Objective:This study investigated the underlying causes of discordance between multiplex fluorescence polymerase chain reaction (PCR)-capillary electrophoresis in determining MSI and immunohistochemistry (IHC) for mismatch repair (MMR) protein evaluation in gastrointestinal adenocarcinomas, aiming to improve interpretation accuracy and guide clinical precision treatment strategies.Methods:A retrospective analysis was conducted on 511 surgically resected or biopsied specimens (161 gastric adenocarcinomas and 350 colorectal adenocarcinomas) diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January to June 2024. MMR protein expression of tumors was evaluated by IHC, while MSI status was assessed using the 2B3D National Cancer Institute (NCI) Panel through multiplex fluorescence PCR-capillary electrophoresis on tumor DNA and matched normal DNA. The concordance between the two methods was analyzed, and factors contributing to the discordance were investigated. Cases with unstable dinucleotide loci only in the 2B3D NCI Panel, focal MMR protein loss, or unexplained discrepancies underwent validation using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis markers or next-generation sequencing (NGS).Results:In the 511 gastrointestinal adenocarcinomas, the results of the two methods were discordant in 15 cases (2.9%), with a significantly higher discordantrate in gastric cancers (7.5%, 12/161) compared to colorectal cancers (0.9%, 3/350; P＜0.001). Key contributors to the discordance included: sampling limitations (6 cases), 2B3D NCI Panel design constraints (3 cases),tumor heterogeneity (3 cases),isolated MSH6 deficiency (1 case),and unexplained discrepancies (2 cases).Validation studies demonstrated that cases with dinucleotide-only instability showed concordance with IHC after using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis and NGS verifications. Specimens with focal MMR protein loss and unexplained discrepancies aligned with initial PCR results upon NGS validation. Unexplained cases harbored Kirsten rat sarcoma class Ⅰ variants and multiple class Ⅱ genetic alterations. Conclusions:Colorectal adenocarcinoma demonstrated higher concordance between PCR-capillary electrophoresis and IHC than gastric adenocarcinoma.Discordant results require systematic evaluation including technical review, specimen quality control, and supplemental NGS analysis to resolve discrepancies.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Purpose To investigate the clinical features of gastrointestinal leiomyomas(GLs)with scattered ex-pression of CD117 and DOG1,and to evaluate their biological behavior as well as their different diagnositic value from gastrointestinal stromal tumors(GISTs).Methods Clinical data from 17 cases of surgically resected GLs were col-lected.Immunohistochemistry using the EnVision method was performed to detect SMA,desmin,h-caldesmon,DOG1,CD117,and CD34.First-generation sequencing was performed to analyze exons 9-20 of the KIT gene and ex-ons 12 and 18 of the PDGFRA gene.Results Tumors occured in the stomach(8 cases)and esophagus(9 cases).Clinical manifestations included dull upper abdominal pain,dysphagia,chest pain,and fever.During a follow-up peri-od of 58-88 months,no recurrence was observed,and all patients had a favorable prognosis.Histologically,tumor cells were spindle-shaped and arranged in bundles or a woven pattern.Interstitial cells of Cajal appeared spindle-shaped or stellate with indistinct borders and dispersed chromatin.Tumor cells showed diffuse positivity for SMA,desmin,and h-caldesmon(100％).Interstitial cells of Cajal exhibited focal positive for CD117 and DOG1,with an o-verall positive rate of 9％for each marker.No pathogenic mutations of the KIT or PDGFRA genes were detected by first-generation sequencing.Conclusion Although some GLs contained interstitial cells of Cajal that showed focal pos-itivity for CD117 and DOG1,sequencing and long-term follow-up confirmed that their biological behavior differed from that of GISTs,with no malignant potential.Surgical resection remained the mainstay of treatment,and the prognosis was favorable.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Purpose To investigate the clinical features of gastrointestinal leiomyomas(GLs)with scattered ex-pression of CD117 and DOG1,and to evaluate their biological behavior as well as their different diagnositic value from gastrointestinal stromal tumors(GISTs).Methods Clinical data from 17 cases of surgically resected GLs were col-lected.Immunohistochemistry using the EnVision method was performed to detect SMA,desmin,h-caldesmon,DOG1,CD117,and CD34.First-generation sequencing was performed to analyze exons 9-20 of the KIT gene and ex-ons 12 and 18 of the PDGFRA gene.Results Tumors occured in the stomach(8 cases)and esophagus(9 cases).Clinical manifestations included dull upper abdominal pain,dysphagia,chest pain,and fever.During a follow-up peri-od of 58-88 months,no recurrence was observed,and all patients had a favorable prognosis.Histologically,tumor cells were spindle-shaped and arranged in bundles or a woven pattern.Interstitial cells of Cajal appeared spindle-shaped or stellate with indistinct borders and dispersed chromatin.Tumor cells showed diffuse positivity for SMA,desmin,and h-caldesmon(100％).Interstitial cells of Cajal exhibited focal positive for CD117 and DOG1,with an o-verall positive rate of 9％for each marker.No pathogenic mutations of the KIT or PDGFRA genes were detected by first-generation sequencing.Conclusion Although some GLs contained interstitial cells of Cajal that showed focal pos-itivity for CD117 and DOG1,sequencing and long-term follow-up confirmed that their biological behavior differed from that of GISTs,with no malignant potential.Surgical resection remained the mainstay of treatment,and the prognosis was favorable.

Objective:This study investigated the underlying causes of discordance between multiplex fluorescence polymerase chain reaction (PCR)-capillary electrophoresis in determining MSI and immunohistochemistry (IHC) for mismatch repair (MMR) protein evaluation in gastrointestinal adenocarcinomas, aiming to improve interpretation accuracy and guide clinical precision treatment strategies.Methods:A retrospective analysis was conducted on 511 surgically resected or biopsied specimens (161 gastric adenocarcinomas and 350 colorectal adenocarcinomas) diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January to June 2024. MMR protein expression of tumors was evaluated by IHC, while MSI status was assessed using the 2B3D National Cancer Institute (NCI) Panel through multiplex fluorescence PCR-capillary electrophoresis on tumor DNA and matched normal DNA. The concordance between the two methods was analyzed, and factors contributing to the discordance were investigated. Cases with unstable dinucleotide loci only in the 2B3D NCI Panel, focal MMR protein loss, or unexplained discrepancies underwent validation using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis markers or next-generation sequencing (NGS).Results:In the 511 gastrointestinal adenocarcinomas, the results of the two methods were discordant in 15 cases (2.9%), with a significantly higher discordantrate in gastric cancers (7.5%, 12/161) compared to colorectal cancers (0.9%, 3/350; P＜0.001). Key contributors to the discordance included: sampling limitations (6 cases), 2B3D NCI Panel design constraints (3 cases),tumor heterogeneity (3 cases),isolated MSH6 deficiency (1 case),and unexplained discrepancies (2 cases).Validation studies demonstrated that cases with dinucleotide-only instability showed concordance with IHC after using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis and NGS verifications. Specimens with focal MMR protein loss and unexplained discrepancies aligned with initial PCR results upon NGS validation. Unexplained cases harbored Kirsten rat sarcoma class Ⅰ variants and multiple class Ⅱ genetic alterations. Conclusions:Colorectal adenocarcinoma demonstrated higher concordance between PCR-capillary electrophoresis and IHC than gastric adenocarcinoma.Discordant results require systematic evaluation including technical review, specimen quality control, and supplemental NGS analysis to resolve discrepancies.

Objective: To evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia (ALL) enrolled in Shanghai Children's Medical Center-Acute Lymphoblastic Leukemia-2005(SCMC-ALL-2005) multicenter study. Methods: Between May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease (MRD). Kaplan-Meier method was used to generate overall survival (OS) and event-free survival(EFS) curves. Cox proportional hazards models were used for multivariate analyses. Results: The patients were followed up to December 31, 2016, the median follow-up time was 69 months (24-141 months). The 5-year and 10-year OS rates were (80.0±1.0)% and (76.0±2.0)%. The 5-year and 10-year EFS rates were (69.0±1.0)% and (66.0±2.0)%. The 5-year and 10-year relapse rates were (23.0±1.0)% and (25.0±2.0)%. The 5-year OS and EFS for low risk (LR), intermediate risk (IR) and high risk (HR) were (91.1±1.4)% and (83.3±1.8)%, (79.2±1.5)% and (68.9±1.7)%, (52.9±4.4)% and (30.0±3.8)%, respectively. MRD negative status (<0.01%) on day 55 was seen in 792 patients (82.8%) and positive MRD on day 55 was associated with poor prognosis (OR=1.9, 95%CI: 1.3-2.7, P=0.001). Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17(70.8%) of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%. Conclusions In this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.

Carcinoma, Hepatocellular ; diagnosis ; surgery ; therapy ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; surgery ; therapy

BACKGROUND: Conventional means in treatment of distal tibiofibular syndesmosis disruption include plaster cast or splint immobilization as external fixation and internal fixation using screws, and bone bolts or plates;however, some disadvantages such as unstable fixation and uncertain fixation exist.OBJECTIVE: To observe the primary clinical curative effect of newly self-developed fixation, Hook-plate fixation (HPF), for distal tibiofibular syndesmosis disruption and its biochemical characteristics of HPF.DESIGN: Self-control observation.PARTICIPANTS: We recruited 23 patients with sustaining abruption of lower tibiofibular ligament union with fibular fracture who received treatment in the Department of Orthopedics, Affiliated Hospital of Yangzhou University Medical College, between October 2001 and March 2004. According to the Lauge-Hansen classification system, there were 11 cases of supination-lateral rotations, 7 cases of pronation-lateral rotations and 5cases of pronation-abductions. Among them 14 had bimalleolar fractures and 9 had trimalleolar fractures.METHODS: HPF was used on the 23 patients with distal tibiofibular syndesmosis disruption. Radiographs were taken routinely. Talocrural joint function exercise was recommended at week 1 and partial weight bearing was allowed 2 months later. Functions were evaluated according to modified Mazur's criteria (excellent, good, fair and poor).MAIN OUTCOME MEASURES: ①Healing time and function ev aluation after operation for distal tibiofibular syndesmosis disruption. ② Adverse events and side effectsRESULTS: Totally 23 patients entered the result analysis, with the mean of 11 months' follow-up. ①Results of healing time and function evaluation in the patients after operation for distal tibiofibular syndesmosis disruption: The healing time of fracture ranged from 12 to 18 weeks: 16 cases were excellent, 5 good, and 2 fair. ② Adverse events and side effects:There was no separation of the tibiofibular space, the distance between medial malleolus or lateral malleolus and anklebone was symmetrical.There was no mobilization or rupture of the internal fixation after operation.CONCLUSION: HPF is applied in treating distal tibiofibular syndesmosis disruption. It causes no postoperative complications, and can recover the ankle joint function with stable internal fixation and good biomechanical features.