OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

Lung transplantation is a key therapeutic approach for patients with end-stage lung diseases. Although its clinical outcomes have significantly improved, multidimensional injuries sustained by donor lungs during procurement, preservation, and transplantation remain major challenges affecting graft survival and long-term prognosis. This article proposes the "Guangzhou Classification" for full-course management of donor lung injury, characterized by spatiotemporal dynamics. Based on the progression of disease stages, donor lung injuries are systematically divided into three types: primary injuries (including donor ICU-related lung injury, pathogen colonization, and cold ischemia injury), secondary injuries (such as ventilator-induced lung injury after transplantation, ischemia-reperfusion inflammatory storm, and early rejection), and accompanying injuries (organ toxicity caused by accumulation of postoperative sedatives, analgesics, and vasoactive drugs). Drawing on previous studies and the clinical experience of our center, this paper elaborates the temporal evolution, key risk factors, and prevention and treatment strategies of each injury category, and discusses future research directions. By targeting critical injury factors at each stage, this classification aims to optimize both short-term and long-term outcomes of lung transplantation.

Tumor microenvironment(TME)includes inflammatory,metabolic,and immune microenvironment,which interact in a complex network,influencing tumorigenesis,progression,and metastasis.Clinical studies on traditional Chinese medicine(TCM)have found that dampness pathogen plays a significant role in gastrointestinal precancerous lesions,tumorigenesis,and metastasis.It disrupts the gastrointestinal tumor's inflammatory,metabolic,and immune microenvironments,promoting tumor development through various mechanisms.Based on the theory of dampness pathogen,it is proposed to eliminate dampness combined with detoxification to regulate tumor inflammatory microenvironment;invigorate qi,warm yang,and remove dampness to regulate metabolic microenvironment;and strengthen the spleen,support vital energy,and dispel dampness to improve immunosuppressive microenvironment.Treating gastrointestinal tumors from the perspective of dampness pathogen theory can offer new insights and focus areas for clinical diagnosis and treatment,as well as directions for research into the molecular mechanisms of compound Chinese herbal formulas.

Diabetic kidney disease （DKD） is a kidney disease caused by hyperglycemia，which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes，the incidence of DKD has also increased year by year，and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress，inflammation，renal fibrosis，and decreased mitophagy activity，which are developed under a variety of complex mechanisms. In traditional Chinese medicine，it is believed that the incidence of DKD is closely related to damp heat. Therefore，it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules （HKC） have the effect of clearing damp heat，detoxifying， and detumescence. Because of its unique curative effect on DKD，HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies，it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy，reducing mitochondrial damage，reducing renal fibrosis，controlling inflammatory response，and inhibiting oxidative stress，which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory，anti-oxidative stress，anti-renal fibrosis effects，as well as reduction of urinary protein. Since DKD is not a single injury of renal function，it is often accompanied by problems in blood pressure，blood lipids，blood circulation，body immunity， and other aspects. Therefore，the combination of HKC with other drugs can often achieve more comprehensive results，improve the advantages of various drugs，and improve the therapeutic effect. The combination of drugs such as antihypertensive，lipid-lowering， vascular circulation improvement，immunity inhibition，and anti-oxidative stress with HKC has achieved good results. In addition，HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress，but there are still many places worthy of further study，and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking，and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally，it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.

Diabetic kidney disease （DKD） is a kidney disease caused by hyperglycemia，which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes，the incidence of DKD has also increased year by year，and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress，inflammation，renal fibrosis，and decreased mitophagy activity，which are developed under a variety of complex mechanisms. In traditional Chinese medicine，it is believed that the incidence of DKD is closely related to damp heat. Therefore，it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules （HKC） have the effect of clearing damp heat，detoxifying， and detumescence. Because of its unique curative effect on DKD，HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies，it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy，reducing mitochondrial damage，reducing renal fibrosis，controlling inflammatory response，and inhibiting oxidative stress，which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory，anti-oxidative stress，anti-renal fibrosis effects，as well as reduction of urinary protein. Since DKD is not a single injury of renal function，it is often accompanied by problems in blood pressure，blood lipids，blood circulation，body immunity， and other aspects. Therefore，the combination of HKC with other drugs can often achieve more comprehensive results，improve the advantages of various drugs，and improve the therapeutic effect. The combination of drugs such as antihypertensive，lipid-lowering， vascular circulation improvement，immunity inhibition，and anti-oxidative stress with HKC has achieved good results. In addition，HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress，but there are still many places worthy of further study，and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking，and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally，it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.

Objective: To establish and identify hepatocyte-specific transmembrane protein 121 ( Tmem121 ) knockout mice． Methods: The hepatocyte-specific Tmem121 knockout mice ( Tmem121flox / flox / Cre，Tmem121ΔHep) were obtained by crossbreeding of Tmem121flox / + / Cre and Tmem121flox / flox mice，which were generated using the CRISPR / Cas9 and Cre / Loxp systems．The genotype was verified by PCR using genomic DNA extracted from mouse tails as template．The growth，reproduction and organ development of both control and knockout mice were ob- served and analyzed．PCR and Western blot methods were performed to assess the knockout efficiency of Tmem121 in mouse primary hepatocytes．CellMaskTM Deep Red plasma membrane staining was employed to compare the mor- phological differences in primary hepatocytes between control and knockout mice． Results: Tmem121flox / flox / Cre mice were successfully obtained according to genotype identification analysis，and there were no significant differ- ences between control and knockout mice in body mass，reproductive ability，growth and development of liver．The specific knockout of Tmem121 gene in primary hepatocytes did not significantly affect the morphological structure or pathological characteristics of liver tissue．However，compared to the control group，the levels of Tmem121 mRNA and protein in the primary hepatocytes of the knockout group were significantly reduced ( P ＜0. 01) ．CellMaskTM Deep Red plasma membrane staining indicated that the proportion of binucleated hepatocytes in Tmem121-deficient mice significantly increased ( P＜0. 05) ，while the cell area was significantly reduced ( P＜0. 001) ． Conclusion Hepatocyte-specific Tmem121 knockout mice are successfully constructed，which provides an animal model for further exploration of the function and mechanism of Tmem121 gene in liver diseases．

Objective:To compare the effects of different appointment regimens on the daily waiting time, fixedness of treatment time and lateness rate of radiotherapy patients.Methods:Medical records of 5488 radiotherapy from 332 patients on the same linear accelerator in West China Hospital of Sichuan University from March to June 2022 were selected. Based on the radiotherapy information integration platform of MOSAIQ, all patients were randomly assigned to the morning class, afternoon class and evening class. Traditional manual appointment regimen was adopted for the morning class, 30 min appointment regimen for the afternoon class, and 15 min appointment regimen for the evening class, respectively. The differences in patient waiting time for treatment, fixedness of treatment time, and lateness rate under different appointment regimens were compared. The fixedness of treatment time and waiting time was determined by one-way ANOVA, and the 2×3 Chi-square test was adopted for the lateness rate. Results:The waiting time in the 15 min appointment, the 30 min appointment and manual appointment groups were (27.08 ± 17.21), (34.57± 19.12) and (41.50 ±20.94) min, respectively. There was statistical significance among three appointment regimens ( F=254.97, P<0.001). The waiting time was the shortest in the 15 min appointment group, followed by the 30 min appointment group, and the manual appointment group (all P<0.001 for two-group comparison). The fixedness of treatment time in the 15 min appointment, the 30 min appointment and the manual appointment groups were (15.60±7.87), (18.69±8.94) and (24.30±15.10) min, respectively. There was statistical significance among three groups ( F=25.23, P<0.001). Among them, the fixedness of treatment time in the 15 min appointment group was the highest, followed by the 30 min appointment group, and the manual appointment group (all P<0.001). The lateness rates in the 15 min appointment, the 30 min appointment and the manual appointment groups were 5.7%, 6.2% and 9.6%, respectively. The lateness rate in the manual appointment group was higher than those in the 15 min appointment and the 30 min appointment groups ( χ2=19.24、14.90, both P<0.001), but there was no statistical significance in the lateness rate between the 15 min appointment and 30min appointment groups ( χ2=0.39, P=0.535). Conclusion:In the clinical practice of conventional intensity-modulated radiotherapy technology carried out by conventional linear accelerator, the 15 min appointment regimen can shorten the waiting time for radiotherapy and improve the fixedness of daily radiotherapy time, which is worthy of clinical promotion.

Tumor microenvironment(TME)includes inflammatory,metabolic,and immune microenvironment,which interact in a complex network,influencing tumorigenesis,progression,and metastasis.Clinical studies on traditional Chinese medicine(TCM)have found that dampness pathogen plays a significant role in gastrointestinal precancerous lesions,tumorigenesis,and metastasis.It disrupts the gastrointestinal tumor's inflammatory,metabolic,and immune microenvironments,promoting tumor development through various mechanisms.Based on the theory of dampness pathogen,it is proposed to eliminate dampness combined with detoxification to regulate tumor inflammatory microenvironment;invigorate qi,warm yang,and remove dampness to regulate metabolic microenvironment;and strengthen the spleen,support vital energy,and dispel dampness to improve immunosuppressive microenvironment.Treating gastrointestinal tumors from the perspective of dampness pathogen theory can offer new insights and focus areas for clinical diagnosis and treatment,as well as directions for research into the molecular mechanisms of compound Chinese herbal formulas.

Objective:To compare the effects of different appointment regimens on the daily waiting time, fixedness of treatment time and lateness rate of radiotherapy patients.Methods:Medical records of 5488 radiotherapy from 332 patients on the same linear accelerator in West China Hospital of Sichuan University from March to June 2022 were selected. Based on the radiotherapy information integration platform of MOSAIQ, all patients were randomly assigned to the morning class, afternoon class and evening class. Traditional manual appointment regimen was adopted for the morning class, 30 min appointment regimen for the afternoon class, and 15 min appointment regimen for the evening class, respectively. The differences in patient waiting time for treatment, fixedness of treatment time, and lateness rate under different appointment regimens were compared. The fixedness of treatment time and waiting time was determined by one-way ANOVA, and the 2×3 Chi-square test was adopted for the lateness rate. Results:The waiting time in the 15 min appointment, the 30 min appointment and manual appointment groups were (27.08 ± 17.21), (34.57± 19.12) and (41.50 ±20.94) min, respectively. There was statistical significance among three appointment regimens ( F=254.97, P<0.001). The waiting time was the shortest in the 15 min appointment group, followed by the 30 min appointment group, and the manual appointment group (all P<0.001 for two-group comparison). The fixedness of treatment time in the 15 min appointment, the 30 min appointment and the manual appointment groups were (15.60±7.87), (18.69±8.94) and (24.30±15.10) min, respectively. There was statistical significance among three groups ( F=25.23, P<0.001). Among them, the fixedness of treatment time in the 15 min appointment group was the highest, followed by the 30 min appointment group, and the manual appointment group (all P<0.001). The lateness rates in the 15 min appointment, the 30 min appointment and the manual appointment groups were 5.7%, 6.2% and 9.6%, respectively. The lateness rate in the manual appointment group was higher than those in the 15 min appointment and the 30 min appointment groups ( χ2=19.24、14.90, both P<0.001), but there was no statistical significance in the lateness rate between the 15 min appointment and 30min appointment groups ( χ2=0.39, P=0.535). Conclusion:In the clinical practice of conventional intensity-modulated radiotherapy technology carried out by conventional linear accelerator, the 15 min appointment regimen can shorten the waiting time for radiotherapy and improve the fixedness of daily radiotherapy time, which is worthy of clinical promotion.

Lung transplantation is a key therapeutic approach for patients with end-stage lung diseases. Although its clinical outcomes have significantly improved, multidimensional injuries sustained by donor lungs during procurement, preservation, and transplantation remain major challenges affecting graft survival and long-term prognosis. This article proposes the "Guangzhou Classification" for full-course management of donor lung injury, characterized by spatiotemporal dynamics. Based on the progression of disease stages, donor lung injuries are systematically divided into three types: primary injuries (including donor ICU-related lung injury, pathogen colonization, and cold ischemia injury), secondary injuries (such as ventilator-induced lung injury after transplantation, ischemia-reperfusion inflammatory storm, and early rejection), and accompanying injuries (organ toxicity caused by accumulation of postoperative sedatives, analgesics, and vasoactive drugs). Drawing on previous studies and the clinical experience of our center, this paper elaborates the temporal evolution, key risk factors, and prevention and treatment strategies of each injury category, and discusses future research directions. By targeting critical injury factors at each stage, this classification aims to optimize both short-term and long-term outcomes of lung transplantation.