OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Child, Preschool ; Combined Modality Therapy ; Humans ; Infant ; Neuroblastoma/drug therapy* ; Positron-Emission Tomography ; Radionuclide Imaging ; Retrospective Studies ; Treatment Outcome

Hemophagocytic syndrome (HPS) is a severe disease characterized by excessive release of inflammatory cytokines caused by abnormal activation of lymphocytes and macrophages, which can cause multiple organ damage and even death. Panniculitis is a disease characterized by inflammation of subcutaneous adipose tissue. We effectively treated 2 patients with panniculitis-associated HPS with ruxolitinib. Case 1: A 70-year-old male started with intermittent plantar swelling and pain, and then developed leukocytosis, mild anemia, multiple red maculopapules with painless subcutaneous nodules on the forehead, neck and bilateral lower legs. The patient was treated with prednisone and leflunomide for improvement. After that, repeated fever and rash occurred again. After admission to our hospital, we found his leukocyte and hemoglobin decreased, ferritin raised, fibrinogen and natural killer (NK) cell activity decreased, and hemophagocytic cells were found in bone marrow aspiration. The skin pathology was consistent with non-suppurative nodular panniculitis. He was diagnosed with nodular panniculitis associa-ted HPS. He was treated with glucocorticoid, cyclosporine, etoposide and gamma globule, but the disease was not completely controlled. After adjusting etoposide to ruxolitinib, his symptoms and abnormal laboratory findings returned to normal. After 2 months he stopped using ruxolitinib due to repeated infections. During the follow-up, though the prednisone dose was tapered, his condition was stable. Case 2: A 46-year-old female patient developed from intermittent fever, erythematous nodular rash with tenderness, leukopenia, and abnormal liver function. antibiotic therapy was ineffective. She improved after glucocorticoid treatment, and relapsed after glucocorticoid reduction. There were fever, limb nodules, erythema with ulcerative necrosis, intermittent abdominal pain when she came to our hospital. Blood examination showed that her white blood cells, red blood cells and platelets were decreased, fibrinogen was decreased, triglyceride was increased, ferritin and soluble interleukin-2 receptor(SIL-2R/sCD25) were significantly raised, and hemophagocytic cells were found in bone marrow aspiration. It was found that Epstein-Barr virus DNA was transiently positive, skin Staphylococcus aureus infection, and pulmonary Aspergillus flavus infection, but C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were normal, and no evidence of tumor and other infection was found. Skin pathology was considered panniculitis. The diagnosis was panniculitis, HPS and complicated infection. Antibiotic therapy and symptomatic blood transfusion were given first, but the disease was not controlled. Later, dexamethasone was given, and the condition improved, but the disease recurred after reducing the dose of dexamethasone. Due to the combination of multiple infections, the application of etoposide had a high risk of infection spread. Ruxolitinib, dexamethasone, and anti-infective therapy were given, and her condition remained stable after dexamethasone withdrawal. After 2 months of medication, she stopped using ruxolitinib. One week after stopping using ruxolitinib, she developed fever and died after 2 weeks of antibiotic therapy treatment in a local hospital. In conclusion, panniculitis and HPS are related in etiology, pathogenic mechanism and clinical manifestations. Abnormal activation of Janus-kinase and signal transduction activator of transcription pathway and abnormal release of inflammatory factors play an important role in the pathogenesis of the two diseases. The report suggests that ruxolitinib is effective and has broad prospects in the treatment of panniculitis associated HPS.
Humans ; Male ; Female ; Middle Aged ; Aged ; Lymphohistiocytosis, Hemophagocytic/drug therapy* ; Glucocorticoids/therapeutic use* ; Epstein-Barr Virus Infections/complications* ; Etoposide/therapeutic use* ; Prednisone/therapeutic use* ; Herpesvirus 4, Human ; Panniculitis/complications* ; Dexamethasone/therapeutic use* ; Exanthema/complications* ; Ferritins/therapeutic use* ; Anti-Bacterial Agents/therapeutic use* ; Fibrinogen/therapeutic use*

ObjectiveTo investigate the diagnostic efficiency of noninvasive preimplantation genetic testing for aneuploidy （niPGT-A）. MethodsA total of 24 blastocysts diagnosed as aneuploid or mosaic by initial trophectoderm biopsy （TE1） preimplantation genetic testing for aneuploidy （PGT-A） were donated by 11 couples with reciprocal translocation or Robertsonian translocation. All the PGT cycles were performed at Center for Reproductive Medicine in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2018 to July 2019. The 24 frozen-thawed blastocysts were reanalyzed by trophectoderm re-biopsy （TE2）， inner cell mass （ICM） biopsy and collection of spent blastocyst culture medium/blastocoel fluid （BCM/BF） using Next Generation Sequencing （NGS） platform. With the corresponding ICM result as the actual chromosomal status， the karyotype concordances with corresponding ICM were compared among TE1， TE2 and BCM/BF sampling. ResultsThe karyotype concordance rates of TE1， TE2 and BCM/BF with their corresponding ICM were 66.7%， 87.5% and 79.2%， respectively （P>0.05）. No statistically significant difference was found between any two groups （P>0.05）. ConclusionsniPGT-A by using BCM/BF could achieve similar diagnostic efficiency as TE2-biopsy PGT-A and ICM-biopsy PGT-A.

Air Pollution ; Asthma/drug therapy* ; China ; Humans ; Treatment Adherence and Compliance

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Five alkaloids were isolated from a decoction of Uncaria rhynchophylla by a combination of various chromatographic techniques, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and reversed phase HPLC. Their structures were characterized by comprehensive analyses of spectroscopic data as monoterpene indole alkaloids (+)-(7R)-3-oxo-7-hydroxy-3,7-seco-dihydrorhynchohylline (1), (+)-(7S)-3-oxo-7-hydroxy-3,7-seco-dihydrorhyncho-hylline (2), (+)-(7R)-3-oxo-7-hydroxy-3,7-seco-rhynchohylline (3) and (+)-(7S)-3-oxo-7-hydroxy-3,7-seco-rhynchohylline (4), and a β-carboline alkaloid 1,2,3,4-tetrahydro-1-oxo-β-carboline (5). Among them, 1 and 2 are new compounds, 3 and 4 are new natural products that were semi-synthesized from isorhynchohylline with incorrect specific rotations, and 5 is isolated for the first time from the genus Uncaria.

ObjectiveTo investigate the role of the serum inhibin B (INHB) level in evaluating the testicular function of the prepubertal patient with varicocele (VC) after high ligation of the spermatic vein (HLSV).

METHODSThis study included 31 prepubertal male patients with left VC, averaging 12.55 years of age and 9 complicated by right VC. We collected peripheral blood samples before and at 4, 12 and 26 weeks after HLSV as well as spermatic venous blood samples intraoperatively for determination of the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-sperm antibody (AsAb) and serum INHB by ELISA.

RESULTSCompared with the baseline, statistically significant differences were observed in the INHB level in the peripheral blood at 12 and 26 weeks after operation (［255.18 ± 69.97］ vs ［141.78 ± 59.82］ pg/ml, P < 0.05) and that in the spermatic venous blood intraoperatively (［255.18 ± 69.97］ vs ［412.44 ± 259.42］ pg/ml, P < 0.01). Spearman's analysis showed a negative correlation between the level of INHB and that of FSH (r = －0.224, P < 0.01).

CONCLUSIONSThe level of serum INHB in the peripheral blood of the prepubertal VC patient is decreased within 6 months after HLSV and negatively correlated with that of FSH. The levels of INHB and FSH may well reflect the testicular function of the prepubertal VC patient.

Adolescent ; Antibodies ; blood ; Biomarkers ; blood ; Child ; Follicle Stimulating Hormone ; blood ; Humans ; Inhibins ; blood ; Luteinizing Hormone ; blood ; Male ; Spermatozoa ; immunology ; Testosterone ; blood ; Varicocele ; blood

Objective To study the anti thrombotic effect of Ligustrazine injection combined with aspirin,clopidogrel in rabbits.Methods Forty-two healthy Japanese white rabbits were randomly divided into 7 groups:blank group,control A group,control B group,control-low dose herb group,control-high dose herb group,combined A group,combined B group.Blank group was given equal volume normal saline,control A group was given aspirin 5.13 mg· kg-1,control B group was given clopidogrel 3.85 mg · kg-1,control-low,high doses herb groups were given Ligustrazine injection 6.54,26.16 mg · kg-1,combined A group was given Ligustrazine injection 26.16 mg· kg-1 and aspirin 5.13 mg · kg-1,combined B group was given Ligustrazine injection 26.16 mg · kg-1 and clopidogrel 3.85 mg · kg-1.Ligustrazine injection was given for ten days through ear marginal vein and aspirin,clopidogrel were given for seven days through intragastric administration.On the last day of administration,heart blood was taken at 1 h after administration.Thrombus length and wet weight were measured by extracorporeal thrombus forming apparatus.The effect on the platelet aggregation rate induced by platelet activating factors (PAF) was measured by platelet aggregation instrument.And the content of platelet activating factors (PAF),cluster of differentiation 62 platelet (CD62p) and platelet factor-4 (PF-4) were detected by enzyme-linked immunosorbent assay.Results The throrobus length in combined B group was (7.4 ± 4.6) cm,which significantly reduced compared with that of blank group (22.8 ±2.3) cm (P ＜0.01).The wet weights of thrombus of control A,B group,control-high dose herb group and combined A,B group were (0.31 ± 0.04),(0.30 ± 0.05),(0.35 ±0.14),(0.28 ±0.08),(0.16 ±0.07) g,compared with that of blank group (0.55 ±0.10) g with significantly reduced(P ＜ 0.01).The platelet aggregation rates of control-low,-high doses herb groups and combined A,B groups induced by PAF were (43.3 ± 4.7) ％,(37.2 ± 4.7) ％,(35.5 ± 4.1) ％,(35.0 ± 3.2) ％,when compared with that of blank group (52.9 ± 4.4) ％,they reduced significantly (P ＜ 0.01).The platelet aggregation rates of combined A,B group were significantly lower than that of control-low dose herb group (P ＜ 0.05).The PAF contents of control-low,-high doses herb groups and combined A,B groups were (1043 ± 162),(1010 ± 189),(973 ± 159),(959 ± 178) ng · L-1,significantly lower than that of blank group (1510 ± 319) ng · L-1 (P ＜ 0.01).The CD62P contents of control A,B groups,control-low,-high doses herb groups and combined A,B groups were (156 ± 13),(130 ±21),(101 ±17),(85 ±8),(107 ± 18),(107 ± 19) ng · mL-1,significantly lower than that of blank group (234 ±69) ng · mL-1(P ＜ 0.01).The PF-4 content of control A,B groups,control-high dose herb group and combined A,B groups were (148 ± 14),(255 ± 14),(322 ±69),(242 ±26),(266 ±36) ng· mL-1,which significantly reduced compared with that of blank group (478 ±91) ng · mL-1 (P ＜0.05,P ＜0.01).Conclusion Ligustrazine injection combined with aspirin and clopidogrel can play a synergistic anti-thrombosis effect.

Sixteen lignanoids were isolated from an aqueous extract of the commonly used Chinese traditional medicine Dangshen, the dried roots of Codonopsis pilosula, by using a combination of various chromatographic techniques, including silica gel, macroporous adsorbent resin, MCI resin, sephadex LH-20, and reversed phase semi-preparative HPLC. On the basis of spectral data analysis, their structures were elucidated and identified as (-)-(7R, 7'R, 8R, 8'S)-4, 4'-dihydroxy-3, 3', 5, 5', 7-pentamethoxy-2, 7'-cyclolignane (1), (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranosyl-(1"'→2")-β-D-glucopyranoside (2), (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol (3), (+)-(7S, 8R)-dehydrodiconiferyl alcohol (4), (+)-balanophonin (5), (+)-demethoxypinoresinol (6), (+)-pinoresinol (7), (+)-epipinoresinol (8), (-)-syringaresinol (9), (-)-medioresinol (10), (-)-lariciresinol (11), (-)-secoisolariciresinol (12), (-)-ent-isolariciresinol (13), (+)-(7S, 8S)-3-methoxy-3', 7-expoxy-8, 4'-neolignan-4, 9, 9'-triol (14), (+)-(7S, 8R)-3', 4-dihydroxy-3-methoxy-8, 4'-neolignan (15), and (-)-(7R, 8R)-3', 4-dihydroxy-3-methoxy-8, 4'-neolignan (16). All these compounds were isolated from C. pilosula for the first time, while compound 1 is a new natural product of 2, 7'-cyclolignan and 2 is a new 4', 7-epoxy-8, 3'-neolignan diglucoside. Compound 12 showed activity against Fe²⁺-cysteine induced rat liver microsomal lipid peroxidation with an inhibition ratio of (63.4±8.3)% at 1×10^-5 mol·L^-1.

Objective To analyze the cadmium level of main food,and to preliminarily assess the risk of dietary cadmium exposure among residents in Yantai.Methods A total of 925 samples of 10 kinds of food groups were collected from 14 counties (or districts)of Yantai.Cadmium contents in food were determined according to GB/T 5009.15—2003,and then the provisional tolerable monthly intake (PTMI)and the margins of safety(MOS)of cadmium were calculated by combining the concentration of cadmium in foods with food consumption data.Results The concentration of cadmium in 10 kinds of food groups was 26.47 μg/kg.The concentration of cadmium in sea foods was 92.48 μg/kg,and that was the highest among the 10 kinds of food groups.The concentration of cadmium in pluck,flour and vegetables were 47.35,33.25, 18.87 μg/kg respectively.Monthly dietary cadmium exposure quantity of flour,sea food,vegetable and rice was 295.70 μg,38.11 μg,32.09 μg and 10.87 μg,respectively.Flour as a most important contributor,contributed 76.09% of the total dietary cadmium exposure.Conclusion The average dietary cadmium exposure from the main food did not exceed the PTMI and the MOS was more than 1,so the level of dietary cadmium exposure is safe.However,based on the largest consumption of flour in Yantai and the high contribution rate of flour of dietary cadmium exposure,more attention should be paid to the possible cadmium contaminated wheat.