Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)％,(95.0±4.9)％and(90.7±6.3)％respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.
Carbohydrates ; Glycosides ; Oligosaccharides ; Oxidation-Reduction ; Polysaccharides/chemistry*

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.
Bacterial Infections ; Humans ; Polysaccharides/chemistry* ; Structure-Activity Relationship

The ribose and phosphorus contents in Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) are two important chemical indexes for the development and quality control of Hib conjugate vaccine. A quantitative ¹H- and ³¹P-NMR method using a single internal standard was developed for simultaneous determination of ribose and phosphorus contents in Hib CPS. Hexamethylphosphoramide (HMPA) was successfully utilized as an internal standard in quantitative ¹H-NMR method for ribose content determination. The ribose and phosphorus contents were found to be affected by the concentration of polysaccharide solution. Thus, 15-20 mg·L^-1 was the optimal concentration range of Hib CPS in D₂O solution for determination of ribose and phosphorus contents by this method. The ribose and phosphorus contents obtained by the quantitative NMR were consistent with those obtained by traditional chemical methods. In conclusion, this quantitative ¹H- and ³¹P-NMR method using a single internal standard shows good specificity, accuracy and precision, providing a valuable approach for the quality control of Hib glycoconjugate vaccines.
Haemophilus Vaccines ; Haemophilus influenzae type b ; Phosphorus ; Polysaccharides, Bacterial ; Ribose

D-Glycero-D-mannno-heptose 1β, 7-bisphosphate (HBPβ) is an important intermediate for constructing the core structure of Gram-negative bacterial lipopolysaccharides and was reported as a pathogen-associated molecular pattern (PAMP) that regulates immune responses. HBPβ with 3-O-amyl amine linker and its monophosphate derivative D-glycero-D-mannno-heptose 7-phosphate (HP) with 1α-amyl amine linker have been synthesized as candidates for immunity study of HBPβ. The O3-amyl amine linker of heptose was installed by dibutyltin oxide-mediated regioselective alkylation under fine-tuned protecting condition. The stereoselective installation of 1β-phosphate ester was achieved by NIS-mediated phosphorylation at low temperature. The strategy for installation of 3-O-amyl amine linker onto HBP derivative can be expanded to the syntheses of other conjugation-ready carbohydrates bearing anomeric phosphoester.

Seasonal outbreaks of airsacculitis in China's poultry cause great economic losses annually. This study tried to unveil the potential role of Avian metapneumovirus (AMPV), Ornithobacterium rhinotracheale (ORT) and Chlamydia psittaci (CPS) in avian airsacculitis. A serological investigation of 673 breeder chickens and a case-controlled study of 430 birds were undertaken. Results showed that infection with AMPV, ORT, and CPS was highly associated with the disease. The correlation between AMPV and CPS were positively robust in both layers and broilers. Finally, we determined the co-infection with AMPV, ORT, and CPS was prevalent in the sampled poultry farms suffering from respiratory diseases and the outbreak of airsacculitis was closely related to simultaneous exposure to all three agents.
Air Sacs ; microbiology ; pathology ; Animals ; Antibodies, Bacterial ; blood ; Antibodies, Viral ; blood ; Case-Control Studies ; Chickens ; Chlamydia ; Chlamydia Infections ; microbiology ; pathology ; veterinary ; Coinfection ; Flavobacteriaceae Infections ; microbiology ; pathology ; veterinary ; Humans ; Metapneumovirus ; Ornithobacterium ; Paramyxoviridae Infections ; pathology ; veterinary ; virology ; Poultry Diseases ; microbiology ; pathology ; virology ; Respiratory Tract Diseases ; microbiology ; veterinary ; virology ; Seroepidemiologic Studies

BACKGROUND: Bone morphogenetic protein 2 (BMP-2) has a strong ability to induce and promote the osteogenic differentiation of mesenchymal stem cells. OBJECTIVE: To evaluate the BMP-2 effect on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on an injectable nano-hydroxyapatite/chitosan (nHA/CS) composite scaffold. METHODS: (1) Experiment 1: Passage 3 BMSCs were divided into two groups and cultured with the nHA/CS scaffold or cultured alone. Cell counting kit-8 was used to detect cell proliferation at 1, 3, 5, 7, 14 days of culture. (2) Experiment 2: Passage 3 BMSCs were seeded onto the nHA/CS scaffold and cultured in culture medium containing BMP-2 or not. Alkaline phosphatase activity in cells was detected at 3, 6, 9, 12, 15 days of culture. Cell counting kit-8 was used to detect cell proliferation at 1, 3, 5, 7, 14 days of culture. Alizarin red staining was used to observe the osteogenic differentiation of cells at 1 and 2 weeks of culture. RESULTS AND CONCLUSION: (1) Experiment 1: With the prolongation of culture time, the absorbance values in the two groups were gradually increased, but there was no significant difference between the two groups. At 7 days of culture, the BMSCs adhered tightly to the scaffold surface. (2) Experiment 2: With the prolongation of culture time, the alkaline phosphatase activities in the two groups were gradually increased, and moreover, the alkaline phosphatase activity in the experimental group was higher than that in the control group at different culture time (P < 0.05). The absorbance values in the two groups were also gradually increased, and the value in the experimental group was higher than that in the control group at different culture time (P < 0.05). At 1 and 2 weeks of culture, the number of calcified nodules was higher in the experimental group than the control group. To conclude, BMP-2 has a promotion role in the proliferation and differentiation of BMSCs cultured on the injectable nHA/CS scaffold.

BACKGROUNDNontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population.

METHODSA nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH.

RESULTSNONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH.

CONCLUSIONSOur findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

Adult ; Age Distribution ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Female ; Femur Head Necrosis ; epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult

Objective To evaluate the safety of mefformin in the treatment of elderly type 2 diabetes mellitus(T2DM). Methods Two hundred and forty-three cases of elderly T2DM hospitalized from Jan.1996 to Dec. 2006 were reviewed; the changes of fasting blood glucose(FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), liver and renal function and blood lactic acid were evaluate before and after treatment. Results The mean time of treatment with mefformin was (6.6±3.9) years (3 months-21 years)in these 243 cases. The levels of FBG, PBG and HbAlc significantly reduced after treatment with mefformin only in 43 cases (17.7%), mefformin combined with other oral hypoglycemic drugs in 124 cases (51.0%) and mefformin combined with insulin in 76 cases (31.3%). There was only 18.1% of the cases with normal range ( > 80 ml/min) of creatinine clearance rate (Ccr), and 25.8% of the cases with Ccr≤50 ml/min. The liver and renal function as well as the blood lactic acid had no significant change after treatment no matter in total cases or in different groups separated by Ccr.Conclusions Mefformin is safety in the treatment of elderly T2DM patients. Ageing is not the contraindication of mefformin. To the patients with high risk, we should monitoring the level of blood lactic acid.