Objective:To establish an identical UPLC-MS/MS method for determination of related substances of 15 drugs(bezafibrate,acipimox,gliquidone,glimepiride,glipizide,glibenclamide,enalapril,captopril,irbesartan,amlodipine,felodipine,nimodipine,nitrendipine,nisoldipine,nifedipine).Methods:The chromatography was performed on Waters ACQUITY UPLCHSS T3(2.1 mm × 100 mm,1.8 μm)column,mobile phase was 0.01 mmol·L-1 Ammonium formate solution containing 0.1％formic acid and methanol with gradient elution.The flow rate was 0.3 mL·min-1,and the injection volume was 2 μL.The detection was carried out by electrospray ioniza-tion(ESI).Multiple-reaction monitoring(MRM)was employed with switching electrospray ion source polarity in positive and negative mode.Results:The 21 related substances showed good linearity(r ≥0.998 35)in the tested ranges.The precision(RS D≤3.45％)and stability(RSD≤3.48％)of the method were good for the related sub-stances.The average recoveries of the related substances were in the range of 91.81％-101.84％with relative standard deviations RSD≤4.66％.Conclusion:The method is rapid,simple,accurate and highly sensitive,and can be used as a auxiliary test method and confirmatory method for current drug standards.

On 25th September 2021, a patient was admitted in the Department of Hand Microsurgery, Chongqing Great Wall Orthopaedic Hospital with an infectious proximal tibia defect and soft tissue defect after the resection of a giant cell tumour of tendon sheath (GCTTS). After relevant examinations, it was found that there was a large bone defect at proximal medial tibia, with an extremely thin of medial tibial plateau. Size of bone defect was 8.0 cm×3.5 cm×3.0 cm, and soft tissue defect was 6.0 cm×8.0 cm. A phased surgery was planned: firstly, the internal fixation was removed with thorough debridement and then the cavity was filled by antibiotic bone cement for control of the infection; In the phase-Ⅱ surgery, a series of anterolateral thigh myocutaneous flap (the volume of the muscle flap was 6.0 cm×2.5 cm×2.0 cm, and the size of flap was 4.0 cm×9.0 cm) and an iliac bone flap were used and the cavity of medial proximal tibia was filled with calcium sulphate and anterolateral thigh muscle graft. A piece of iliac bone graft was transferred to support the tibial plateau, and the wound was covered by flap (the volume of the iliac bone fragment was 12.0 cm×5.0 cm×2.0 cm, and the size of flap was 4.0 cm×9.0 cm). At 3 years of postoperative follow-up, the fracture healed well, the cavity at medial proximal tibia was significantly reduced. Appearance of flaps was good with restored protective sensation. Function of the affected knee was close to normal with a score of 94 according to Lysholm Knee Scale.

On 25th September 2021, a patient was admitted in the Department of Hand Microsurgery, Chongqing Great Wall Orthopaedic Hospital with an infectious proximal tibia defect and soft tissue defect after the resection of a giant cell tumour of tendon sheath (GCTTS). After relevant examinations, it was found that there was a large bone defect at proximal medial tibia, with an extremely thin of medial tibial plateau. Size of bone defect was 8.0 cm×3.5 cm×3.0 cm, and soft tissue defect was 6.0 cm×8.0 cm. A phased surgery was planned: firstly, the internal fixation was removed with thorough debridement and then the cavity was filled by antibiotic bone cement for control of the infection; In the phase-Ⅱ surgery, a series of anterolateral thigh myocutaneous flap (the volume of the muscle flap was 6.0 cm×2.5 cm×2.0 cm, and the size of flap was 4.0 cm×9.0 cm) and an iliac bone flap were used and the cavity of medial proximal tibia was filled with calcium sulphate and anterolateral thigh muscle graft. A piece of iliac bone graft was transferred to support the tibial plateau, and the wound was covered by flap (the volume of the iliac bone fragment was 12.0 cm×5.0 cm×2.0 cm, and the size of flap was 4.0 cm×9.0 cm). At 3 years of postoperative follow-up, the fracture healed well, the cavity at medial proximal tibia was significantly reduced. Appearance of flaps was good with restored protective sensation. Function of the affected knee was close to normal with a score of 94 according to Lysholm Knee Scale.

Objective:To establish an identical UPLC-MS/MS method for determination of related substances of 15 drugs(bezafibrate,acipimox,gliquidone,glimepiride,glipizide,glibenclamide,enalapril,captopril,irbesartan,amlodipine,felodipine,nimodipine,nitrendipine,nisoldipine,nifedipine).Methods:The chromatography was performed on Waters ACQUITY UPLCHSS T3(2.1 mm × 100 mm,1.8 μm)column,mobile phase was 0.01 mmol·L-1 Ammonium formate solution containing 0.1％formic acid and methanol with gradient elution.The flow rate was 0.3 mL·min-1,and the injection volume was 2 μL.The detection was carried out by electrospray ioniza-tion(ESI).Multiple-reaction monitoring(MRM)was employed with switching electrospray ion source polarity in positive and negative mode.Results:The 21 related substances showed good linearity(r ≥0.998 35)in the tested ranges.The precision(RS D≤3.45％)and stability(RSD≤3.48％)of the method were good for the related sub-stances.The average recoveries of the related substances were in the range of 91.81％-101.84％with relative standard deviations RSD≤4.66％.Conclusion:The method is rapid,simple,accurate and highly sensitive,and can be used as a auxiliary test method and confirmatory method for current drug standards.

Objective:To investigate optimal treatment strategy for pT3N0 laryngeal squamous cell carcinoma（SCC）. Methods:A retrospective study of 150 patients with pT3N0 laryngeal SCC treated in the First Affiliated Hospital of Chongqing Medical University was performed. The efficacies of partial laryngectomy and total laryngectomy, as well as surgery alone and postoperative radiotherapy were evaluated. The overall survival（OS）, disease specific survival（DSS） and disease-free survival（DFS） were analyzed with statistical package from SPSS. Results:Among the 108 patients with glottic laryngeal SCC, there were no significant differences in OS, DSS and DFS between the partial laryngectomy group and the total laryngectomy group（Log-rank=0.184, 0.010 and 0.051, P>0.05）. Similarly, there were no significant differences in OS, DSS and DFS between the surgery-alone group and postoperative radiotherapy group（Log-rank=0.214, 0.251 and 0.003, P>0.05）. Among the 38 patients with supraglottic laryngeal SCC, the OS in the total laryngectomy group was significantly higher than that in the partial laryngectomy group（Log-rank=7.338, P=0.007）. The DSS and DFS in the total laryngectomy group were higher than in the partial laryngectomy group, but the differences were not statistically significant（Log-rank=0.895 and 1.792; P>0.05）. The DFS in the postoperative radiotherapy group was significantly higher than in the surgery-alone group（Log-rank=7.172, P=0.007）, but there were no significant differences in OS and DSS between these two groups（Log-rank=0.010 and 0.876, P>0.05）. Conclusion:For pT3N0 glottic laryngeal cancer patients, the efficacy of partial laryngectomy is comparable to total laryngectomy, same as surgery alone and postoperative radiotherapy. For pT3N0 supraglottic laryngeal cancer patients, total laryngectomy could improve the overall survival, and postoperative radiotherapy could reduce the recurrence. Prospectively randomized study with large samples is still needed.
Humans ; Laryngeal Neoplasms/therapy* ; Laryngectomy/methods* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Male ; Female ; Middle Aged ; Disease-Free Survival ; Neoplasm Staging ; Aged ; Survival Rate ; Treatment Outcome

Antibiotic-resistant (AR) bacterial wound infections (WIs) impose major burdens on healthcare systems, exacerbated by ineffective therapies and stalled antibiotic development. Phage therapy and phage-derived enzymes have gained traction as potent alternatives, leveraging targeted bactericidal mechanisms to combat AR pathogens. In this review, we summarised the antimicrobial mechanisms of both phage therapy and phage-derived enzymes as antimicrobial therapy, and outlined recent advances in their use for in vitro , in vivo and clinical applications for WI management. In addition, we also highlights recent advancements in their development, driven by genetic engineering, chemical modifications, and artificial intelligence. Finally, we identified the potential barriers and challenges they may encounter in clinical practice and the corresponding strategies to address these issues. The entire review gives us a comprehensive understanding of the latest advances in phages and their derivative enzyme therapies for treating WIs, in the hope that research in this field will continue to improve and innovate, accelerating the transition from the laboratory to application at the bedside and ultimately improving the efficacy of treatment for AR bacterial WIs.
Humans ; Phage Therapy/methods* ; Wound Infection/drug therapy* ; Bacteriophages/enzymology* ; Enzyme Therapy/methods* ; Animals ; Bacterial Infections/therapy*

Purpose: Achieving high-quality immune reconstitution (IR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is directly associated with the patient’s ability to resist infections, prevent tumor relapses, and suppress graft-versus-host disease (GVHD). The status of CD4 + T cells is critical for reconstituting adaptive immunity after transplantation; however, the patterns of reconstitution and their influencing factors remain unclear. Methods: This retrospective cohort study involved 164 patients who underwent myeloablative allo-HSCT from April 2016 to May 2023. Based on the early post-transplantation CD4 + T cell counts, the cohort was divided into two groups: 73 patients with high-quality IR (HIR) and 34 patients with low-quality IR (LIR). LIR was associated with an increased risk of Epstein–Barr virus (EBV) reactivation following transplantation. Plasma EBV viral load was monitored weekly using quantitative PCR for the first 100 days post-transplantation. Results: The LIR group had a higher viral load at the time of the first EBV reactivation and a significantly earlier first reactivation compared to the HIR group. No significant differences were observed in overall survival, GVHD incidence, or relapse rates between the groups. A CD4 + T cell count of < 60 cells/μL within 30 days post-transplantation was associated with a higher incidence of EBV viremia compared to the control group. Conclusion These findings suggest that early CD4 + T cell counts may serve as a predictive marker for post-transplant EBV infection.

BackgroundSibling relationships play a critical role in shaping anxiety symptoms in firstborn children. Anxiety symptoms often originate in early childhood and can persist into adolescence and adulthood. However， there is insufficient research on anxiety symptoms in preschool children， especially firstborn preschool children. ObjectiveTo explore the influencing factors of anxiety symptoms among firstborn preschool children， so as to provide references for the intervention of anxiety symptom for children in families with multiple children. MethodsFrom October to December 2021， a total of 8 449 children from 234 kindergartens in Longhua District of Shenzhen were included using a cluster sampling method. Sibling Inventory of Behavior （SIB） and Spence Preschool Anxiety Scale （SPAS） were used to investigate. Logistic regression analysis was used to identify influencing factors of anxiety symptoms in firstborn preschool children. ResultsA total of 8 419 （99.64%） valid questionnaires were collected. Anxiety symptoms were detected in 344（4.09%） firstborn preschool children. Statistically significant differences were observed between anxiety group and non-anxiety group in terms of household registration， monthly family income， maternal age， maternal education level， paternal education level， family living conditions and whether they are left-behind children （χ²/t=9.906， 33.490， 5.136， 13.485， 9.690， 17.332， 21.975， P<0.05 or 0.01）. Compared with non-anxiety group， children in the anxiety group scored higher on the SIB dimensions of rivalry， aggression and avoidance （t=165.322， 74.471， 286.419， P<0.01）， and lower on companionship， empathy and teaching （t=59.133， 42.417， 39.112， P<0.01）. Risk factors for anxiety symptoms in firstborn preschool children included left-behind children， as well as negative sibling relationships characterized by rivalry and avoidance （OR=1.195， 1.143， 1.260， P<0.05 or 0.01）. ConclusionFirstborn preschool children who are left-behind are more susceptible to anxiety symptoms. Negative sibling relationships， characterized by competition and avoidance， may also contribute to the emergence of anxiety symptoms in firstborn preschool children.

Objective To analyze the positive rate of serum mycoplasma pneumoniae antibody IgM in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Liangjiang New Area of Chongqing and the related risk factors, so as to provide a theoretical basis for clinical diagnosis and treatment of AECOPD. Methods Retrospective analysis of 728 cases of AECOPD patients from January 2020 to December 2021 in Chongqing Liangjiang New Area Third Class Hospital. ELISA was used to determine Mycoplasma pneumoniae IgM antibodies. According to the detection of Mycoplasma pneumoniae IgM antibodies, the patients were divided into infection group and non-MP infection group. Clinical data such as gender, age, length of stay, place of residence, smoking status, home oxygen therapy, GOLD grade of COPD, number of acute exacerbations in the previous year, mechanical ventilation, and application of anti-infective drugs were collected. Univariate analysis and logistic regression were used to analyze the risk factors of MP infection in AECOPD patients. Results The positive rate of MP-IgM in 728 AECOPD patients was 15.38% (112/728), including 67 males and 45 females. There was no significant difference in the positive rate of MP-IgM in AECOPD patients between different seasons (χ²=2.840, P>0.05). Age ≥60 (OR=3.243), smoking (OR=2.559) and GOLD grade 3-4 (OR=3.760) were independent risk factors for MP infection in AECOPD patients. Conclusion The incidence of MP infection in AECOPD patients in Liangjiang New Area of Chongqing is relatively high, especially in AECOPD patients with age ≥ 60, smoking, GOLD grade 3-4, which should be warned of the possibility of mycoplasma pneumoniae infection , and targeted treatment measures can improve the cure rate.

BACKGROUND: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. METHODS: ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. RESULTS: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. CONCLUSIONS Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.