Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

This study established the mouse podocyte clone-5 (MPC5) with Smad3 knockout and studied the effect of transforming growth factor-beta 1 (TGF-β1) on the dedifferentiation of the MPC5 cells with Smad3 knockout, aiming to provide a cell tool for studying the role of Smad3 in mouse podocytes. The single-guide RNA (sgRNA) sequence targeting Smad3 was designed according to the principles of CRISPR/Cas9 design. The pX458-Smad3 vector was constructed and introduced into competent cells, and then the vector was extracted and used to transfect MPC5 cells. The successfully transfected cells were sorted by a flow cytometer. After single-cell clone expansion, PCR amplification of sequences adjacent to the edition site of Smad3 and sequencing were performed to identify potential cells with gene knockout. Western blotting was employed to verify the knockout efficiency of Smad3. Finally, the effect of Smad3 knockout on TGF-β1-induced dedifferentiation of MPC5 cells was analyzed by reverse transcription-polymerase chain reacting (RT-PCR), Western blotting, and the immunofluorescence method. The sgRNA was designed to target the fifth exon of Smad3. EGFP expression was observed 24 h after transfection of the pX458-Smad3 plasmid into MPC5 cells, with the transfection efficiency of 0.1% as determined by flow cytometry. From the transfected cells, 21 cell clones were obtained through flow cytometric sorting and single-cell clone expansion. PCR amplification and sequencing of the region around the sgRNA target site in Smad3 identified two cell clones with biallelic frameshift mutations. Western blotting results confirmed the absence of Smad3 expression in these clones, indicating successful establishment of the MPC5 cell line with Smad3 knockout. In normal MPC5 cells, TGF-β1 stimulation promoted the expression of fibrosis-related genes fibronectin and Col1a1 (collagen I) and inhibited the expression of the podocyte marker proteins synaptopodin and podocin, which suggested epithelial-mesenchymal transition and podocyte injury. However, in the two MPC5 cell lines with Smad3 knockout, TGF-β1-induced expression of epithelial-mesenchymal transition markers was significantly suppressed. The MPC5 cell lines with Smad3 knockout that were constructed by CRISPR/Cas9 provide a valuable cell model for functional studies of Smad3 protein and highlight the critical role of Smad3 in cell dedifferentiation.
Animals ; Smad3 Protein/genetics* ; CRISPR-Cas Systems/genetics* ; Mice ; Podocytes/metabolism* ; Transforming Growth Factor beta1/pharmacology* ; Cell Line ; Gene Knockout Techniques ; RNA, Guide, CRISPR-Cas Systems/genetics*

Objective To investigate the clinical efficacy of Qi Shi Shen Shu Capsule combined with dapagliflozin in treating type 2 diabetic nephropathy.Methods 120 patients with type 2 diabetic nephropathy(qi-yin liangxu syndrome)admitted to the endocrinology department in the inpatient and outpatient depart-ments of endocrinology from May 2022 to December 2023 were randomly divided into control and observation groups(60 cases each).The control group received dapagliflozin plus placebo capsules,while the observation group received dapagliflozin plus Qi Shi Shen Shu Capsule for 6 months.The therapeutic effects were observed between the two groups.Parameters including serum creatinine(Scr),urinary albumin-to-creatinine ratio(uACR),24-hour urinary protein quantification(24hUP),glycated hemoglobin(HbA1c),and tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and high sensitivity-C reactive protein(hs-CRP)were measured be-fore and after treatment.Results The total effective rate was higher(P＜0.05)in the observation group(93.33％)than in the control group(78.33％).After treatment,both groups showed decreased levels of uACR,Scr,24hUP,HbA1c,TNF-α,IL-6,and hs-CRP compared with baseline,with lower levels in the obser-vation group(P＜0.05).Conclusion Qi Shi Shen Shu Capsule combined with dapagliflozin can effectively re-duce uACR,Scr levels and serum inflammatory cytokines levels in patients with type 2 diabetic nephropathy.

This paper elaborated the structural principles,structures and working principles of the A5 type passive training system for hand function through discussed the clinical application of passive training system for hand function in the rehabilitation of patients with stroke.It analyzed a series of occurring common faults during system operation,such as system errors caused by missing components,improper sensitivity settings for spasticity,abnormal connections for equipment,motor failures,jam and pause of robotic hand,and faults of lifting table,and conducted fault analysis for them.After that,this paper proposed corresponding handling strategies and solutions for faults,which included software configuration,calibration and detection of robotic hand sensors,repair of connection fault,and regular maintenance and replacement of system's components.It provided theoretical basis for the maintenance and optimization of the passive training system for hand function.Thus,it can rapid remove troubles,and reduce the equipment's failure rate of passive training system for hand function,and improve the equipment's normal utilization rate,and ensure favorable performance of equipment in long-term use.

Objective To evaluate the quality of ketoconazole lotion produced by different domestic companies.Methods Legal standards and exploratory research were used to conduct a comprehensive evaluation of 45 batches(40 batch numbers)of ketoconazole lotion for national drug sampling inspection in 2024,including related substances,antioxidant content,packaging oxygen permeability,in vitro permeation test,and viscosity,antibacterial efficacy,irritation,microstructure,etc.Results The legal standard inspection pass rate was 100.0%.Correlation analysis found that the main factors affecting the quality of this product are prescription technology and packaging.Conclusion It is recommended that manufacturers optimize the prescription process as soon as possible,and pay attention to choose suitable packaging materials,effectively improve the quality of ketoconazole lotion.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

This paper elaborated the structural principles,structures and working principles of the A5 type passive training system for hand function through discussed the clinical application of passive training system for hand function in the rehabilitation of patients with stroke.It analyzed a series of occurring common faults during system operation,such as system errors caused by missing components,improper sensitivity settings for spasticity,abnormal connections for equipment,motor failures,jam and pause of robotic hand,and faults of lifting table,and conducted fault analysis for them.After that,this paper proposed corresponding handling strategies and solutions for faults,which included software configuration,calibration and detection of robotic hand sensors,repair of connection fault,and regular maintenance and replacement of system's components.It provided theoretical basis for the maintenance and optimization of the passive training system for hand function.Thus,it can rapid remove troubles,and reduce the equipment's failure rate of passive training system for hand function,and improve the equipment's normal utilization rate,and ensure favorable performance of equipment in long-term use.

Objective To evaluate the quality of ketoconazole lotion produced by different domestic companies.Methods Legal standards and exploratory research were used to conduct a comprehensive evaluation of 45 batches(40 batch numbers)of ketoconazole lotion for national drug sampling inspection in 2024,including related substances,antioxidant content,packaging oxygen permeability,in vitro permeation test,and viscosity,antibacterial efficacy,irritation,microstructure,etc.Results The legal standard inspection pass rate was 100.0%.Correlation analysis found that the main factors affecting the quality of this product are prescription technology and packaging.Conclusion It is recommended that manufacturers optimize the prescription process as soon as possible,and pay attention to choose suitable packaging materials,effectively improve the quality of ketoconazole lotion.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

Objective:To observe the changes of macular structure and microvessels in eyes with diabetes macular ischemia (DMI).Methods:A retrospective case study. From January 2023 to July 2023, 23 patients of 31 eyes diagnosed with DMI at Tangshan Ophthalmological Hospital were included in this study. Among them, there were 14 males with 23 eyes; Female cases with 8 eyes. Age were (59.5±4.6) years old. According to the DMI grading standard formulated by the research group for early treatment of diabetes retinopathy, the patients were divided into mild DMI group, moderate DMI group, and severe DMI group, with 8, 12, and 11 eyes respectively. The blood flow density (VD), perfusion area (FA), small vessel VD (SVD), inner retinal capillary plexus VD, FA, and outer retinal, choroidal, and ganglion cell complex (GCC) thickness within 1 mm of the macular fovea in retinal superficial vascular plexus (SVP)were measured using a scanning frequency light source optical coherence tomography instrument. The changes in macular structure and microvasculature in the affected eyes of different degrees of DMI groups were compared and observed. Inter group comparisons were conducted using one-way ANOVA or Kruskal Wallis H-test. Spearman correlation analysis was used to analyze the correlation between DMI severity and GCC, outer retina, choroid thickness, VD, FA and SVP VD, SVD and FA in inner retina. Results:The GCC ( F=70.670), outer retinal thickness ( H=12.393), VD ( F=105.506), SVD ( H=25.300), FA ( F=107.655), and VD ( H=24.098) and FA ( H=25.300) of the retinal SVP in the mild, moderate, and severe DMI groups were compared, and the differences were statistically significant ( P<0.05). There was no statistically significant difference in choroidal thickness ( H=2.441, P>0.05). Pairwise comparison between groups: VD, SVD, FA of GCC thickness and SVP, and VD of inner retina were statistically significant between severe DMI group and moderate DMI group, and between moderate DMI group and mild DMI group ( P<0.05). The thickness of outer retina was statistically significant between severe DMI group and moderate DMI group ( P<0.05). Inner retinal FA: there were statistically significant differences between severe DMI group, moderate DMI group and mild DMI group ( P<0.05). The correlation analysis results showed that GCC ( r s=-0.918), outer retinal thickness ( r s=-0.448), and inner retinal VD ( r s=-0.894) and FA ( r s=-0.918), as well as VD ( r s=-0.919), SVD ( r s=-0.924), and FA ( r s=-0.939) of retinal SVP, were all negatively correlated with the degree of DMI ( P<0.05). There was no correlation between choroidal thickness and degree of DMI ( r s=-0.081, P>0.05). Conclusion:The thickness of GCC, outer retina and choroid, the VD, SVD, and FA of the retinal SVP, the VD and FA of inner retina are all reduced in eyes with different degrees of DMI, while all of them are negatively correlated with the degree of DMI, except for choroid thickness.