Refractory acute T-lymphoblastic leukemia (T-ALL), which is characterized by a low sensitivity to conventional induction therapy and poor prognosis, poses significant challenges during treatment. This study reported a case of refractory T-ALL patient with mutations in the JAK1, JAK3, and STAT5B genes from Nanjing University’s Gulou Hospital. Following an unsuccessful course of standard VDLP regimen chemotherapy, the treatment was modified to include ruxolitinib in combination with venetoclax and azacitidine. Subsequent to this therapy, the patient achieved bone marrow minimal residual disease (MRD) negativity. Notably, pleural effusion and mediastinal mass significantly improved the post-chest cavity infusion of dexamethasone combined with etoposide at the same stage. The patient also underwent allogeneic hematopoietic stem cell transplantation upon achieving bone marrow remission and was followed up until January 2024. Ruxolitinib combined with venetoclax and azacytidine has shown promising efficacy and safety in treating refractory T-ALL harboring the JAK1, JAK3, and STAT5B mutations, providing a novel therapeutic approach for such patients.

ObjectiveTo explore the metabolic changes during the development of Tupaia belangeri breast tumors, to investigate the close relationship between the changes of serum metabolic substances and the occurrence and progression of tumors, and to screen for biomarkers reflecting the progression of breast tumors. MethodsBreast tumors in Tupaia belangeri were induced by orally administering 7,12-dimethylbenzoanthracene (DMBA) three times, with a 15-day interval between each administration, along with a high-fat and high-sugar diet. The DMBA-induced breast cancer group and the DMBA-inducedwithout breast cancer group were compared with the control group. Untargeted determination of serum metabolites was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) in DMBA-induced Tupaia belangeri with breast cancer, DMBA-induced without breast cancer and the control group. Multidimensional statistical analysis including unsupervised principal component analysis (PCA), and orthogonal partial least squares analysis (OPLS-DA) were conducted. Furthermore, t-test was used for intergroup differential comparison. Differential metabolites were screened under VIP>1 and P<0.05 conditions, and significantly changing differential metabolites were identified using the HMDB online database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was utilized to enrich metabolic-related gene regulatory pathways. ResultsThe incidence of breast tumors was 40% in DMBA-induced Tupaia belangeri. Compared with the control group, 30 metabolic differential products were detected in the serum of the group with breast cancer, with 18 down-regulated and 12 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in four metabolic pathways: glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism. Compared with the group without breast cancer, 18 metabolic differential products were detected, with 7 down-regulated and 11 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in the citric acid cycle and glutamate metabolism. Compared with the control group, 31 metabolic differential products were detected in the serum of the groups without breast cancer, with 14 down-regulated and 17 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in three metabolic pathways: glutamate metabolism, glyceride metabolism, and citric acid cycle. ConclusionMetabolomics analysis can reveal the characteristics of changes in metabolites in the serum of breast tumors. The results suggest that glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism pathways are associated with the occurrence and development of DMBA-induced breast tumors in Tupaia belangeri. It provides a foundation for further research into the biological mechanism of breast cancer.

Using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.

Objective:To assess the ultrasonographic features and potential diseases of fetal abnormal sylvian fissure(SF), and to explore the value of whole-genome sequencing (WGS) in prenatal detection.Methods:A total of 28 fetuses with a sonographic diagnosis of abnormal SF in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University between October 2018 and October 2020 were prospectively included. The fetal brain was evaluated by neuroultrasound and intrauterine MRI in detail. Amniotic fluid/cord blood obtained by amniocentesis or tissue samples from umbilical cord after birth were collected for WGS. Pregnancy outcomes and postnatal MRI were recorded, and neurodevelopment of live-born infants was followed up for more than 24 months after delivery.Results:During the study period, 28 fetuses with abnormal SF were identified, with a gestational age of 21.3-30.0 (24.8±2.0) weeks. Abnormal SF presented in MCD ( n=15, 53.6%), chromosomal anomalies ( n=3, 10.7%) or single-gene genetic syndromes ( n=3, 10.7%) with the affected fetuses showing developmental delay, hydrocephalus or leukomalacia ( n=4, 14.2%), corpus callosal agenesis with large interhemispheric cysts ( n=1, 3.6%), benign subarachnoid space enlargement with arachnoid cysts ( n=1, 3.6%), and multiple malformations ( n=1, 3.6%). Among the 15 cases with MCD, the most common pathology was lissencephaly/pachygyria, followed by schizencephaly, severe microcephaly, hemimegalencephaly with paraventricular heterotopia, and polymicrogyria. Abnormal SF presented bilaterally in 23 fetuses and unilaterally in 5. All cases were categorized into six types depending on SF morphology in the transthalamic section: no plateau-like or a small insula, linear type, irregular corrugated SF, Z-shaped, and cyst occupying type. In addition to abnormal SF, associated anomalies or mild variations were identified in all fetuses. There were 17 cases underwent intrauterine MRI, and 13 cases underwent postnatal MRI examination.And 25 pregnancies were terminated; 3 were born alive, and 2 had typical syndromic changes with poor neurodevelopmental prognosis. A related pathogenic genetic variant was detected in 57.1% (16/28) fetus, and the incidence of single nucleotide variants(SNVs) was 42.9% (12/28), among which de novo SNVs accounted for 91.7% (11/12). Conclusions:Fetal abnormal SF could be classified based on the ultrasonographic features of transthalamic section. Fetal abnormal SF may indicate MCD, some chromosomal abnormalities or single-gene genetic syndromes that may lead to poor neurodevelopmental outcomes, and may be affected by extra-cortical factors. It is suggested to carry out targeted prenatal genetic diagnosis for fetuses with abnormal SF.

Objective:To analyze the clinical characteristics of long-term survival patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with primary tumor radiotherapy, and to establish a Nomogram prognostic model, aiming to provide a certain reference for making a decision about the treatment of advanced NSCLC.Methods:A retrospective analysis was made on the data of 260 NSCLC patients who participated in two prospective clinical studies from January 2003 to May 2012 and the data of 138 NSCLC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from January 2014 to August 2020. The former 260 cases were used as a training set and the latter 138 cases were used as the validation set. The overall survival (OS) of ≥ 18 months was defined as long-term survival (LTS). The clinical characteristics of LTS patients were compared with those with OS less than 18 months. The clinical characteristics and treatment-related parameters between the two types of patients were compared using the χ2 test. A multivariate analysis was made using logistic regression, and a nomogram model was built using RStudio. Results:The median OS of the training set was 13.4 months (95% CI: 11.9-14.9), with 1-, 2-, and 3-year OS rates of 55.4%, 19.1%, and 11.9%, respectively. In the training set, 87 cases had LTS and were classified as the LTS group, while 173 cases had OS less than 18 months and were classified as the non-LTS group. The univariate analysis showed that the prognostic factors affecting LST included the KPS score, T status, the number of metastatic organs, the number of metastatic lesions, brain metastasis, bone metastasis, the number of chemotherapy cycles, the biologically effective dose (BED) to the primary tumor, hemoglobin level, platelet count, plasma D-dimer, fibrinogen level, lactate dehydrogenase, and lung immune prognostic index (LIPI; χ2=4.72-12.63, P < 0.05). The multivariable analysis showed that the independent prognostic factors of LTS included a number of chemotherapy cycles ≥ 4, BED ≥ 70 Gy, platelets ≤ 220×10 9/L, D-dimer ≤ 0.5 mg/L, and a good LIPI score ( P= 0.002, 0.036, 0.005, 0.008, and 0.002). A nomogram model was established using the meaningful parameters obtained in the multivariable analysis, determining that the training and validation sets had a consistency index (C-index) of 0.750 and 0.727, respectively. As shown by the analytical result of the corrected curves, for the advanced NSCLC patients treated with thoracic radiotherapy, their LTS probability predicted using the nomogram prognostic model was highly consistent with their actual LTS probability. Both the analytical result of the receiver operating characteristic (ROC) curves and the decision curve analysis (DCA) result showed that the composite prediction model was more beneficial than a single prediction model. Conclusions:For patients with advanced NSCLC treated with thoracic radiotherapy, the independent prognostic factors of LTS included the number of chemotherapy cycles, BED, platelet count, pre-chemotherapy D-dimer, and LIPI score. The Nomogram prognostic model built based on these prognostic factors is a convenient, intuitive, and personalized prediction model used to screen patients who can benefit from thoracic radiotherapy.

Humans ; Otitis Media, Suppurative ; Chronic Disease ; Biofilms ; Otitis Media

Objective:To study the relationship between endoplasmic reticulum stress (ERS) and apoptotic protein and myocardial pathological changes in rats after endostar combined with low-dose X-ray irradiation.Methods:Forty SD rats were evenly divided into four groups: control group (intraperitoneal injection of equal volume physiological saline, once per day, 14 d), endostar group (intraperitoneal injection of endostar 6 mg/kg, once per day, 14 d), irradiation group (15 Gy divided into 3 times X-ray irradiation) and combination group (intraperitoneal injection of endostar after irradiation at the same dose and time as the endostar group). At 1 and 6 months after treatment, myocardial tissues of rats were prepared for HE staining and Masson staining to observe the myocardial histological changes. TUNEL assay was used to detect myocardial cell apoptosis, and ImageJ software was utilized to calculate myocardial collagen volume fraction (CVF). The expression levels of ERS and apoptotic protein glucose-regulated protein 78 (GRP78), protein kinase-like endoplasmic reticulum kinases (PERK), CCAAT/enhancer binding protein homologous protein (CHOP) and cysteine-containing aspartate-specific protease-12 (Caspase-12) were detected by Western blot. One-way ANOVA was conducted using GraphPad Prism 8.0.1 software, and comparison between two groups was conducted using t-test. Results:At 6 months after treatment, the myocardial interstitium in the irradiation and combination groups was widened, showing strip-like or reticular fibrosis changes, and the myocardial interstitium had diffuse collagen fiber deposition. Compared with the control group, CVF was increased significantly (both P<0.01). At 1 and 6 months after treatment, the apoptotic index of myocardial cells in the combination group was significantly higher than that in the control group ( P<0.05, <0.001). At 1 and 6 months after treatment, the expression levels of GRP78 protein in the irradiation and combination groups were increased (all P<0.01), and the expression levels of PERK and CHOP proteins in the combination group were increased compared to those in the control group (both P<0.05). At 6 months after treatment, the expression levels of PERK and CHOP proteins in the irradiation group were increased compared to those in the control group (both P<0.05). Compared with the control group, Caspase-12 expression levels at 1 and 6 months after treatment were increased in the endostar, irradiation and combination groups (all P<0.05). Conclusions:The expression levels of ERS and apoptotic proteins are related to cardiac injury caused by irradiation in rats. After low-dose X-ray combined with endostar treatment, ERS is aggravated and myocardial apoptosis is increased.

Objective To explore the clinical efficacy and safety of betaquiline fumarate tablets in the treatment of multi drug resistant pulmonary tuberculosis.Methods Patients with multidrug-resistant tuberculosis(MDR-TB)admitted to the Third People's Hospital of Kunming from March 2019 to September 2022 were selected as the research objects.They were divided into two groups by random number table method.The observation group(n = 93)received anti tuberculosis treatment with a regimen containing bedaquiline fumarate tablets,while the control group(n = 90)received anti tuberculosis treatment with a regimen without bedaquiline fumarate tablets.The lesion absorption rate,sputum negative conversion rate,cavity reduction rate,treatment efficiency,and adverse drug reactions during treatment were collected at the end of 24 weeks.Results At the end of the 24th week of treatment,the differences between the observation group and the control group in the rates of lesion absorption rate(85.7%,63.3%),negative conversion of sputum smears(89.7%,71.4%),negative conversion of sputum cultures(82.1%,68.6%),cavity shrinkage rate(88.2%,69.4%),and total treatment efficacy(81.9%,60.2%)were statistically significant(P<0.05).The difference in the incidence of adverse drug reactions between the observation group and the control group(69.9%and 83.4%)was statistically significant(P<0.05),but the difference in the severity of adverse reactions was not statistically significant(P>0.05).Conclusion The regimen containing betaquiline fumarate tablets has good efficacy and is safe in the treatment of multidrug-resistant pulmonary tuberculosis.

Objective: Objective to investigate the health changes of patients with severe trimethyltin chloride (TMT) poisoning in four years. Methods: Six patients with severe TMT poisoning treated in the First Affiliated Hospital of Gannan Medical College in August 2016 were numbered 1, 2, 3, 4, 5 and 6 respectively. The patients were followed up 0.5, 2 and 4 years after poisoning and compared and analyzed. The follow-up contents include: symptom degree, score of simple mental intelligence examination scale (MMSE) and modified Rankin Scale (MRS) , cranial magnetic resonance imaging (MRI) , EEG, etc. Results: The symptoms of dizziness, headache, chest tightness, palpitation, nausea and vomiting decreased gradually in 6 patients. The symptoms of speech disorder and memory decline in No.1, 2 and 3 patients gradually increased, and the scores of MMSE and Mrs gradually decreased; Patients No.4, 5 and 6 had improved speech disorder, but their memory decreased, MMSE and Mrs scores were still flat, and mild cognitive impairment. The brain atrophy of No.1, 2 and 3 patients was aggravated, which showed obvious atrophy of hippocampus, temporal lobe, insular lobe and cerebellum and enlargement of ventricle; There was no significant change in brain atrophy in No.4, 5 and 6 patients. Conclusion: The neurotoxic symptoms in the later stage of severe TMT poisoning are still serious, and the neurotoxic time is long.
Atrophy ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Trimethyltin Compounds

Objective:To analyze the mediastinal displacement of target volume in the postoperative radiotherapy (PORT) process for non-small cell lung cancer (NSCLC) and the value of mid-term evaluation.Methods:For 100 patients with postoperativeN 2 stage NSCLC, R 1-2 and any N staging, bone anatomy was utilized to measure the change of the first and second CT localization on the same level. Statistical analysis were performed using the WilCoxon, Kruskal-Wallis and χ2 tests. The cut-off values were calculated with the receiver operating characteristic (ROC) curve. Results:Among the included patients, in the PORT process, the mediastinal displacement in the x (front and rear), Y (left and right) and Z (upper and lower) directions were 0.04-0.53 cm, 0.00-0.84 cm and 0.00-1.27 cm, respectively, and the order of mediastinal displacement distance wasz > Y> X,respectively. According to the ROC curve calculation, the cut-off values were 0.263, 0.352 and 0.405, respectively, which were greater than the cut-off values in 25 cases (25%), 30 cases (30%) and 30 cases (30%), respectively. There was significant difference in the three-dimensionalmediastinal displacement ( P=0.007, <0.001 and<0.001). The mediastinal displacement in thex, Y and Z directions had no statistical significance regarding resection site ( P=0.355, 0.239 and 0.256) and operation mode ( P=0.241, 0.110 and 0.064). Comparative analysis of modified whole group mediastinal shift> and cut-off values, medium-simulation (m-S) and the originally planned radiotherapy shown that there was no significant difference in the incidence of radiation esophagitis (RE) and radiation pneumonitis in PORT patients (all P>0.05); however, the incidence of ≥grade 3 RE in the modified plan after m-S was significantly lower than that in the originally planned PORT patients, which were 0 and 7%, respectively ( P<0.001). Conclusions:Mediastinal displacement exists in the PORT process of N 2 or/and R 1-2 cases after radical operation of NSCLC, and obvious movement occurs in 20%-30% of patients. Relocating and modifying the target volume and radiotherapy plan in the middle of the PORT process is beneficial to quality assurance and quality control.