Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Background and Purpose:Previous studies have investigated the prognostic significance of skeletal muscle and adipose tissue composition and distribution in colorectal cancer patients,yet most have not differentiated between rectal and colon cancer patient cohorts.This study aimed to explore the relationship between body composition and long-term prognosis,and to develop a postoperative predictive model.Methods:Clinical data of rectal cancer patients who underwent surgical treatment at Qingdao University Affiliated Hospital from January 2018 to December 2021 were retrospectively collected.Inclusion criteria:①Age＞18 years;② Preoperative colonoscopy and pathological diagnosis of colorectal cancer;③ Complete surgical resection;④Abdominal computed tomography(CT)scan 1 month before surgery.Exclusion criteria:① Clinical data is missing;② Multiple metastases of tumors;③ Tumor T stage 0 or carcinoma in situ;④ Severe artifacts lead to poor quality CT imaging,making it difficult to distinguish between fat and muscle;⑤ Inability to obtain follow-up results.This study has been approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University(approval number:QYFYWZLL30313),and informed consent has been waived in the ethical approval process.The skeletal muscle index(SMI)and subcutaneous adipose tissue index(SATI)were calculated by dividing the areas of skeletal muscle and subcutaneous fat observed on CT scans by the square of the patient's height.Univariate and multivariate COX regression analyses were conducted to identify risk factors influencing recurrence-free survival(RFS)and overall survival(OS)in rectal cancer patients.Based on the results of the multivariate analysis,a nomogram prediction model was developed,its predictive power and accuracy were assessed using the receiver operating characteristic(ROC)curve,calibration plots and decision curve analysis(DCA),and internal validation was conducted.Results:A total of 696 patients were included in this study,with 96(13.8%)patients experiencing postoperative recurrence and 89(12.8%)patients dying.Multivariate COX regression analysis showed that SMI,SATI,tumor T stage and N stage were independent factors affecting the postoperative RFS and OS of patients.Nomogram prediction models for RFS and OS in rectal cancer patients were constructed based on the above independent predictors.The area under ROC curve(AUC)for 3-,4-and 5-year RFS was 0.862,0.846 and 0.824,respectively;the AUC for 3-,4-and 5-year OS was 0.886,0.898 and 0.875,respectively.The models were evaluated using calibration curves and decision curves,and internal validation was performed,which showed that the prediction accuracy of the models was good.Conclusion:CT body composition is an independent predictor of RFS and OS in rectal cancer patients,and the nomogram model developed based on these factors demonstrates good predictive value for patient prognosis.

Objective:? To summarize the achievements in improving the consistency of clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing results.Methods:? From 2021 to 2024, Zhongshan Hospital Affiliated to Fudan University recruited laboratories voluntarily participating in the MSHP (Clinical LC-MS/MS Testing Consistency Program). As of Batch 202404, a total of 76 laboratories had enrolled, including 60 medical institutions (all tertiary hospitals) and 16 third-party laboratories. Test items were established, and comparative samples were distributed regularly-each item′s samples covered three concentrations (high, medium, and low). Samples were shipped via cold chain and tested within one week. Our laboratory′s measurements served as the target, with participating labs′ results within ±25% of the target deemed qualified. Passing-Bablok regression and Bland-Altman analysis were used to assess consistency.Results:Taking 3-MT (3-methoxytyramine) as an example, the coefficients of variation (CVs) for the project′s three concentration levels improved from 17.00%, 47.18%, and 4.88% in the first comparative batch to 9.59%, 9.59%, and 6.1% in Batch 202404. Passing-Bablok regression results for the 5 units participating in 3-MT testing showed that Laboratory A had proportional bias but no systematic bias (regression slope [95% CI]: 0.903 [0.862-0.952]; intercept [95% CI]: 0.912 [-1.921-6.073]). The remaining laboratories exhibited no proportional or systematic bias with the target (Laboratory B: slope 1.031 [0.961-1.147], intercept-0.733 [-4.641-8.272]; Laboratory C: slope 0.982 [0.940-1.009], intercept-0.576 [-2.675-1.891]; Laboratory D: slope 0.973 [0.939-1.066], intercept-1.168 [-6.108-1.649]; Laboratory E: slope 0.999 [0.905-1.051], intercept-1.876 [-6.111-3.508]). Bland-Altman analysis indicated that all 5 laboratories′ results generally showed good consistency with the target. Through quality feedback and optimizing sample preparation concentrations, result consistency was enhanced.? Conclusion:? Clinical LC-MS/MS testing consistency programs contribute to improving the comparability of test results.

Background and Purpose:Previous studies have investigated the prognostic significance of skeletal muscle and adipose tissue composition and distribution in colorectal cancer patients,yet most have not differentiated between rectal and colon cancer patient cohorts.This study aimed to explore the relationship between body composition and long-term prognosis,and to develop a postoperative predictive model.Methods:Clinical data of rectal cancer patients who underwent surgical treatment at Qingdao University Affiliated Hospital from January 2018 to December 2021 were retrospectively collected.Inclusion criteria:①Age＞18 years;② Preoperative colonoscopy and pathological diagnosis of colorectal cancer;③ Complete surgical resection;④Abdominal computed tomography(CT)scan 1 month before surgery.Exclusion criteria:① Clinical data is missing;② Multiple metastases of tumors;③ Tumor T stage 0 or carcinoma in situ;④ Severe artifacts lead to poor quality CT imaging,making it difficult to distinguish between fat and muscle;⑤ Inability to obtain follow-up results.This study has been approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University(approval number:QYFYWZLL30313),and informed consent has been waived in the ethical approval process.The skeletal muscle index(SMI)and subcutaneous adipose tissue index(SATI)were calculated by dividing the areas of skeletal muscle and subcutaneous fat observed on CT scans by the square of the patient's height.Univariate and multivariate COX regression analyses were conducted to identify risk factors influencing recurrence-free survival(RFS)and overall survival(OS)in rectal cancer patients.Based on the results of the multivariate analysis,a nomogram prediction model was developed,its predictive power and accuracy were assessed using the receiver operating characteristic(ROC)curve,calibration plots and decision curve analysis(DCA),and internal validation was conducted.Results:A total of 696 patients were included in this study,with 96(13.8%)patients experiencing postoperative recurrence and 89(12.8%)patients dying.Multivariate COX regression analysis showed that SMI,SATI,tumor T stage and N stage were independent factors affecting the postoperative RFS and OS of patients.Nomogram prediction models for RFS and OS in rectal cancer patients were constructed based on the above independent predictors.The area under ROC curve(AUC)for 3-,4-and 5-year RFS was 0.862,0.846 and 0.824,respectively;the AUC for 3-,4-and 5-year OS was 0.886,0.898 and 0.875,respectively.The models were evaluated using calibration curves and decision curves,and internal validation was performed,which showed that the prediction accuracy of the models was good.Conclusion:CT body composition is an independent predictor of RFS and OS in rectal cancer patients,and the nomogram model developed based on these factors demonstrates good predictive value for patient prognosis.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Urothelial carcinoma (UC), including bladder urothelial carcinoma and upper tract urothelial carcinoma (UTUC), is the most common malignant tumor in the urinary system. Traditional cell line models fall short in simulating its tumor microenvironment and in vivo behavior. Patient-derived organoid (PDO) models offer a new way to overcome these shortcomings. This paper reviews the construction techniques of PDO models in UC, their biological simulation capabilities, and their applications in preclinical research. It also analyzes the technical limitations of these models. PDO models can retain the histological, genomic, and transcriptomic features of the parent tumor and accurately simulate the tumor microenvironment and biological behavior. They have been widely used in bladder cancer research, providing a precise platform for drug screening, personalized treatment, and immunotherapy evaluation. However, their use in UTUC research is still in its infancy. In the future, through technological optimization, PDO models are expected to enhance their value in UC research, advancing precision medicine research and clinical translation.

Objective:To investigate the clinical outcomes of nephron-sparing surgery (NSS) for tuberous sclerosis complex(TSC) -associated renal angiomyolipoma (RAML). Methods:This retrospective case-series study analyzed the clinical data of 15 TSC-RAML patients who underwent NSS at the Department of Urology, Peking Union Medical College Hospital between April 2013 and July 2024. The cohort included 4 males and 11 females. The age at TSC diagnosis was (28.5±14.5) years (range: 5 to 62 years), and the age at first surgery was (33.3±10.8) years (range: 18 to 62 years). The maximum tumor diameter( M(IQR)) was 6.4(7.9)cm (range: 3.5 to 31.5 cm). Patient baseline characteristics, surgical approach, TSC-RAML staging, imaging findings, and laboratory data were collected. Relationships between variables were analyzed using Generalized Estimating Equations with post-hoc tests. Results:A total of 18 surgical procedures were performed on the 15 patients. These included 7 open surgeries, 9 laparoscopic surgeries, and 2 laparoscopic procedures converted to open surgery. The mean preoperative serum creatinine level was (70.2±14.2) μmol/L (range: 50 to 101 μmol/L), which increased to (99.2±29.8) μmol/L (range: 47 to 171 μmol/L) on postoperative day 1. However, at one year postoperatively, serum creatinine was (76.8±13.5)μmol/L (range: 55 to 106 μmol/L),showed no significant difference from preoperative levels ( P>0.05). At the 6-month postoperative follow-up, the Utrecht Interventional Classification stage for all treated tumors had decreased to grade 1 or 2. At the 12-month follow-up (available for 13 patients), 11 patients showed no disease progression. Conclusions:NSS is a viable treatment option for rigorously selected patients with high-stage TSC-RAML. Although NSS causes transient renal function impairment, it provides effective tumor burden control. In stringently selected patients with high-stage disease and under long-term follow-up, NSS is associated with limited long-term renal impairment.

Objective:? To summarize the achievements in improving the consistency of clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing results.Methods:? From 2021 to 2024, Zhongshan Hospital Affiliated to Fudan University recruited laboratories voluntarily participating in the MSHP (Clinical LC-MS/MS Testing Consistency Program). As of Batch 202404, a total of 76 laboratories had enrolled, including 60 medical institutions (all tertiary hospitals) and 16 third-party laboratories. Test items were established, and comparative samples were distributed regularly-each item′s samples covered three concentrations (high, medium, and low). Samples were shipped via cold chain and tested within one week. Our laboratory′s measurements served as the target, with participating labs′ results within ±25% of the target deemed qualified. Passing-Bablok regression and Bland-Altman analysis were used to assess consistency.Results:Taking 3-MT (3-methoxytyramine) as an example, the coefficients of variation (CVs) for the project′s three concentration levels improved from 17.00%, 47.18%, and 4.88% in the first comparative batch to 9.59%, 9.59%, and 6.1% in Batch 202404. Passing-Bablok regression results for the 5 units participating in 3-MT testing showed that Laboratory A had proportional bias but no systematic bias (regression slope [95% CI]: 0.903 [0.862-0.952]; intercept [95% CI]: 0.912 [-1.921-6.073]). The remaining laboratories exhibited no proportional or systematic bias with the target (Laboratory B: slope 1.031 [0.961-1.147], intercept-0.733 [-4.641-8.272]; Laboratory C: slope 0.982 [0.940-1.009], intercept-0.576 [-2.675-1.891]; Laboratory D: slope 0.973 [0.939-1.066], intercept-1.168 [-6.108-1.649]; Laboratory E: slope 0.999 [0.905-1.051], intercept-1.876 [-6.111-3.508]). Bland-Altman analysis indicated that all 5 laboratories′ results generally showed good consistency with the target. Through quality feedback and optimizing sample preparation concentrations, result consistency was enhanced.? Conclusion:? Clinical LC-MS/MS testing consistency programs contribute to improving the comparability of test results.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Urothelial carcinoma (UC), including bladder urothelial carcinoma and upper tract urothelial carcinoma (UTUC), is the most common malignant tumor in the urinary system. Traditional cell line models fall short in simulating its tumor microenvironment and in vivo behavior. Patient-derived organoid (PDO) models offer a new way to overcome these shortcomings. This paper reviews the construction techniques of PDO models in UC, their biological simulation capabilities, and their applications in preclinical research. It also analyzes the technical limitations of these models. PDO models can retain the histological, genomic, and transcriptomic features of the parent tumor and accurately simulate the tumor microenvironment and biological behavior. They have been widely used in bladder cancer research, providing a precise platform for drug screening, personalized treatment, and immunotherapy evaluation. However, their use in UTUC research is still in its infancy. In the future, through technological optimization, PDO models are expected to enhance their value in UC research, advancing precision medicine research and clinical translation.