Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To explore the effects of transcutaneous electrical acupoint stimulation(TEAS)combined with multi-model analgesia on infrared thermal imaging characteristics and pain after total knee arthroplasty(TKA).Methods A total of 74 patients with TKA were divided into the treatment group and the control group according to random number table method,with 37 cases in each group.The control group was treated with multi-model analgesia,and the treatment group was treated with TEAS on the basis of multi-model analgesia for 30 min,once in the morning and afternoon before the patient's rehabilitation exercise 1-7 days after surgery.The infrared thermal imaging data,visual analogue scale(VAS)score,Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score and pain threshold of the two groups were recorded and analyzed before and at different time points after operation.Results There were 2 cases dropped out in each group.Compared with before surgery,both groups had an increase in knee joint temperature on the surgical side 14 days after surgery(P<0.05),and the temperature in the treatment group was lower than that in the control group(P<0.05).The self knee temperature difference in the treatment group was lower than that in the control group 14 days after surgery(P<0.05).Compared with before surgery,the VAS score of the treatment group decreased 3 and 7 days after surgery(P<0.05),while the VAS score of the control group decreased 7 days after surgery(P<0.05);compared with the control group at 3 and 7 days after surgey,the VAS score of the treatment group was lower than that of the control group.Compared with before surgery,the WOMAC scores of both groups increased 7 days after surgery(P<0.05);after 7 days of surgery,the WOMAC score of the treatment group was lower than that of the control group(P<0.05).Compared with before surgery,the pain threshold values of both groups increased 7 days after surgery(P<0.05);compared with the control group at 3 and 7 days after surgery,the pain threshold values of the treatment group was higher than that of the control group(P<0.05).Conclusion TEAS combined with multi-model analgesia can reduce the temperature of the knee joint,relieve the pain of the operated limb,and promote the early functional recovery of the knee joint after TKA.Infrared thermal imaging technology has a certain application value in indirectly assessing the degree of postoperative pain and detecting early infection of the affected limb.

Objective To explore the treatment effects and mechanism of Fangji Huangqi Xiaozhong Prescription in metabolic syndrome phenotype osteoarthritis(MS-OA)based on PPARγ/NF-κB signaling pathway.Methods SD rats were randomly divided into sham-operation group,OA group,MS-OA group,Western medicine group,and TCM high-and low-dasage groups.The modified Hulth method was used to make the OA model,and OA model was added with high-carbohydrate high-fat diet to make the MS-OA model.TCM high-and low-dosage groups were given 15.12,7.56 g/kg Fangji Huangqi Xiaozhong Prescription for gavage.The Western medicine group was given 16.2 mg/kg of losoprofen sodium by gavage,while the other groups were given physiological saline by gavage once a day for 6 consecutive weeks.Rat body mass was measured,biochemical detection of blood lipids and blood glucose was conducted,ELISA was used to detect the contents of serum TNF-α,IL-1β,IL-10 and leptin,morphological changes in cartilage tissue were observed using safranin O-fixed green and HE staining,immunohistochemical staining was used to detect expressions of Acan,ColⅩ,MMP13,TNF-α,IL-1β and PPARγ in cartilage tissue,Western blot was used to detected the expression of PPARγ,NF-κBp65 and p-NF-κBp65 protein in cartilage tissue.Results Compared with the sham-operation group,body mass and serum TC,TG,LDL-C,TNF-α,IL-1β and leptin of MS-OA group increased significantly(P<0.01),the contents of HDL-C and IL-10 decreased(P<0.01),cartilage tissue degeneration was significant,and the Mankin score increased(P<0.01),the expression of ColⅩ,MMP13,TNF-α,IL-1β,p-NF-κBp65 protein increased(P<0.05,P<0.01),and the expression of Acan and PPARγ protein decreased(P<0.01).Compared with the MS-OA group,the contents of serum TC,TG,LDL-C,TNF-α and leptin decreased in TCM high-dosage group(P<0.05,P<0.01),the content of IL-10 increased(P<0.05),the pathological damage of cartilage tissue improved,the Mankin score decreased(P<0.01),the expressions of ColⅩ,MMP13,TNF-α,IL-1β and p-NF-κBp65 protein in cartilage tissue decreased(P<0.05,P<0.01),and the protein expressions of Acan and PPARγ protein increased(P<0.01,P<0.05).Conclusion Fangji Huangqi Xiaozhong Prescription can improve lipid metabolism disorder,improve intra-articular inflammatory environment,balance cartilage metabolism,and delay cartilage degeneration in MS-OA rats.Its mechanism may be related to the regulation of PPARγ/NF-κB signaling pathway.

Objective To evaluate the value of miniprobe endoscopic ultrasound(EUS)in guiding endoscopic treatment of small-diameter(maximum diameter less than 1 cm)and low-grade(G1 grade)rectum neuroendocrine neoplasm(R-NEN),and to provide evidence and clues for its clinical application and further research.Methods The clinical data of 85 cases of low-grade(G1 grade)R-NEN with a maximum diameter of less than 1 cm who underwent endoscopic treatment in our center from January 2014 to December 2020 were retrospectively analyzed.The patients were divided into the EUS group(37 cases)and control group(48 cases)according to whether EUS was performed before endoscopic treatment.The positive rate of incision margin,the incidence of complications,the recurrence rate,the hospital stay,the cost of hospitalization and endoscopic therapy were compared between the two groups.Results The positive rate of incision margin in the EUS group was significantly lower than that in control group(P<0.05).There was no significant difference in the incidence of complications,tumor recurrence rate,hospital stay or hospital costs between the two groups(P>0.05).There was statistically significant difference in the endoscopic therapy between the two groups(P<0.05).Conclusion Evaluating the lesion depth of small-diameter and low-grade(G1 grade)R-NEN before surgery by miniprobe EUS and selecting endoscopic surgery according to its results of can significantly reduce the residual risk of resection margin tumors.

Background Some studies have found that exposure to heavy metals significantly increases the risk of nonalcoholic fatty liver disease (NAFLD), and welding operators in automobile manufacturing enterprises are exposed to heavy metals in the working environment. Objective To analyze the prevalence and related factors of NAFLD in workers of an automobile company in Guangzhou. Methods From January 1 of 2023 to December 31 of 2023, 5463 workers of an automobile company in Guangzhou who participated in the physical examination in the Occupational Health Surveillance Centre of Guangzhou Occupational Disease Prevention and Treatment Hospital were selected as research subjects. The general data, laboratory examinations, B-ultrasound examinations, and other data of the subjects were obtained through the physical examination system. The exposed occupational hazards were identified based on the workplace hazard surveillance report provided by the automotive company. Logistic regression was used to analyze potential influencing factors of NAFLD, and stratified analysis was used to adjust confounding factors according to the stepwise model to evaluate the relationship between exposure to manganese and its inorganic compounds and NAFLD. Results A total of 2129 cases (38.97%) were reported positive NAFLD. The results of logistic regression analysis showed that women had a lower risk of NAFLD (OR=0.40, 95%CI: 0.25, 0.64), while age > 25 years old (OR=1.49, 95%CI: 1.39, 1.60), body mass index (BMI) ≥24 kg·m⁻² (OR=7.54, 95%CI: 6.46, 8.79), and elevated alanine aminotransferase (ALT) (OR=4.87, 95%CI: 3.73, 6.36), γ-glutamyl transpeptidase (γ-GGT) (OR=1.54, 95%CI: 1.17, 2.02), triglyceride (TG) (OR=3.47, 95%CI: 2.92, 4.14), and fasting blood glucose (OR=1.70, 95%CI: 1.32, 2.20) associated with a higher risk of NAFLD. NAFLD was positive in 39.40% of heavy metal exposed workers (701/1779). NAFLD was positive in 45.19% of workers exposed to manganese and its inorganic compounds (169/374), and among workers over 34 years old, exposure to manganese and its inorganic compounds (OR=1.79, 95%CI: 1.07, 2.97) significantly increased the prevalence of NAFLD. Conclusion The association between heavy metal exposure and NAFLD in workers of an automobile enterprise in Guangzhou is not significant, but age and gender are related to the prevalence of NAFLD. BMI, ALT, γ-GGT, TG, and fasting blood glucose are positively correlated with the prevalence of NAFLD. Exposure to manganese and its inorganic compounds in welding workers of the automobile enterprise is associated with elevated risk of the disease, and the prevalence of NAFLD is significantly increased in workers over 34 years old.

RNA fluorescence aptamers are RNA sequences that can specifically bind to non-toxic,cell permeable,and self-fluorescent target molecules and activate their luminescent properties.These aptamers provide powerful tools for biosensing and imaging researches due to their simple structure,easy synthesis,and easy transfection.This article summarized the characteristics and development history of various RNA fluorescent aptamers,including Malachite Green,Spinach,Broccoli,Mango,Corn,and Pepper family,as well as their corresponding fluorescent groups.The applications of RNA fluorescent aptamers were also reviewed from two aspects:extracellular detection and cell imaging.This review might provide guidance for labeling,detection and interactions of molecules from proof of concept and clinical assessment to practical clinical and biomedical applications.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male ; Child ; Female ; Humans ; Child, Preschool ; Receptors, Tumor Necrosis Factor, Type I/genetics* ; Retrospective Studies ; Hereditary Autoinflammatory Diseases/drug therapy* ; Glucocorticoids/therapeutic use* ; Biological Factors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Autoantibodies ; Familial Mediterranean Fever/diagnosis* ; Mutation

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*