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

A flavoring agent and a suspension agent were prepared for extemporaneous compounding. The stability of the two agents before and after drug loading was investigated, and the taste of the suspension after extemporaneous compounding was evaluated by electronic tongue technology. The two agents remained stable under the conditions of influence factor test, accelerated test and long-term test. The appearance properties of the two agents did not change. The relative density of the flavoring agent was maintained at 1.053-1.075, and the pH was stable at 4.2-4.5. The relative density of the suspension agent was maintained at 0.999-1.022, and the pH was stable at 4.0-4.5. Seven kinds of drugs, including warfarin sodium tablets and spironolactone tablets, were mixed with these two oral solvents, and the content uniformity and stability were detected respectively. The results showed that the preparations could be evenly dispersed and the physical and chemical properties were stable. The results of taste evaluation showed that in captopril group and chloral hydrate group, the flavoring agent had the best effect on taste correction. In warfarin sodium group, rifampicin group, spironolactone group, vitamin B1 group and vitamin B2 group, the blending agents had the best effect on taste correction.

Currently, the gut-organ axis has become a hot research topic. As increasing attention has been paid to the role of gut microbiota in the health of organs, the complex and integrated dialogue mechanism between the gastrointestinal tract and the associated microbiota has been demonstrated in more and more studies. Skin as the largest organ in the human body serves as the primary barrier protecting the human body from damage. The proposal of the gut-skin axis has established a bidirectional link between the gut and the skin. The disturbance of gut microbiota can lead to the occurrence of skin diseases, the mechanism of which is complex and may involve multiple pathways in immunity, metabolism, and internal secretion. According to the theory of traditional Chinese medicine(TCM), the connection between the intestine and the skin can be established through the lung, and the interior disorders will definitely cause symptoms on the exterior. This paper reviews the research progress in the gut-skin axis and its correlation with TCM theory and provides ideas and a basis for cli-nical treatment and drug development of skin and intestinal diseases.
Humans ; Medicine, Chinese Traditional ; Gastrointestinal Tract ; Skin Diseases/drug therapy* ; Gastrointestinal Microbiome

Objective: To investigate the association between peripheral blood mitochondrial DNA copy number (mtDNAcn) and incident risk of liver cancer. Methods: At the baseline of Dongfeng-Tongji (DFTJ) cohort, 27 009 retirees were recruited from Dongfeng Motor Corporation in 2008. After excluding people without baseline DNA, with current malignant tumor and loss of follow-up, 1 173 participants were randomly selected into a sub-cohort by age-and gender-stratified sampling method at a proportion of 5% among all retirees. A total of 154 incident liver cancer cases identified from the cohort before December 31, 2018 (4 cases had been selected into the sub-cohort) were selected to form the case cohort of liver cancer. For the above 1 323 participants, their baseline levels of mtDNAcn in peripheral blood cells were measured by using quantitative real-time PCR method. The restricted cubic spline analysis was used to fit the shape of the association between baseline mtDNAcn and incident risk of liver cancer. The weighted Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95%CI. Results: In this case-cohort study, the median follow-up time was 10.3 years. The restricted cubic spline analysis indicated that the relationship between peripheral blood mtDNAcn and incident risk of liver cancer followed a U-shaped pattern (P_non-linear<0.05). All case-cohort population were divided into four subgroups by sex-specific quartiles of mtDNAcn levels among sub-cohort participants, when compared to participants in the Q₂ subgroup of mtDNAcn, those in the Q₁ subgroup (HR=2.00,95%CI:1.08-3.70) and Q₄ subgroup (HR=4.11,95%CI:2.32-7.26) both had a significantly elevated risk of liver cancer, while those in the Q₃ subgroup (HR=1.05,95%CI:0.54-2.05) had not. There were no significant multiply interaction effects of aging, gender, tobacco smoking, alcohol drinking and history of chronic hepatitis on the above association (P_interaction>0.05). Conclusion: Both extremely low and high baseline level of mtDNAcn in peripheral blood cells are associated with an increased risk of incident liver cancer, but the underlying mechanisms need to be further clarified.
Cohort Studies ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics* ; Female ; Humans ; Liver Neoplasms/genetics* ; Male ; Mitochondria

Objective: To investigate the predictive value of SYNTAX-Ⅱ score on long term prognosis of patients diagnosed with chronic total occlusion (CTO) and received percutaneous coronary intervention (PCI). Methods: Patients undergoing CTO-PCI in Fuwai hospital from January 2010 to December 2013 were enrolled in this retrospective analysis. The SYNTAX-Ⅱ score of the patients was calculated. According to SYNTAX-Ⅱ score tertiles, patients were stratified as follows: SYNTAX-Ⅱ≤20, 2027. Primary endpoint was major adverse cardiac events (MACCE), including all-cause death, myocardial infarction, stroke and any revascularization. Secondary endpoints included stent thrombosis, heart failure and target lesion failure (TLF). Patients were followed up by outpatient visit or telephone call at 1 month, 6 months and 1 year after PCI, and annually up to 5 years. Multivariate Cox regression model was used to analyze the independent risk factors of all-cause death in patients undergoing CTO-PCI. The predictive value of SYNTAX score with SYNTAX-Ⅱ score for all-cause death was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: A total of 2 391 patients with CTO and received PCI were enrolled in this study. The mean age was (57.0±10.5) years, 1 994 (83.40%) patients were male. There were 802 patients in lower tertile group (SYNTAX-Ⅱ≤20), 798 patients in intermediate group (2027). At the end of 5-year follow-up, the loss to follow-up rate of the three groups was 9.10%(73/802), 10.78%(86/798)and 8.85%(70/791), respectively. The rate of all-cause mortality (1.78% (13/729) vs. 3.65% (26/712) vs. 9.02% (65/721), P<0.001), cardiac death (1.37% (10/729) vs. 2.11% (15/712) vs. 4.85% (35/721), P<0.001), target vessel myocardial infarctions (4.25% (31/729) vs. 4.49% (32/712) vs. 7.07% (51/721), P=0.03), probable stent thrombosis (1.51% (11/729) vs. 2.81% (20/712) vs. 3.61% (26/721), P=0.04) and heart failure (1.78% (13/729) vs. 1.97% (14/712) vs. 5.41% (39/721), P<0.001) increased in proportion to increasing SYNTAX-Ⅱ score (all P<0.05). Multivariable Cox regression analysis indicated that female (HR=2.05, 95%CI 1.12-3.73, P=0.01), left ventricular ejection fraction (HR=0.97, 95%CI 0.95-1.00, P=0.05) and SYNTAX-Ⅱ score (HR=1.07, 95%CI 1.02-1.11,P=0.01) were independent predictors for all-cause mortality in patients undergoing CTO-PCI. The predicted value of the SYNTAX-Ⅱ score for all-cause death was significantly higher than the SYNTAX score (AUC 0.71 vs. 0.60, P=0.003). Conclusion: For CTO patients who underwent percutaneous coronary intervention, SYNTAX-Ⅱ score is an independent predictor for 5-year all-cause death, and SYNTAX-Ⅱ serves as an important predictor for all-cause death in these patients.
Humans ; Male ; Female ; Middle Aged ; Aged ; Percutaneous Coronary Intervention ; Coronary Artery Disease ; Retrospective Studies ; Stroke Volume ; Treatment Outcome ; Ventricular Function, Left ; Myocardial Infarction ; Prognosis ; Risk Factors ; Heart Failure ; Coronary Occlusion/surgery*

Objective To investigate the effect of facet joint asymmetry on lumbar biomechanics in normal and patients with adolescent lumbar disc hemiation (ALDH). Methods Mimics 21.0, 3-Matic Medical 13.0, Geomagic Wrap 2017, HyperMesh 2019 and finite element software ABAQUS 2021 were combined to establish three-dimensional finite element models of nonnal lower lumbar spine and adolescent lumbar disc hemiation. According to the difference between the left and right facet joints, three cases of nonnal and ALDH patients aged 13-18 years old were selected, with a total of 6 cases. The stress of intervertebral disc under different torque loads (neutral position, lateral flexion and rotation) was analyzed and compared. Results 1. Three dimensional finite element models of L3-L, segments were established in 6 male nonnal and adolescent patients with lumbar disc herniation, and the stress and displacement nephogram of lumbar disc hemiation in nonnal neutral position, flexion, extension, lateral flexion and rotation were obtained; 2. The stress of L4_, annulus fibrosus increased when the facet joint angle of nonnal adolescents was symmetrical in the neutral position; 3. The stress of annulus fibrosus was greater than that of nucleus pulposus under different conditions, and the stress of annulus fibrosus was flexion > neutral position > extension; 4. In patients with ALDH, the left side of the facet joint was larger than the right 10 ° model, and the stress in the posterior side of the annulus fibrosus of L4_, segment increased significantly under extension condition. Under lateral flexion condition, the left stress of the left annulus fibrosus was compared with the right stress of the right annulus fibrosus, t = l. 575, P<0. 05, the difference was statistically significant, the right stress of the right annulus fibrosus was greater than the left stress of the left annulus fibrosus. Under the rotating condition, the stress on the left and right sides of the fiber ring was greater than that on the back side. Conclusion 1. Compared with nonnal and patients with ALDH, the stress of intervertebral disc increases under different postures, which ma)' increase the shear load of intervertebral disc and aggravate the process of intervertebral disc degeneration; 2. When the degree of left-right asymmetry of facet joint is more than 10 degrees, the stress on the side with small degree is greater. Facet joint asymmetry can lead to the overload of vertebral bod)' and intervertebral disc, leading to spinal instability; 3. The stress of intervertebral disc in extension is less than that in neutral position and flexion. Extension can relieve the pressure of intervertebral disc and play an auxiliary role in the recovery of patients with ALDH.

Objective: To investigate the impact of different levels of systolic blood pressure on all-cause, cardiovascular and cerebrovascular mortality in patients with nonvalvular atrial fibrillation (AF). Methods: This is a prospective cohort study. Patients with AF or atrial flutter diagnosed by 12 lead electrocardiogram during physical examination of Kailuan Group employees from July 2006 to December 2017 or previously diagnosed with AF in an inpatient setting at a level 2A hospital or above were eligible for the study. Baseline clinical characteristics including age, gender, systolic blood pressure were collected. According to the level of systolic blood pressure, patients were divided into systolic blood pressure<120 mmHg (1 mmHg=0.133 kPa)group, 120 mmHg ≤ systolic blood pressure<140 mmHg group, and systolic blood pressure ≥140 mmHg group. The time of first diagnosis with AF was defined as the start of follow-up and the final follow-up ended at December 2018. Primary endpoint was all-cause death. Related information was obtained through the social security system or inpatient medical records. The cause of death was defined according to the International Classification of Diseases disease (ICD-10) codes by professional medical stuffs. Multifactorial Cox proportional risk model was used to analyze the relative risk ratios for the occurrence of death in different systolic blood pressure level groups. The relationship between systolic blood pressure levels and mortality in the patients with AF was analyzed by using natural spline function curves. Results: A total of 1 721 patients with AF were enrolled (average age=(67.0±9.0) years), patients were followed up for (6.3±3.8) years. 544 out of 1 721 patients with AF died during the follow-up period (31.61%). The cumulative incidence rate of all-cause mortality, cardiovascular and cerebrovascular death was 26.13%, 25.59%, 36.96% and 14.86%, 11.87%, 19.76% respectively in the systolic blood pressure<120 mmHg, 120 mmHg ≤ systolic blood pressure<140 mmHg and systolic blood pressure ≥140 mmHg groups. The cumulative incidence rate of all-cause, cardiovascular and cerebrovascular death was significantly higher in the group with systolic blood pressure ≥140 mmHg than in 120 mmHg ≤ systolic blood pressure<140 mmHg group (P<0.05). Compared with 120 mmHg ≤ systolic blood pressure<140 mmHg group, multivariable Cox proportional hazards regression models showed that the HRs (95%CI) for all-cause, cardiovascular and cerebrovascular death were 1.47 (1.20 to 1.79) and 1.69 (1.27 to 2.26) for the group with systolic blood pressure ≥ 140 mmHg (P<0.05). In contrast, the HRs (95%CI) for all-cause, cardiovascular and cerebrovascular death in the systolic blood pressure<120 mmHg group were 0.99 (0.73-1.35) and 1.24 (0.82-1.89), respectively, with no statistically significant differences between the two groups (P>0.05). The natural spline curve showed that there was a "U" relationship between systolic blood pressure levels and all cause death and cardiovascular and cerebrovascular death in this patient cohort. Systolic blood pressure greater than or less than 123 mmHg was associated with increased risk of death of AF patients in this cohort. Conclusion: Compared with systolic blood pressure<120 mmHg and systolic blood pressure≥140 mmHg group, the risk of all-cause and cardiovascular and cerebrovascular death is the lowest in AF patients with 120 mmHg ≤ systolic blood pressure<140 mmHg in this cohort.

Objective: To evaluate the safety and long-term clinical efficacy of percutaneous coronary intervention (PCI) in patients with in-stent chronic total occlusion (IS-CTO) lesions. Metheds: This is a retrospective analysis. Patients with IS-CTO who underwent PCI in Fuwai hospital from January 2010 to December 2013 were enrolled. A total of 212 patients who met the inclusion criteria were included in the IS-CTO group, 212 matched patients with primary CTO lesions were included in the de novo CTO group. The incidence of complications and the success rate of PCI were compared between the two groups. Successful PCI was defined as successfully implantation of stent(s) at target CTO lesions. The primary endpoint was defined as a composite event of cardiac death and myocardial infarction (MI). Secondary endpoints including PCI success, all-cause death, cardiac death, MI, target vessel related MI, revascularization, target vessel revascularization, heart failure for rehospitalization. The patients were followed up for 5 years after PCI. Results: A total of 424 cases were included. The mean age was (57.8±10.5) years, there were 364 males in this cohort. The left ventricular ejection fraction was significantly lower ((58.7±9.2)% vs. (61.0±7.7)%, P=0.01) and the SYNTAX scores was significantly higher (19.4±8.3 vs. 15.3±10.0, P<0.01) in IS-CTO group than that in de novo CTO group. The proportion of patients with target CTO lesions in left anterior descending artery was significantly higher (42.9% (50/212) vs. 23.6% (91/212), P<0.01) in IS-CTO group than that in de novo CTO group. The rate of successful PCI (71.7% (152/212) vs. 69.8% (148/212), P=0.70) and complication (40.6% (86/212) vs. 36.3% (77/212), P=0.37) was similar between the two groups. The incidence of primary endpoint at 5 years was significantly higher in IS-CTO group (10.8% (23/212) vs. 4.7% (10/212), P=0.02), which was driven by higher incidence of MI (9.0% (19/212) vs. 4.2% (9/212), P=0.05). There were a trend of higher secondary endpoints in IS-CTO group (all P>0.05). Conclusion: The safety and effectiveness of PCI are acceptable in patients with IS-CTO, but the risk of long-term cardiac death and MI is higher among patients with IS-CTO as compared to patients with primary CTO lesions.

Objective To measure the anatomical structure of the occipital condyle (OC) and the occipital foramen (FM) by three-dimensional reconstruction, and to analyze the morphological characteristics and relative positional relationship of the occipital condyle and occipital foramen, in order to provide anatomical parameters for the imaging diagnosis of the craniocervical junction and the choice of surgical approach. Methods Sixty normal subjects were selected with CT scans of the skull and upper cervical spine, including 30 males and 30 females, aged 20-65 (48. 18±16. 17) years old. The data were imported into the Syngo.via VB10B software, and the skull was reconstructed in three dimensions. To observe the shape of the occipital condyle and occipital foramen, and to measure the occipital condyle length, width, height, condyle inclination angle(CIA), longitudinal diameter, transverse diameter, area of the occipital foramen, the maximum distance between the cranial eyebrow and the posterior cranial point (SML), the crimson eyebrow on the SML line, the distance from the interpoint to the posterior margin of the occipital condyle (GOCP), the vertical distance between the anterior edge of the occipital foramen to the posterior margin of the occipital condyle (AOCP), and the distance from the medial margin of the left and right occipital condyles to the Y axis (OC-M), left and right occipital condyle posterior margin to X axis distance (OC-P); occipital condyle classification index (OCI), occipital condyle relative index of head (SOCI), midpoint on the SML straight line to the occipital condyle Marginal connection distance (COCP,COCP =GOCP-SML/ 2), and determine the type of relative positional relationship between left and right occipital condyles. Results The differences in anatomical length, width and height of the occipital condyle were statistically significant (P<0. 05), and men were larger than women; the occipital foramen area, longitudinal diameter of the occipital foramen, SML, GOCP, AOCP had statistical differences (P<0. 05). The lateral differences of occipital condyle inclination were statistically significant (P<0. 05), and the left side was greater than the right side. The differences in OC-M and OC-P sides were statistically significant (P<0. 05). The former was larger on the right than on the left; the latter was larger on the left than on the right. The longitudinal diameter of the occipital foramen was positively correlated with the area of the occipital foramen and AOCP; OCI classification result were as follows: typeⅠ(OCI<0. 45) had 8 cases (13. 33%), type Ⅱ (0. 45≤OCI<0. 50) had 47 cases (78. 33%), type Ⅲ (OCI≥0. 50) had 5 cases (8. 33%). SOCI classification result were as follows: type Ⅰ (SOCI< 0. 60) had 2 cases (3. 33%), type Ⅱ (0. 60≤SOCI<0. 75) had 54 cases (90. 00%), type Ⅲ (SOCI≥0. 75) had 4 cases (6. 67%). Conclusion The anatomical parameters of the occipital condyle in Inner Mongolia can be implanted with occipital condylar screws. The position of the occipital condyle relative to the foramen magnum and the skull is highly variable.

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.