin staining, immunohistochemical staining (IHC), cell cycle analysis, flow cytometry and fluorescence in situ hybridization (FISH). The sensitivity of PDX tumor to bortezomib and anlotinib monotherapy or in combination was investigated through cell proliferation, apoptosis and in vitro and in vivo experiments. The effects of anlotinib therapy on tumor blood vessel and cell apoptosis were analyzed by IHC, TUNEL staining and confocal fluorescence microscope. RESULTS: MM PDX model was successfully established by subcutaneously inoculating primary MNCs. The morphologic features of tumor cells from MM PDX model were similar to those of mature plasma cells. MM PDX tumor cells positively expressed CD138 and CD38, which presented 1q21 amplification, deletion of Rb1 and IgH rearrangement, and had a lower proliferative activity than MM cell lines. in vitro, PDX, MM.1S and NCI-H929 cells were treated by bortezomib and anlotinib for 24 hours, respectively. Cell viability assay showed that the IC₅₀ value of bortezomib were 5 716.486, 1.025 and 2.775 nmol/L, and IC₅₀ value of anlotinib were 5 5107.337, 0.706 and 5.13 μmol/L, respectively. Anlotinib treatment increased the apoptosis of MM.1S cells (P < 0.01), but did not affect PDX tumor cells (P >0.05). in vivo, there was no significant difference in PDX tumor growth between bortezomib monotherapy group and control group (P >0.05), while both anlotinib monotherapy and anlotinib combined with bortezomib effectively inhibited PDX tumor growth (both P < 0.05). The vascular perfusion and vascular density of PDX tumor were decreased in anlotinib treatment group (both P < 0.01). The apoptotic cells in anlotinib treatment group were increased compared with those in control group (P < 0.05). CONCLUSION Bortezomib-resistant MM PDX model can be successfully established by subcutaneous inoculation of MNCs from MM patients in B-NDG mice. This PDX model, which retains the basic biological characteristics of MM cells, can be used to study the novel therapies.
Animals ; Bortezomib ; Humans ; Multiple Myeloma/pathology* ; Mice ; Apoptosis ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Mice, Inbred NOD ; Disease Models, Animal ; Cell Proliferation ; Transplantation, Heterologous

OBJECTIVE: To investigate the clinical features and prognostic factors of primary tonsil lymphoma (PTL). METHODS: The clinical data of 41 patients diagnosed with PTL and treated in the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2022 were collected and retrospectively analyzed. Their clinical features and prognostic factors were analyzed. RESULTS: All the 41 patients were newly diagnosed with PTL, and the median age of onset was 58(19-85) years. Among them, 19 patients started with pharyngeal pain, 12 patients presented with dysphagia, 8 patients presented with pharyngeal mass, and 2 patients presented with blurred articulation. The most common pathological type was diffuse large B-cell lymphoma (24 cases, 58.54%). All patients received chemotherapy, and 3 patients were combined with hematopoietic stem cell transplantation. Among 41 patients, 11 (26.83%) achieved complete response, 14 (34.15%) achieved partial response, and the total response rate was 60.98% (25/41). The median follow-up time was 37(6-107) months, the 5-year overall survival (OS) rate was 70.81% and 5-year progression-free survival (PFS) rate was 66.20%. Univariate analysis showed that B symptoms, Ki-67, β₂-MG and IPI score had significant effects on PFS and OS of patients (all P < 0.05). Multivariate analysis showed that IPI score was an independent risk factor for PFS and OS of patients (P < 0.05). CONCLUSION The clinical manifestations of PTL lack specificity, and the prognosis is relatively good. Most patients can achieve long-term survival after treatment. IPI score is related to the prognosis.
Tonsillar Neoplasms/pathology* ; Lymphoma/pathology* ; Humans ; Prognosis ; Retrospective Studies ; Drug Therapy ; Progression-Free Survival ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Lymphoma, B-Cell/pathology* ; Survival Rate

Mesenchymal stem cells (MSCs) are an effective therapeutic strategy to delay aging in dogs, they are prone to aging and have poor genetic stability when cultured for a long time in vitro. Therefore, it is of great significance to explore a method to improve the anti-aging ability of MSCs. Previous studies have shown that sirtuin 6 (SIRT6) plays an important role in anti-aging. This study constructed MSCs with overexpressed SIRT6 gene. Through Giemsa staining and senescence-associated β-galactosidase staining, it was found that SIRT6 significantly enhances the anti-aging capacity of MSCs. Transmission electron microscopy imaging and the detection of oxidative stress-related indicators revealed that SIRT6 improves the anti-aging capacity of MSCs by maintaining mitochondrial homeostasis and reducing oxidative stress levels. Transcriptome sequencing analysis revealed that SIRT6 mainly acted on phosphatidylinositol-3-kinase, mitogen-activated protein kinase and other aging and inflammation related pathways. In the establishment and verification of aging models in mice and dogs, it was found that the spatial memory ability of the model mice was significantly increased after intravenous transplantation of SIRT6 overexpression cells, the organ index was also significantly changed, and the anti-oxidative capacity of the dogs and mice blood was improved. The morphology of the spleens and livers in the SIRT6 overexpression cell treatment group could be effectively restored, and the expression levels of aging and inflammation-related proteins were significantly decreased. This study provides a new idea for the study of SIRT6-mediated anti-aging of MSCs.
Animals ; Dogs ; Mesenchymal Stem Cells/metabolism* ; Sirtuins/genetics* ; Aging/physiology* ; Mice ; Oxidative Stress ; Mesenchymal Stem Cell Transplantation

Objective To explore the effect of kidney-warming and collateral-unblocking therapy on renal fibrosis in patients with diabetic nephropathy(DN)of kidney-yang deficiency type based on the theory of cold inducing contraction.Methods A retrospective study was conducted in 116 patients with DN of kidney-yang deficiency type who were admitted to Xi'an Jiaotong University Hospital from December 2020 to December 2022 by convenient sampling method.According to the treatment methods,the patients were divided into observation group and control group,with 58 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with the decoction of Wenshen Tongluo Prescription orally on the basis treatment for the control group.The course of treatment covered 8 weeks.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,blood glucose indicators of fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c)and 2-hour postprandial blood glucose(2hPG),renal fibrosis indicators of type Ⅳ collagen(Ⅳ-C),type Ⅲ procollagen(PC Ⅲ),hyaluronic acid(HA)and laminin(LN),serum inflammatory factor indicators of tumor necrosis factor α(TNF-α),hypersensitive C-reactive protein(hs-CRP)and interleukin 1β(IL-1β),and renal function indicators of serum creatinine(Scr)and blood urea nitrogen(BUN),and 24-hour urinary protein quantification(24h Upro).After treatment,the clinical efficacy and total incidence of adverse reactions were compared between the two groups.Results(1)After 8 weeks of treatment,the total effective rate of the observation group was 94.83％(55/58),and that of the control group was 75.86％(44/58).The intergroup comparison(tested by chi-square test)showed that the curative effect of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the scores of TCM symptoms of soreness and coldness of waist and knees,limb edema,fatigue and aversion to cold,and nocturnal polyuria in the two groups were lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of blood glucose indicators of FPG,HbA1c and 2hPG in the two groups were lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the serum levels of renal fibrosis indicators of Ⅳ-C,PC Ⅲ,HA and LN in the two groups were lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the serum levels of inflammatory factors of TNF-α,hs-CRP and IL-1β in the two groups were decreased when compared with those before treatment(P＜0.05),and the decrease in the observation group was more significant than that in the control group(P＜0.01).(6)After treatment,the serum levels of renal function indicators of Scr,BUN and 24h Upro in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(7)The total incidence of adverse reactions in the observation group was 3.45％(2/58),and that in the control group was 8.62％(5/58).There was no significant difference between the two groups(P＞0.05).Conclusion Wenshen Tongluo Prescription formulated according to the theory of cold inducing contraction can effectively alleviate the symptoms such as soreness and coldness of waist and knees in DN patients with kidney-yang deficiency syndrome,improve renal fibrosis and renal function,decrease blood glucose level,and alleviate the inflammatory response.During the treatment period,there are no serious adverse reactions occurring in the patients,indicating that the therapy is safe and effective.

Objective To compare the diagnostic value of ultrasonography and CT in acute appendicitis.Methods A retrospective analysis was conducted on 279 patients who were diagnosed with acute appendicitis and followed emergency surgery.Patients were divided into different subgroups based on postoperative pathological results and body mass index(BMI),and the pathological results were used as the gold standard to analyze whether there were differences in the diagnostic accuracy of ultrasonography and CT examination for acute appendicitis.Results A total of 279 patients with confirmed acute appendicitis,with 64 cases of simple appendicitis,127 cases of suppurative appendicitis,and 88 cases of gangrenous appendicitis according to pathological classification.The diagnostic accuracy of ultrasonography was 68.75%(44/64),73.22%(93/127),and 81.81%(72/88),respectively.The diagnostic accuracy of CT was 71.87%(46/64),82.67%(105/127),and 90.90%(80/88),respectively.There was no statistically significant difference in diagnostic accuracy between the two examinations(P>0.05).Subgroup analysis based on patient BMI showed that there was no difference in diagnostic accuracy of the two examinations for patients with normal BMI(P>0.05),while for overweight and obese patients,the diagnostic accuracy of CT was better than that of ultrasonography,with a statistical difference(P<0.05).Conclusion There is no difference in the diagnostic accuracy of ultrasonography and CT examinations for acute appendicitis of different pathological types.But for overweight and obese acute appendicitis patients,the diagnostic accuracy of CT examination is superior to ultrasonography.

Sulforaphane is a naturally occurring active substance derived from cruciferous vegetables with potent antioxidant and anticancer properties. Researches have shown that sulforaphane has good bioavailability and can be absorbed by the small intestine through passive transport, followed by excretion in the form of urine via the hydrophobic acid pathway. In addition, since sulforaphane is easy to be absorbed and metabolized, wrapping sulforaphane with nanomaterials can improve its bioavailability and stability, prolong its action time in human body, and better utilize its therapeutic effect. In terms of mechanism of action, sulforaphane can activate Nrf2 and HSF1 signaling pathways, induce the expression of phase II detoxification enzymes HO-1, NADPH, GST and HSP, thus regulating the concentration of oxidative stress ROS in vivo; inhibit NF-κB signaling pathway, thus suppressing the expression of inflammatory factors TNF-α, IL-1 and IL-6; regulate epigenetic modifications, thus inhibiting HDAC and DNMT, and increasing the concentration of histone H3 and H4. By regulating the expression levels of the above factors, sulforaphane can affect the occurrence and development of cancer, neurodegenerative diseases and other diseases. In recent years, several phase I/II clinical trials have shown that sulforaphane has good drug-generating properties. For example, researchers have found that patients with skin cancer have not shown any health problems and their corresponding functional problems have improved greatly after long-term use of sulforaphane. This suggests that in the future sulforaphane has a very high medicinal potential for the treatment of cancer and neurodegenerative diseases. In this paper, we review the pharmacokinetics, target of action and safety of sulforaphane and its research progress in tumor and neurodegenerative diseases to provide a reference for the future application of sulforaphane in the treatment of tumor and neurodegenerative diseases.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

Targeted regulation of hypoxia inducible factor(HIF)pathway can provide therapeutic basis for inflammatory anemia,hypoxic nephropathy,cardiovascular diseases related to chronic kidney disease and other hypoxic diseases.At present,the first drug to act on the HIF pathway,roxadustat,has been used for the treatment of renal anemia,and other prolyl hydroxylase(PHD)inhibitors are also in clinical research.This article mainly reviews the various pathways and mechanisms of the protective effect of PHD inhibitors on the kidneys.

Refractory depression is a drug-resistant subtype of major depressive disorder for which there is a lack of effective and durable treatments.Seroxibine,the active substance in the mushroom Capsicum annuum,is a natural 5-hydroxytryptamine hallucinogen that activates the 5-hydroxytryptamine 2A receptor to mediate multiple aspects of antidepressant effects.In recent years,it has received renewed attention for its outstanding therapeutic effects in the treatment of refractory depression or other psychiatric disorders.Therefore,this paper summarizes the studies on neuroplasticity,brain neural connectivity network,neurotransmitters,immune factors,microbiota-gut-brain axis,and clinical efficacy of seloxipine in domestic and international literature,and explores the possible mechanisms of seloxipine's effect on refractory depression,with a view to providing theoretical basis for the clinical application of this drug.