ObjectiveTo explore the potential molecular mechanism of Qizhu Kang'ai Formula （芪术抗癌方， QZKAF） for the treatment of colorectal cancer （CRC）. MethodsNetwork pharmacology was used to analyze the active ingredients and targets of QZKAF for CRC， and analyze the key targets of QZKAF for the treatment of CRC by gene function annotation （GO） and Kyoto Encyclopedia of Genomes （KEGG） pathway enrichment analysis. Molecular docking was applied to predict the binding activity of the core active ingredients to the key targets. A orthotopic transplantation tumor mice model of CRC was established to validate the key targets of QZKAF for CRC obtained from network pharmacology analysis. Forty-eight mice were randomly divided into the sham operation group， the model group， the 5-fluorouracil （5-Fu） group， and the QZKAF low-， medium-， and high-dose groups， with 8 mice in each group. Except for the sham operation group， the remaining groups underwent colon cancer orthotopic transplantation tumor modeling. The 5-Fu group was given 30 mg/kg of 5-Fu by intraperitoneal injection once every 3 days on the alternate day after modeling， while the QZKAF low-， medium-， and high-dose groups were given 2.925， 5.85， and 11.7 g/（kg·d） of QZKAF by gastric gavage， respectively， and the sham-operation group and the model group were gavaged with 0.1 ml/10 g of normal saline every day， all for 21 days. The in situ tumors mass and the number of liver metastases were compared between the groups. The pathological changes of colon tumor tissues were observed by HE staining， and the protein expression of protein tyrosine phosphatase nonreceptor type 1 （PTPN1）， vinculin， integrin subunit αν， integrin subunit β3， and E-cadherin were detected in colon tumor tissues by Western blot. ResultsNetwork pharmacology screening yielded that the top six core active ingredients of QZKAF intervening in CRC were quercetin， kaempferol， apigenin， luteolin， baicalein and ursolic acid. There were 212 targets of action， and the ranked top three were prostaglandin endoperoxide synthase 1 （PTGS1）， prostaglandin endoperoxide synthase 2 （PTGS2）， and PTPN1， which may be the key targets of QZKAF in the treatment of CRC. These key targets were significantly enriched mainly in phosphatidylinositol 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， focal adhesion and adhesion junction. Molecular docking results： except for PTGS1 with better binding activity to quercetin， kaempferol， and apigenin （binding energy ≥-7.0 kcal/mol）， PTGS1 showed strong binding activity to lignans， baicalein， ursolic acid， as well as PTGS2 and PTPN1 to the six core active ingredients （binding energy ＜-7.0 kcal/mol）. Experimental validation results： the protein expression of PTPN1， vinculin， integrin subunit αν， integrin subunit β3 in the colon tumor tissues of mice in the model group significantly increased， and the expression of E-cadherin significantly decreased compared to those in the sham operation group （P＜0.05）. Compared to those in the model group， the mass of the in situ tumors was reduced， and the number of hepatic metastasis nodules decreased in the high- and medium-dose QZKAF groups （P＜0.05）； the expression levels of PTNP1， vinculin， integrin subunit αν， integrin subunit β3 and E-cadherin in all QZKAF groups and 5-Fu group showed different degrees of retracement， and the changes of the indicators in all QZKAF groups showed a certain degree of dose-dependence （P＜0.05）. HE staining showed that the nuclei of tumor cells in the model group were mostly schizophrenic， and there were different degrees of nuclear fragmentation of tumor cells in all QZKAF groups with more in the medium- and high-dose groups. ConclusionQZKAF could inhibit the growth of in situ tumors and liver metastasis of CRC. Its mechanism might be related to the regulation of tumor cell-cell and tumor cell-extracellular matrix adhesion by PTPN1.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

Objectives: To evaluate microvascular perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction after revascularization using myocardial contrast echocardiography (MCE), and to explore clinical influencing factors of abnormal microvascular perfusion in these patients. Methods: This is a cross-sectional study. The analysis was performed among patients admitted to Peking University People's Hospital for acute ST-segment elevation myocardial infarction (STEMI) from June 2018 to July 2021. All patients underwent percutaneous coronary intervention (PCI) and completed MCE within 48 hours after PCI. Patients were divided into normal myocardial perfusion group and abnormal perfusion group according to the myocardial perfusion score. The echocardiographic indexes within 48 hours after PCI, including peak mitral valve flow velocity (E), mean value of early diastolic velocity of left ventricular septum and lateral mitral annulus (Em), left ventricular global longitudinal strain (GLS) and so on, were analyzed and compared between the two groups. Multivariate logistic regression analysis was used to evaluate the influencing factors of myocardial perfusion abnormalities. Results: A total of 123 STEMI patients, aged 59±13 years with 93 (75.6%) males, were enrolled. There were 50 cases in the normal myocardial perfusion group, and 73 cases in the abnormal myocardial perfusion group. The incidence of abnormal myocardial perfusion was 59.3% (73/123). The left ventricular volume index ((62.3±18.4)ml/m² vs. (55.1±15.2)ml/m², P=0.018), wall motion score index (WMSI) (1.59 (1.44, 2.00) vs. 1.24(1.00, 1.47), P<0.001) and mitral E/Em (17.8(12.0, 24.3) vs. 12.2(9.2, 15.7), P<0.001) were significantly higher whereas left ventricular global longitudinal strain (GLS) ((-10.8±3.4)% vs. (-13.8±3.5)%, P<0.001) was significantly lower in the abnormal myocardial perfusion group than those in the normal myocardial perfusion group. Multivariate logistic regression analysis showed that left anterior descending (LAD) as culprit vessel (OR=3.733, 95%CI 1.282-10.873, P=0.016), intraoperative no/low-reflow (OR=6.125, 95%CI 1.299-28.872, P=0.022), and peak troponin I (TnI) (OR=1.018, 95%CI 1.008-1.029, P=0.001) were independent risk factors of abnormal myocardial perfusion. As for ultrasonic indexes, deceleration time of mitral E wave (OR=0.979, 95%CI 0.965-0.993, P=0.003), mitral E/Em (OR=1.100, 95%CI 1.014-1.194, P=0.022) and WMSI (OR=7.470, 95%CI 2.630-21.222, P<0.001) were independently related to abnormal myocardial perfusion. Conclusions: The incidence of abnormal myocardial perfusion after PCI is high in patients with acute STEMI. Abnormal myocardial perfusion is related to worse left ventricular systolic and diastolic function. LAD as culprit vessel, intraoperative no/low-reflow and peak TnI are independent risk factors of abnormal myocardial perfusion.
Male ; Humans ; Female ; ST Elevation Myocardial Infarction/diagnostic imaging* ; Percutaneous Coronary Intervention ; Cross-Sectional Studies ; Coronary Circulation ; Echocardiography ; Anterior Wall Myocardial Infarction/etiology* ; Ventricular Function, Left ; Perfusion

Objective:To reconstruct the dose of nasopharyngeal carcinoma and verify the results of the whole-process radiotherapy plan based on log files and cone beam CT (CBCT).Methods:A total of 15 patients with nasopharyngeal carcinoma who received volumetric modulated arc therapy (VMAT) with Halcyon accelerator in the Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February to September 2022 were retrospectively selected. Log files and CBCT for all fractionated radiotherapy were recorded. The errors of monitor unit (MU), gantry angle, and multi-leaf collimator (MLC) leaf position per control point were analyzed. The adaptive CT (aCT) were generated according to CBCT and planned CT (pCT) using a commercial software Velocity TM, and the similarities among aCT, pCT and CBCT were analyzed. The original plan was modified from the log files and imported into the treatment planning system to calculate the delivered dose on the corresponding fractionated aCT to reconstruct the fractionated dose. And all the reconstructed doses were mapped back to pCT to obtain the cumulative dose. Theγpass ratios with criteria of 2 mm/2% and 2 mm/3% and the dose differences between the planned dose and the cumulative dose in the planning target volume (PTV) and organs at risk (OAR) were compared. Results:The root mean square (RMS) and the 95th percentile of the errors of MU, gantry angle and MLC leaf position errors were within an acceptable range. The aCT generated by Velocity TM had the anatomical structure of CBCT and the resolution, contrast, noise characteristics of pCT, which could be directly used for dose calculation. Compared with the planned dose, the changes of V 70 Gy of nasopharyngeal primary tumor (PTV nx), V 68 Gy of cervical glands (PTV nd) and V 60 Gy of planning target volume (PTV1) were -0.88%±1.91%, -2.99%±2.99% and -0.63%±0.93%, respectively, and V 40 Gy of parotid gland was increased to 2.65%±2.63%. Cumulative dose showed different degrees of PTV dose decrease ( P<0.05) and parotid dose was increased ( P<0.05). The γ pass ratio (2 mm/3%) between the cumulative dose and planned dose was 97.3%±2.7% and >95.0% in 86.7% of patients. Conclusions:Based on the log files and CBCT, the whole-process dose reconstruction of nasopharyngeal carcinoma patients can be carried out. According to the results of dose reconstruction, the radiotherapy effect of the target area and OAR can be quantitatively evaluated. In the case of high dose coverage and conformity of the original plan, the reconstruction results show that the cumulative dose coverage of the target area is decreased, whereas that of the parotid gland is increased.

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To investigate the difference in the efficacy of extended trochanteric osteotomy (ETO) and subtrochanteric shortening osteotomy (SSO) in total hip arthroplasty (THA) for Crowe type IV developmental dysplasia of the hip (DDH).Methods:Forty patients (51 hips) who underwent primary THA for Crowe type IV DDH from April 2012 to August 2020 at the First Affiliated Hospital of Soochow University and the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The patients were classified into ETO (extended greater trochanteric osteotomy) group and SSO(subtrochanteric shortening osteotomy) group. There were 12 patients (14 hips) in the ETO group, with 3 males and 9 females, aged 49.9±16.7 years old (range, 22-75 years old) and 28 patients (37 hips) in the SSO group, with 7 males and 21 females, aged 50.3±14.0 years (range, 22-76 years). In both groups, Harris hip score (HHS), leg length discrepancy, limp, Trendelenburg sign were used to evaluate the functional results and anteroposterior radiographs of the pelvis were taken at each follow-up to assess bone healing at the osteotomy site, periprosthetic osteolysis, bone ingrowth and periprosthetic loosening. Complications were recorded and analyzed.Results:All 51 hips were followed up for at least 24 months. The operative time and total blood loss was 116.8±14.2 vs. 128.3±19.2 min and 650.8±191.4 vs. 808.3±151.3 ml in the ETO group and the SSO group with significant difference ( t=2.04, P=0.047; t=3.08, P=0.003) respectively. At the follow-up of 24 months the HHS of ETO and SSO groups were 94.8±6.3 vs. 93.9±4.9 points and the leg length discrepancy was 4.6±2.2 vs. 5.2±3.0 mm. The positive rate of Trendelenburg's sign was 7% vs. 16% and the incidence of limp was 17% vs. 29% in the ETO group and the SSO group with no significant difference ( t=0.54, P=0.591; t=0.68, P=0.499; P=0.657; P=0.693). The length of femoral shortening in the ETO group and SSO group was 30.8±4.1 vs 35.3±7.9 mm with significant difference ( t=2.02, P=0.049). Time for bone healing at the osteotomy site was 5.8±1.5 vs. 6.0±1.4 months and the incidence of intraoperative femoral fractures was 36% and vs. 65% with no significant difference ( t=0.45, P=0.657; χ 2=3.52, P=0.061). Bone in-growth (or bone on-growth) fixation was obtained for all acetabular and femoral prostheses, with no hips of prosthesis displacement, periprosthetic osteolysis, or dislocation. Conclusion:Total hip arthroplasty for Crowe type IV DDH can achieve satisfactory clinical efficacy with similar functional recovery and rate of complication in extended trochanteric osteotomy and subtrochanteric shortening osteotomy. However, the extended greater trochanter osteotomy can reduce the operation time, blood loss and length of femoral shortening.

OBJECTIVE To obser ve the efficacy and safety of rimazo lom for painless gastroscopy sedation in outpatients. METHODS Totally 84 patients who underwent painless gastroscopy were collected from the outpatient department of the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from March to June in 2021. By random number table method combined with envelope allocation concealment method ，they were randomly divided into observation group and control group ，with 42 cases in each group. The patients in the observation group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+Rimazole toluenesulfonate for injection 0.2 mg/kg. Patients in the control group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+ Propofol emulsion injection 2 mg/kg. Gastroscopy was performed after the patient ’s consciousness disappeared. The sedative efficiency，sedative onset time ，recovery time and the occurrence of adverse drug reaction were observed in 2 groups. The heart rate（HR），mean arterial pressure （MAP），pulse oxygen saturation （SpO2），modified observer ’s assessment of alertness/sedation （MOAA/S）score and Narcotrend score were recorded in 2 groups after entering the room （T0），after anesthesia induction （T1）， when gastroscope entered the throat （T2），at the end of gastroscope withdrawal （T3），5 min after gastroscopy （T4）. RESULTS There was no significant difference in the effective rate of sedation （100％），the incidence of respiratory depression ， nausea and vomiting between the two groups （P＞0.05）. The qq.com onset time of sedation in the observation group was longer than control group ，and the recovery time and the incidence ofhypotension，hypotension to be tre ated，injection pain and bradycardia in observation group were significantly shorter or lower than control group （P＜0.05）. At T 0，there was no significant difference in HR ，MAP，SpO2，MOAA/S score or Narcotrend score between two groups （P＞0.05）. From T 1 to T 4，the HR of control group was significantly lower than that of the same group at T 0，and significantly lower than observation group at the same time（P＜0.05）. From T 1 to T 3，the MAP of two groups were significantly lower than the same group at T 0（P＜0.05），but there were no significant differences between two groups and between T 4 and T 0（P＞0.05）. There was no significant difference in SpO 2 at different time points between two groups and HR at different time points in observation group （P＞0.05）. From T 1 to T 3，MOAA/S score and Narcotrend score of two groups were significantly lower than the same group at T 0，while the MOAA/S score and Narcotrend score at T 1 and T 3 and Narcotrend score at T 3 of observation group were significantly higher than control group at the same time （P＜0.05），and the Narcotrend score of observation group at T 2 was significantly lower than control group at the same time（P＜0.05）；at T 4，there were no significant differences in MOAA/S score and Narcotrend score between two groups （P＞ 0.05）. CONCLUSIONS Remazolam shows good sedative effect and safety for painless gastroscopy.

Objective: To examine the independent and combined effects of pre-pregnancy BMI and gestational diabetes (GDM) on early adiposity rebound (AR) timing in children. Methods: Based on the "Ma'anshan Birth Cohort Study", 2 896 eligible maternal and infant pairs were recruited. In the cohort, we collected pre-pregnancy height, weight, 24 to 28 weeks GDM diagnosis, follow-up at 42 days, three months, six months, nine months of age, and every six months after one year of age, and continuously followed up to 6 years old, and obtained the child's length/height, weight, and other data. The intensity of the association between pre-pregnancy BMI, GDM, and early AR timing was analyzed by the multivariate logistic regression model. Multiplication and additive models were used to analyze how pre-pregnancy BMI and GDM influenced early AR timing in children. Results: The prevalence of underweight, average weight, overweight, and obesity before pregnancy were 23.2% (672), 66.4% (1 923), 8.7% (251), and 1.7% (50). The prevalence of GDM was 12.4%. We found that 39.3% of children had AR, and the average age at AR was (4.38±1.08). The results of multifactorial logistic regression analysis showed that pre-pregnancy overweight (OR=1.67,95%CI:1.27-2.19), pre-pregnancy obesity (OR=3.05,95%CI:1.66-5.56), and maternal GDM (OR=1.40,95%CI:1.11-1.76) were risk factors for early AR timing in children. In contrast, pre-pregnancy underweight (OR=0.60,95%CI:0.49-0.73) was a protective factor for early AR timing in children. Compared with the different effects of pre-pregnancy overweight/obesity and maternal GDM alone, the combined effect caused a higher risk of early AR timing in children, with OR values (95%CI) were 2.03 (1.20-3.44), 3.43 (1.06-11.12), respectively. The multiplication and additive models showed no interaction between pre-pregnancy BMI and GDM-influenced early AR timing in children. Conclusion: Higher pre-pregnancy BMI and maternal GDM are the independent risk factors for the early AR timing in children, and the co-occurrence of the two is higher risks, but there was no statistical interaction.
Child ; Infant ; Female ; Pregnancy ; Humans ; Adiposity ; Diabetes, Gestational/epidemiology* ; Overweight/epidemiology* ; Thinness ; Cohort Studies ; Body Mass Index ; Obesity