Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications

This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.
Rats ; Animals ; Water ; Rats, Sprague-Dawley ; Liver ; NF-kappa B ; Liver Cirrhosis ; Bile Acids and Salts ; Body Weight ; RNA, Messenger

ObjectiveTo study the chemical structure of gardenia blue pigment and its inhibitory activity against monoamine oxidase B （MAO-B）， in order to seek a potential feasible way for rational utilization and value enhancement of iridoids in Gardeniae Fructus. MethodIridoid glycosides in Gardeniae Fructus were hydrolyzed by cellulase to obtain their aglycones and reacted with amino acids. Then， the products were purified by column chromatography packed with D101 macroporous resin and preparative liquid chromatography to obtain gardenia blue pigments， and the gardenia blue pigments were identified by nuclear magnetic resonance （NMR） and mass spectrometry （MS）. Benzylamine was used as the reaction substrate of MAO-B and in vitro incubated with gardenia blue pigment monomers， high performance liquid chromatography （HPLC） was employed to determine the production of benzaldehyde for evaluating the inhibitory effect of gardenia blue pigments on MAO-B， the mobile phase was methanol （A） -50 mmol·L^-1 potassium phosphate buffer （B， pH 3.2） （2∶3）， and the detection wavelength was 245 nm. ResultEight compounds of gardenia blue pigment A-H were synthesized and identified. In MAO-B inhibition test， compared with geniposide， the inhibitory activity of gardenia blue pigment D and E was significantly enhanced （P<0.05）. Compared with the 6β-hydroxygeniposide， the inhibitory activity of gardenia blue pigment G and H was significantly enhanced （P<0.05， P<0.01）. All the four gardenia blue pigments showed better MAO-B inhibitory activity than the prototype compounds. ConclusionGardenia blue pigment is a simple compound formed by one molecule of amino acid and one molecule of iridoid. Some gardenia blue pigments have better MAO-B inhibitory activity than the prototype compounds. The activity of gardenia blue pigment produced by different substrates is different， and the high-value gardenia blue pigment can be prepared based on experimental optimization， which can expand the application range of gardenia blue pigment and enrich the comprehensive utilization of iridoids from Gardeniae Fructus.

OBJECTIVE: This study aims to investigate the association of metabolic phenotypes that are jointly determined by body mass index (BMI) or fat mass percentage and metabolic health status with the ten-year risk of cardiovascular disease (CVD) among Chinese adults. METHODS: Data were obtained from a cross-sectional study. BMI and body fat mass percentage (FMP) combined with the metabolic status were used to define metabolic phenotypes. Multiple linear regression and logistic regression were used to examine the effects of metabolic phenotypes on CVD risk. RESULTS: A total of 13,239 adults aged 34-75 years were included in this study. Compared with the metabolically healthy non-obese (MHNO) phenotype, the metabolically unhealthy non-obese (MUNO) and metabolically unhealthy obese (MUO) phenotypes defined by BMI showed a higher CVD risk [odds ratio, OR (95% confidence interval, CI): 2.34 (1.89-2.89), 3.45 (2.50-4.75), respectively], after adjusting for the covariates. The MUNO and MUO phenotypes defined by FMP showed a higher CVD risk [ OR (95% CI): 2.31 (1.85-2.88), 2.63 (1.98-3.48), respectively] than the MHNO phenotype. The metabolically healthy obese phenotype, regardless of being defined by BMI or FMP, showed no CVD risk compared with the MHNO phenotype. CONCLUSION General obesity without central obesity does not increase CVD risk in metabolically healthy individuals. FMP might be a more meaningful factor for the evaluation of the association of obesity with CVD risk. Obesity and metabolic status have a synergistic effect on CVD risk.
Adipose Tissue/anatomy & histology* ; Adult ; Aged ; Body Mass Index ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Metabolic Diseases/etiology* ; Middle Aged ; Obesity/complications* ; Phenotype ; Regression Analysis ; Risk Factors

The surgical treatment of recurrent anterior shoulder dislocation is a difficult problem in the field of sports injury medicine. The main reason focus on dynamic and osseous constraints of shoulder joint could not recover well. At present, arthroscopic surgery is used at home and abroad, and could receive statisfied postoperative effect, but the choice of specific surgical methods is still controversial. According to presence and size of glenoid and humeral skull defects, different treatments should be selected in clinic. The author recommends that no articular glenoid defect or glenoid defect <20%, choose Bankart surgery;articular glenoid defect <20% with Hill-Sachs bone defect <40%, choose Bankart surgery combined with remplissage surgery or ASA surgery;Glenoid defect 20% to 25%, choose "Sling";Glenoid defect 25% to 40%, choose Bristow-Latarjet; Glenoid or Hill-Sachs bone defect>40% or Bristow-Latarjet if the surgical repair fails, bone grafting is used. In addition, if (humeral avulsion of glenohumeral ligaments, HAGL) injury existed, HAGL injury repair should be used. In addition to considering the important factor of bone defects, it is necessary to combine patient's age, exercise level and surgeon's technique to comprehensively select the bestsurgical method.
Arthroscopy ; Humans ; Joint Instability ; Recurrence ; Scapula ; Shoulder Dislocation/surgery* ; Shoulder Joint

Recurrent anterior dislocation of shoulder with bone defect is one of the common diseases of shoulder joint. How to effectively repair glenoid bone defect and reduce recurrence rate of shoulder dislocation is a problem that clinicians focus on. Bone grafting could stimulate bone, promote bone regeneration and bone remodeling, and restore the normal anatomical structure of glenoid. Among them, Bristow-Latarjet procedure is a classic operation for recurrent shoulder dislocation. Latarjet procedure could repair larger glenoid bone defects, but with higher surgical skills for surgeons;autogenous iliac grafting is the first choice for revision once Latarjet procedure failed;osteochondral grafting (autogenous and allogenous) has certain advantages in reconstructing original articular surface and preventing joint degeneration, but autologous osteochondral grafting may cause secondary injury, while immune rejection is difficult to avoid for allogenous osteochondral grafting. With the improvement of composite materials, and the mechanism of bone regeneration and remodeling, as well as the advantages and disadvantages of bone grafting, tissue engineering technology may become an effective method for the treatment of glenoid bone defect in the future.
Bone Transplantation ; Humans ; Joint Instability ; Recurrence ; Shoulder ; Shoulder Dislocation/surgery* ; Shoulder Joint

Objective:To observe the effect of modified Erchentang on the expression of CXC chemokine ligand (CXCL) 8-CXC chemotaxis factor receptor (CXCR) 1/2 genes in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the anti-inflammatory molecular mechanism of Erchentang on COPD. Method:Forty SD rats were randomly divided into normal group, model group, Jizhi syrup group and modified Erchentang group. COPD models in rats were prepared by cigarette smoke and dripping lipopolysaccharide (LPS) in the trachea. After modeling, normal and model groups were intragastrically given normal saline solution, Jizhi syrup group was given Jizhi syrup（10 g·kg^-1），and modified Erchentang group was given intragastrically corresponding herbal drugs (10 g·kg^-1) for 14 days. The levels of chemokines CXCL1, CXCL8 were detected by enzyme-linked immunosorbent assay in rat bronchoalveolar lavage fluid (BALF). The mRNA expressions of CXCL8, CXCR1 and CXCR2 were detected by quantitative real time PCR (Real-time PCR). Western blot was used to detect the levels of CXCL8, CXCR1 and CXCR2 protein, the pathological changes of lung tissues were observed by hematoxylin-eosin(HE) staining,and immunohistochemistry (IHC) method was used to detect the expressions of CXCL8, CXCR1 and CXCR2 protein in the lung tissue of all the groups. Result:The levels of chemokines CXCL1, CXCL8 in rats BALF were increased significantly (P<0.01), the expressions of CXCL8，CXCR1 and CXCR2 mRNA and protein were increased significantly (P<0.05, P<0.01) in model group compared with normal group. Compared with model group, the expressions of CXCL8, CXCR1 and CXCR2 mRNA and protein were decreased significantly (P<0.05), and the levels of chemokines CXCL1, CXCL8 in rats BALF were decreased significantly (P<0.01) in modified Erchentang. Conclusion:Modified Erchentang has an anti-inflammatory effect on COPD. The mechanism may be related to inhibiting the expressions of CXCL8, CXCR1, CXCR2 mRNA and protein, and reducing the release of chemokines CXCL1, CXCL8.