Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.
Adult ; Humans ; Child ; Adolescent ; Inotuzumab Ozogamicin ; Receptors, Chimeric Antigen ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Antibodies, Monoclonal ; Adaptor Proteins, Signal Transducing ; Antigens, CD19 ; Chemical and Drug Induced Liver Injury

The processing of Chinese medicine is a unique and dialectical treatment of traditional Chinese medicine in clinic.The processing theory of "leading vinegar-processing Chinese medicine into liver" is one of the traditional processing theories of Chinese medicine.The vinegar-processing Chinese medicine under the guidance of the processing theory typically reflects the characteristics of "reducing toxicity and enhancing efficacy" of the processing of Chinese medicine.This paper traced the origin and discussed the connotation of the traditional theory of "leading vinegar-processing Chinese medicine into liver".Combined with the research status of "lea-ding vinegar-processing Chinese medicine into liver", this paper explored the mechanism of "leading vinegar-processing Chinese medicine into liver" from the aspects of material basis, medicine effect, and traditional Chinese medicine(TCM) meridian, and analyzed the existing problems in the current research.This paper reviewed the modern study on reducing toxicity and enhancing efficacy of vinegar-processing Chinese medicine, and deeply explored the scientific connotation of the traditional processing theory of "leading vinegar-processing Chinese medicine into liver".At the same time, the research trend and idea of the effect mechanism of "leading vinegar-processing Chinese medicine into liver" based on the Quality markers(Q-Marker) of TCM, biological targets, and clinical prescriptions were put forward, providing references for the further study on "leading vinegar-processing Chinese medicine into liver".This paper also provided a scientific basis for the rational selection of processed products in TCM clinical practice.
Acetic Acid ; Biomarkers ; Drugs, Chinese Herbal ; Liver ; Medicine, Chinese Traditional ; Meridians

In order to reveal the regional characteristics of nucleosides and amino acids in Elaphuri Davidiani Cornu,39 samples of Elaphuri Davidiani Cornu collected from 4 different regions were analyzed by UPLC-QTRAP ~®/MS2 method followed by orthogonal partial least-squares discrimination analysis( OPLS-DA) and cluster analysis( CA). The results showed all the samples contained abundant nucleosides and amino acids,with the total content of 45. 09 μg·g~(-1) and 634. 80 μg·g-1,respectively. The samples presented significant regional differences in the contents of individual components,and the main differential components included Ura,Hpro,Thr,Glu,G5 P,2'-dG,Adeno,Met,Ade,Gln,Orni,Phe,2'-dA,Hit,Lys,and Ile. Among them,Ura,Met,Glu,and Ile had the highest content in the samples from Dafeng in Jiangsu,Qinhu in Jiangsu,Beijing,and Shishou in Hubei,respectively. OPLS-DA and CA demonstrated that all the samples of Elaphuri Davidiani Cornu could be divided into three categories,reflecting the regional characteristics. The results indicated that the accumulation of nucleosides and amino acids in Elaphuri Davidiani Cornu was closely related to its habitat,providing a useful reference for the research on the quality formation,quality evaluation and control,as well as the comprehensive utilization of Elaphuri Davidiani Cornu. The findings suggested that the content factors of Ura,Met,Glu,and Ile could be included into the quality standard system of Elaphuri Davidiani Cornu as the characteristics of medicinal materials from different regions.
Amino Acids ; Beijing ; Cornus ; Nucleosides

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, CONCLUSIONS Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia ; Asphyxia Neonatorum/epidemiology* ; Humans ; Hyperglycemia ; Infant, Newborn ; Prognosis ; Retrospective Studies

Transient osteoporosis of the hip(TOH) is classified as a type of bone marrow edema syndrome. TOH is lack of previous study and there is still controversy about his pathogenesis. In recent years, with the development of multi-discipline, such as imaging, pathology, molecular biology, the study has found that the pathological mechanism is complex, while its mechanism is still not clear, which need further research. This paper summarizes the research progress on the pathogenesis of TOH from neurogenic, osteonecrosis, abnormal vascular function, subchondral fracture, heredity and regional acceleration and son on.

OBJECTIVE: To investigate the clinical effectiveness of polytheretherketone (PEEK) cages assisted anterior cervical discetomy and fusion (ACDF) to treat cervical spondylosis with sympathetic symptoms. METHODS: Retrospective analysis was undertaken for 39 patients who were diagnosed as cervical spondylosis with sympathetic symptoms and underwent ACDF with PEEK cages. Radiographs obtained before surgery, after surgery, and at the final follow-up were assessed for quality of fusion. The following criteria were used for assessing radiographic success of fusion: (1) endplate obliterated with no lucent lines; (2) obliteration of disc space by bony trabeculae; (3) less than 2°of intervertebral motion or 2 mm of motion between the spinous processes at the operated segment on flexion-extension lateral radiographs. The sympathetic symptoms including vertigo, headache, tinnitus, nausea and vomiting, heart throb, hypomnesia and gastroenterological discomfort were scored by 20-point system preoperatively, 2 months postoperatively and at the final follow-up. The recovery rate and clinical satisfaction rate were also evaluated. Surgical complications were also assessed. RESULTS: They were followed up for at least one year. The mean follow-up was 15.6 months. Radiographs of the cervical spine at the last follow-up revealed a solid fusion with no signs of a pseudoarthrosis in 36 cases. In two patients delayed union and bony fusion were achieved at the end of 9 and 11 months. Pseudoarthosis was found in 1 case but the patient had no symptoms. The score of sympathetic symptoms before surgery, 2 months after surgery and at the final follow-up were 8.4±1.0,2.2±0.3,and 2.4±0.3, respectively. There were 22 excellent cases, 15 good cases, 1 fair case and 1 bad case in terms of RR. Good to excellent results were attained in 95% of theses patients. The sympathetic symptoms improved in all the patients and the score was significantly improved after surgery. There was one patient who had cerebral spinal fluid leakage but he recovered one week after surgery. Two patients felt a mild swallowing discomfort, but it disappeared within one month after surgery. Subcutaneous hematoma occurred in one patient due to obstructed drainage. It was cleared two days after surgery. CONCLUSION Cervical spondylosis patients with sympathetic symptoms may be managed successfully with ACDF using PEEK cages. Successful clinical results regarding symptom improvement and general satisfaction with the surgical procedure depend not only on obtaining successful decompression and radiographic fusion but also on patient selection.
Cervical Vertebrae/surgery* ; Decompression, Surgical ; Diskectomy ; Humans ; Male ; Nausea ; Neurosurgical Procedures ; Radiography ; Retrospective Studies ; Spinal Fusion ; Spondylosis/surgery* ; Treatment Outcome ; Vomiting

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to esti-mate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the asso-ciation between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients. Patients and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients. The pathologic response was evaluated according to the tumor regression grade (TRG). The prognostic role of pathologic response in recurrence-free survival (RFS) and overall survival (OS) was assessed using Kaplan–Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal–Wallis/Mann–WhitneyU tests. Results: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy (median RFS: 9.9 vs. 6.5 months,P= 0.009; median OS: 40.7 vs. 28.1 months,P= 0.040). Multivariate logistic regression and Kruskal–Wallis/Mann–WhitneyU tests showed that metastases with small diameter, metastases from the left-side primary tumors, and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases (allP < 0.05). A decrease in the serum carcinoembryonic antigen (CEA) level after preopera-tive chemotherapy predicted an increased pathologic response rate (P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemother-apy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens. Conclusions: We found that the evaluation of pathologic response may predict the prognosis of Chinese colo-rectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

BACKGROUNDThe initial classic classification of duplex kidney into complete (two ureters) and incomplete ("Y" shaped ureter) types are based on the ureter status. At the meantime, the features of the upper and lower moieties of duplex kidney were very crucial for appropriate procedure of hemi-nephrectomy, which was most commonly used for addressing the issues caused by a duplex kidney; and recently more applications of laparoscopy were used. In this study, we aimed prudently to propose a new classification based on the features of the upper and lower moieties of duplex kidney.

METHODSSixty-five children with 83 duplex kidneys were reviewed retrospectively. Based on kidney morphology found in CT urography and surgical findings, duplex kidney was classified into five types.

RESULTSThe first was the appendant type (36/83) and its feature was that the mini upper moiety was located on top of the lower one, with a visualized shallow groove between them. The ureter was dilated with an ectopic orifice or ureterocele. The second was the embedded type (13/83), the feature of which was that mini upper moiety located in the interior top of the lower one within the same capsule. The upper ureter was dilated with an ectopic orifice or ureterocele. The third was the hydronephrosis type (12/83). The severe hydronephrotic upper moiety was almost as big as the lower moiety. The upper ureter was severely dilated and circuitous with an ectopic orifice. The forth was the dual-poor type (2/83). The two moieties were all very small with "Y" shaped ureters and ectopic orifices. The last was the dual-well type (20/83). The upper moiety was almost the same size as the lower one, without apparent dilation of "Y" shaped or double ureters.

CONCLUSIONBased on kidney morphology, duplex kidney can be mainly classified into five types which can be depicted by CT urography prior to management and can provide an aid in selecting a successful course of surgical correction.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Kidney ; abnormalities ; diagnostic imaging ; Kidney Diseases ; diagnosis ; diagnostic imaging ; Male ; Radiography ; Retrospective Studies

BACKGROUNDStaphylococcus aureus (S. aureus) remains as an important microbial pathogen resulting in community and nosocomial acquired infections with significant morbidity and mortality. Few reports for S. aureus in lower respiratory tract infections (LRTIs) have been documented. The aim of this study was to explore the molecular epidemiology of S. aureus in LRTIs in China.

METHODSA multicenter study of the molecular epidemiology of S. aureus in LRTIs was conducted in 21 hospitals in Beijing, Shanghai and twelve other provinces from November 2007 to February 2009. All the collected S. aureus strains were classified as minimum inhibitory concentration (MIC), mecA gene, virulence genes Panton-Valentine Leukocidin (PVL) and γ-hemolysin (hlg), staphylococcal cassette chromosome mec (SCCmec) type, agr type, and Multilocus Sequence Typing (MLST).

RESULTSTotally, nine methicillin-sensitive S. aureus (MSSA) and 29 methicillin-resistant S. aureus (MRSA) strains were isolated after culture from a total of 2829 sputums or bronchoalveolar lavages. The majority of MRSA strains (22/29) had a MIC value of ≥ 512 µg/ml for cefoxitin. The mecA gene acting as the conservative gene was carried by all MRSA strains. PVL genes were detected in only one S. aureus strain (2.63%, 1/38). The hlg gene was detected in almost the all S. aureus (100% in MSSA and 96.56% in MRSA strains). About 75.86% of MRSA strains carried SCCmec III. Agr type 1 was predominant (78.95%) among the identified three agr types (agr types 1, 2, and 3). Totally, ten sequence type (ST) of S. aureus strains were detected. A new sequence type (ST1445) was found besides confirming ST239 as the major sequence type (60.53%). A dendrogram generated from our own MLST database showed all the bootstrap values ≤ 50%.

CONCLUSIONOur preliminary epidemiology data show SCCmec III, ST239 and agr type 1 of S. aureus as the predominant strains in LRTIs in Mainland of China.

Alleles ; Anti-Bacterial Agents ; therapeutic use ; China ; epidemiology ; Drug Resistance, Bacterial ; genetics ; Humans ; Microbial Sensitivity Tests ; Prospective Studies ; Respiratory Tract Infections ; epidemiology ; Staphylococcal Infections ; epidemiology ; Staphylococcus aureus ; drug effects ; pathogenicity

BACKGROUNDLiver cirrhosis is the fatal consequence of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a broad population with alcoholism or hepatitis B virus (HBV) infection remains difficult. In this study, we used a metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis.

METHODSSerum specimens were collected prospectively from normal control subjects (n = 22) and patients with alcoholic cirrhosis (n = 18) or HBV-induced cirrhosis (n = 19). The serum metabonome was analyzed using ultraperformance liquid chromatography (LC)/time-of-flight mass spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA).

RESULTSSignificant differences in the metabonomics among the three groups were observed. Lysophosphatidyl cholines (LPCs) (LPC C16:0, LPC C18:0, LPC C18:2, LPC C18:3, LPC C20:3, LPC C20:5) were decreased in the serum of patients with hepatic cirrhosis, whereas bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and stearamide were increased in the serum of patients with hepatic cirrhosis. These metabolites are considered "common" biomarkers for hepatic cirrhosis. Oleamide and myristamide were increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis.

CONCLUSIONSThere are significant metabonomic differences between alcohol- and HBV-induced liver cirrhosis. Metabonomics is a top-down systems biology tool for conducting research on clinical problems.

Adult ; Aged ; Alcohols ; adverse effects ; Chromatography, Liquid ; methods ; Female ; Hepatitis B virus ; pathogenicity ; Humans ; Liver Cirrhosis ; blood ; etiology ; metabolism ; virology ; Male ; Mass Spectrometry ; methods ; Middle Aged ; Principal Component Analysis