In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

BACKGROUND:Ferroptosis is a programmed cell death caused by iron dependent lipid peroxidation,involving various processes such as iron overload,lipid peroxidation,and endoplasmic reticulum stress.Research has found that ferroptosis is closely related to the occurrence and development of myocardial ischemia-reperfusion injury,and has become a new target and perspective for MIRI treatment.Traditional Chinese medicine has advantages such as multi-target,multi-level,and fewer adverse reactions,and has significant effects in the treatment of myocardial ischemia-reperfusion injury,with a far-reaching impact.OBJECTIVE:Taking ferroptosis as the starting point,to systematically elaborate and summarize the research progress in the modulation of ferroptosis against myocardial ischemia-reperfusion injury by monomers of traditional Chinese medicines such as puerarin,resveratrol,ligustrazine,and astragaloside IV in recent years.METHODS:Using the search terms"iron death,myocardial injury,myocardial ischemia-reperfusion injury,signaling pathways,traditional Chinese medicine monomers,flavonoids,polyphenols,alkaloids,terpenes,quinones"in Chinese and English from January 2013 to June 2024,literature retrieval was performed in the CNKI and PubMed respectively for literature related to ferroptosis,myocardial ischemia-reperfusion injury,and the regulatory mechanism of traditional Chinese medicine monomers.Literature that is not highly correlated,repetitive,or outdated was excluded.A total of 1 524 relevant articles were retrieved,and 76 articles were ultimately included for review.RESULTS AND CONCLUSION:Numerous animal and cell experiments have shown that ferroptosis plays an important role in the occurrence and progression of myocardial ischemia-reperfusion injury.Traditional Chinese medicine monomers such as baicalin,resveratrol,and ligustrazine can regulate iron metabolism,reduce iron deposition,and inhibit ferroptosis in myocardial cells.Pectin,quercetin,and salidroside can improve mitochondrial function,enhance cellular antioxidant capacity,and alleviate myocardial ischemia-reperfusion injury.Traditional Chinese medicine monomers can regulate ferroptosis-related signaling pathways,such as solute carrier family 7 member 11/glutathione peroxidase 4,dihydrolactate dehydrogenase/coenzyme Q10,cyclooxygenase 2/prostaglandin E2,and adenosine monophosphate-activated protein kinase,resist myocardial ischemia-reperfusion injury,and reduce ferroptosis in myocardial cells.

Objective:To assess the efficacy and safety of azacitidine combined with lenalidomide in MDS patients and explore potential mechanisms of therapeutic response.Methods:Sixteen MDS patients with TP53 mutations received azacitidine plus lenalidomide at ZhongDa Hospital, Southeast University (January 2021–June 2025). Efficacy and safety were assessed, and TP53 mutation status was correlated with treatment response. Whole-transcriptome sequencing and bioinformatics were used to explore molecular biomarkers associated with therapeutic efficacy.Results:Sixteen patients (median age 69.5 years, range 52–82; 8 males, 8 females) were enrolled. According to the Molecular International Prognostic Scoring System (IPSS-M), 1, 2, and 13 patients were classified as median low, high, and very high risk, respectively. Among 16 TP53-mutated patients, 11 had biallelic mutations and 5 had monoallelic mutations. Overall response rate was 56.3% (9/16), composite complete remission rate (CRc) was 31.3% (5/16), and hematology improvement rate was 25% (4/16). Among TP53-mutated patients, the response rate was 56.3% (9/16), with variant allele frequency dropping from 65.6% to 16.5% in responders ( P=0.017). In patients with TP53 mutations and complex karyotype, response rate was 53.8% (7/13), with 57.1% (4/7) showing disappearance of CK post-treatment. The most common grade 3–4 nonhematologic adverse events were infections (9/16, 56.3% ), including pneumonia (4/16, 25.0% ), gastrointestinal infections (3/16, 18.8% ), perianal infections (1/16, 6.3% ) and sepsis (1/16, 6.3% ). High CBX8 expression may be linked to treatment response. Conclusion:Azacitidine plus lenalidomide is an effective and safe therapy for MDS, including patients with TP53 mutations and complex karyotypes. Treatment markedly reduces TP53 variant allele frequency in responders, and high CBX8 expression may predict therapeutic response.

BACKGROUND:Ferroptosis is a programmed cell death caused by iron dependent lipid peroxidation,involving various processes such as iron overload,lipid peroxidation,and endoplasmic reticulum stress.Research has found that ferroptosis is closely related to the occurrence and development of myocardial ischemia-reperfusion injury,and has become a new target and perspective for MIRI treatment.Traditional Chinese medicine has advantages such as multi-target,multi-level,and fewer adverse reactions,and has significant effects in the treatment of myocardial ischemia-reperfusion injury,with a far-reaching impact.OBJECTIVE:Taking ferroptosis as the starting point,to systematically elaborate and summarize the research progress in the modulation of ferroptosis against myocardial ischemia-reperfusion injury by monomers of traditional Chinese medicines such as puerarin,resveratrol,ligustrazine,and astragaloside IV in recent years.METHODS:Using the search terms"iron death,myocardial injury,myocardial ischemia-reperfusion injury,signaling pathways,traditional Chinese medicine monomers,flavonoids,polyphenols,alkaloids,terpenes,quinones"in Chinese and English from January 2013 to June 2024,literature retrieval was performed in the CNKI and PubMed respectively for literature related to ferroptosis,myocardial ischemia-reperfusion injury,and the regulatory mechanism of traditional Chinese medicine monomers.Literature that is not highly correlated,repetitive,or outdated was excluded.A total of 1 524 relevant articles were retrieved,and 76 articles were ultimately included for review.RESULTS AND CONCLUSION:Numerous animal and cell experiments have shown that ferroptosis plays an important role in the occurrence and progression of myocardial ischemia-reperfusion injury.Traditional Chinese medicine monomers such as baicalin,resveratrol,and ligustrazine can regulate iron metabolism,reduce iron deposition,and inhibit ferroptosis in myocardial cells.Pectin,quercetin,and salidroside can improve mitochondrial function,enhance cellular antioxidant capacity,and alleviate myocardial ischemia-reperfusion injury.Traditional Chinese medicine monomers can regulate ferroptosis-related signaling pathways,such as solute carrier family 7 member 11/glutathione peroxidase 4,dihydrolactate dehydrogenase/coenzyme Q10,cyclooxygenase 2/prostaglandin E2,and adenosine monophosphate-activated protein kinase,resist myocardial ischemia-reperfusion injury,and reduce ferroptosis in myocardial cells.

Objective:To assess the efficacy and safety of azacitidine combined with lenalidomide in MDS patients and explore potential mechanisms of therapeutic response.Methods:Sixteen MDS patients with TP53 mutations received azacitidine plus lenalidomide at ZhongDa Hospital, Southeast University (January 2021–June 2025). Efficacy and safety were assessed, and TP53 mutation status was correlated with treatment response. Whole-transcriptome sequencing and bioinformatics were used to explore molecular biomarkers associated with therapeutic efficacy.Results:Sixteen patients (median age 69.5 years, range 52–82; 8 males, 8 females) were enrolled. According to the Molecular International Prognostic Scoring System (IPSS-M), 1, 2, and 13 patients were classified as median low, high, and very high risk, respectively. Among 16 TP53-mutated patients, 11 had biallelic mutations and 5 had monoallelic mutations. Overall response rate was 56.3% (9/16), composite complete remission rate (CRc) was 31.3% (5/16), and hematology improvement rate was 25% (4/16). Among TP53-mutated patients, the response rate was 56.3% (9/16), with variant allele frequency dropping from 65.6% to 16.5% in responders ( P=0.017). In patients with TP53 mutations and complex karyotype, response rate was 53.8% (7/13), with 57.1% (4/7) showing disappearance of CK post-treatment. The most common grade 3–4 nonhematologic adverse events were infections (9/16, 56.3% ), including pneumonia (4/16, 25.0% ), gastrointestinal infections (3/16, 18.8% ), perianal infections (1/16, 6.3% ) and sepsis (1/16, 6.3% ). High CBX8 expression may be linked to treatment response. Conclusion:Azacitidine plus lenalidomide is an effective and safe therapy for MDS, including patients with TP53 mutations and complex karyotypes. Treatment markedly reduces TP53 variant allele frequency in responders, and high CBX8 expression may predict therapeutic response.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Viral myocarditis(VMC),as the most common type of myocarditis,can progress to chronic myocarditis and even heart failure,ultimately leading to death.Nuclear factor κB(NF-κB)is a multifunctional transcription factor involved in regulating a wide range of biological processes.Existing evidence suggests that the balance between pro-inflammatory and anti-inflammatory factors plays a decisive role in the prognosis of VMC.The NF-κB pathway mediates inflammatory responses and regulates pathways such as cell apoptosis,energy metabolism,oxidative stress,and insulin resistance to participate in the pathological progression of VMC.This article analyzes and summarizes the molecular mechanism of NF-κB signaling pathway regulation in VMC from the above five aspects,to provide a reference for future basic research and for the clinical diagnosis and treatment of VMC.

Viral myocarditis(VMC),as the most common type of myocarditis,can progress to chronic myocarditis and even heart failure,ultimately leading to death.Nuclear factor κB(NF-κB)is a multifunctional transcription factor involved in regulating a wide range of biological processes.Existing evidence suggests that the balance between pro-inflammatory and anti-inflammatory factors plays a decisive role in the prognosis of VMC.The NF-κB pathway mediates inflammatory responses and regulates pathways such as cell apoptosis,energy metabolism,oxidative stress,and insulin resistance to participate in the pathological progression of VMC.This article analyzes and summarizes the molecular mechanism of NF-κB signaling pathway regulation in VMC from the above five aspects,to provide a reference for future basic research and for the clinical diagnosis and treatment of VMC.

Objective:To investigate the status of glucolipid metabolism and insulin resistance in patients with first-episode non-medicated schizophrenia, and to explore their relationship with psychiatric symptoms and cognitive function.Methods:One hundred and seventeen patients with first-episode non-medicated schizophrenia admitted to Wenzhou Seventh People′s Hospital from January 2018 to August 2020 were included in case group, and 61 healthy subjects with physical examination during the same period were used as control group. The glucose metabolism, including serum fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG), fasting insulin (FINS), fasting C peptide; lipid metabolism, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C); apolipoprotein A1 (Apo-A1) and homeostatic model assessment insulin resistance index (HOMA-IR) level were compared between 2 groups. The abnormal glucolipid metabolism and incidence rate of insulin resistance were counted in the two groups. According to the condition of abnormal glucolipid metabolism or insulin resistance in case group, the patients were divided into abnormal glucolipid metabolism group and non-abnormal group, and insulin resistance group and non-insulin resistance group. The psychiatric symptoms (positive and negative symptom scale, PANSS) and cognitive function (MATRICS consensus cognitive battery, MCCB) were compared between 2 groups. Pearson correlation analysis was used to explore the correlation between glucolipid metabolism and insulin resistance and psychiatric symptoms and cognitive function in case group.Results:The levels of glucolipid metabolism indexes of 2 h PBG, FINS, fasting C peptide, TG and HOMA-IR in case group were significantly higher than those in control group: (7.06 ± 1.88) mmol/L vs. (6.19 ± 1.53) mmol/L, (8.61 ± 2.46) mU/L vs. (6.25 ± 1.71) mU/L, (0.49 ± 0.16) nmol/L vs. (0.32 ± 0.09) nmol/L, (1.33 ± 0.47) mmol/L vs. (1.02 ± 0.24) mmol/L, 2.01 ± 0.71 vs. 1.51 ± 0.45 ( P<0.05); while the levels of HDL-C and Apo-A1 were significantly lower than those in control group: (1.19 ± 0.38) mmol/L vs. (1.57 ± 0.32) mmol/L, (1.21 ± 0.25) g/L vs. (1.43 ± 0.17) g/L ( P<0.05). The total incidence rate of abnormal glucolipid metabolism or insulin resistance in case group was significantly higher than that in control group: 62.39%(73/117) vs. 13.11%(8/61) ( P<0.05). The scores of dimensions of positive symptoms, negative symptoms and general psychopathology and total score of PANSS in combined group were significantly higher than those in non-abnormal group: (25.14 ± 5.09) scores vs. (22.95 ± 4.72) scores, (24.68 ± 5.25) scores vs. (22.05 ± 4.59) scores, (41.52 ± 5.85) scores vs. (38.12 ± 4.18) scores, (94.68 ± 11.64) scores vs. (85.43 ± 8.51) scores ( P<0.05). The above scores points in insulin resistance group were higher than points in non-insulin resistance group: (26.62 ± 4.18) scores vs. (23.62 ± 4.98) scores, (25.92 ± 5.07) scores vs. (23.02 ± 4.96) scores, (42.94 ± 5.26) scores vs. (39.43 ± 4.47) scores, (97.35 ± 10.07) scores vs. (89.37 ± 10.25) scores ( P<0.05). The scores of continuous performance test-identical pairs (CPT-IP), working memory (WM), brief visuospatial memory test-revised (BVMT-R) and Mayer-Salovey-Caruso emotional intelligence test (MSCEIT) of MCCB scale in abnormal glucolipid metabolism group were significantly lower than those in non-abnormal group: (23.82 ± 5.21) scores vs. (27.15 ± 4.69) scores, (21.72 ± 5.95) scores vs. (25.35 ± 5.14) scores, (19.56 ± 5.28) scores vs. (22.34 ± 5.43) scores, (22.62 ± 5.13) scores vs. (26.47 ± 4.96) scores ( P<0.05), and the scores in insulin resistance group were significantly lower: (22.26 ± 4.84) scores vs. (25.42 ± 5.12) scores, (20.35 ± 4.87) scores vs. (23.46 ± 5.08) scores, (18.05 ± 4.27) scores vs. (20.98 ± 5.71) scores, (21.15 ± 4.67) scores vs. (24.48 ± 5.02) scores ( P<0.05). Pearson correlation analysis showed that 2 h PBG in case group was positively correlated with PANSS positive symptoms ( P<0.05), and was negatively correlated with CPT-IP and MSCEIT in MCCB scale ( P<0.05). FINS and HOMA-IR were positively correlated with positive symptoms, negative symptoms and PANSS total score ( P<0.05), and were negatively correlated with CPT-IP, WM, BVMT-R and MSCEIT ( P<0.05). HDL-C was negatively correlated with positive symptoms ( P<0.05), and was positively correlated with CPT-IP, WM and MSCEIT ( P<0.05). Apo-A1 was negatively correlated with positive symptoms and negative symptoms ( P<0.05), and was positively correlated with CPT-IP and WM ( P<0.05). Conclusions:Abnormal glucolipid metabolism and insulin resistance have a higher detection rate in first-episode non-medicated schizophrenia, and have a certain relationship with the psychiatric symptoms and cognitive impairment of patients.

OBJECTIVETo raise the awareness of adenosquamous carcinoma of pancreas and discuss the treatment of it.

METHODSClinical data of 80 cases of pancreas adenosquamous carcinoma patients in the Department of Pancreas Surgery of Changhai Hospital of Second Military Medical University from December 2003 to October 2011 were analyzed. The diagnose and treatment methods were discussed. There were 61 male cases and 19 female cases who aged from 28 to 81 years, with an average age of 60 years. The primary symptoms included 46 cases (57.5%) of abdominal malaise, 6 cases (7.5%) of low back pain, 4 cases (5.0%) of abdominal swelling pain with low back pain, 15 cases (18.8%) of abdominal swelling pain with jaundice, 5 cases (6.3%) of painless jaundice, 3 cases (3.8%) of significantly decreased body-weight and 1 case (1.3%) of no symptom. All the patients had been identified as pancreas tumor suffers by ultrasound, enhanced CT scan or MRI. Totally there were 43 cases of head/unciform process tumors, 15 cases of pancreas body tumors and 22 pancreas tail cases.Health situation of all cases were follow-up observed in the outpatient department or telephoned every 3 months till 24 months after the surgery.

RESULTSAmong the 80 patients, 19 patients underwent pancreaticoduodenectomy (PD) , 19 patients received pylorus-preserving PD, with 4 cases of palliative resection and 1 case of total pancreatectomy. The volume of bleeding during the surgery varied from 50 to 3 500 ml with a blood transfusion volume varied from 0 to 4 000 ml. Consumed time for PD procedures was 90 to 260 min with 60 to 150 min for body and (or) tail resection with or without lienectomy. The mean diameter of tumor was (4.9 ± 2.2) cm. Pathological tests showed 35 cases of positive lymph nodes, adjacent organ invasion happened in 35 patients, however, nerve invasion were found in 68 cases.Eighteen cases occurred postoperative complications, including bleeding, pancreatic fistula, gastric emptying, incision fat liquefaction and infection, pleural effusion, ascites and nervous diarrhea. There were only 48 effective follow-up patients, with a loss ratio of follow-up by 40.0%, reasons for the loss includes change of contact information, refuse or unable to provide useful information by the relatives of the patients.Sixteen patients received chemotherapy, and 8 patients received radiotherapy after operation. All patients were dead in the effective follow-ups. The postoperative median survival time was 6 months (0.1 to 23.0 months).

CONCLUSIONSAdenosquamous carcinoma of pancreas is a rare kind of malignant tumor, nerve invasion can be found in almost all the cases. Patients with adenosquamous carcinoma of pancreas have an unfavorable prognosis. The principle treatments are surgery, radiotherapy and chemotherapy.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Adenosquamous ; mortality ; pathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Pancreas ; pathology ; Pancreatectomy ; methods ; Pancreatic Neoplasms ; mortality ; pathology ; surgery ; Pancreaticoduodenectomy ; methods ; Postoperative Complications ; mortality ; Prognosis ; Young Adult