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.

Objective To systematically review the incidence of antibiotic-associated diarrhea(AAD)in critically ill patients in China,and to provide evidence-based basis for the rational use of antibiotics.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data,VIP and SionMed databases were electronically searched to collect studies on the incidence of AAD in acute and critically ill patients in China from inception to April 23,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed using Stata 17.0 software.Results A total of 50 studies involving 26,512 subjects were included.Meta-analysis results showed that the incidence of AAD in critically ill patients in China was 26.5%[95%CI(22.9%,30.1%)].Subgroup analysis showed that the incidence of AAD in critically ill children in China was 40.6%[95%CI(30.7%,50.4%)],and in critically ill adults in China was 18.7%[95%CI(16.1%,21.4%)],among which the incidence of AAD in children in East China and adults in Southwest China was the lowest.The incidence of AAD in children and adults in Northeast China was the highest.Conclusion The incidence of AAD in critically ill patients in China is relatively high,and it is necessary to carry out effective intervention measures,such as rational selection and standardized use of antibiotics,early prevention and detection of AAD occurrence,to reduce the medical burden caused by AAD in critically ill patients and improve the quality of prognosis.

Objective To analyze the epidemiological characteristics and spatiotemporal clustering of varicella in Lu'an City from 2005 to 2023, and to provide a scientific basis for optimizing varicella prevention and control strategies. Methods Data on varicella cases were collected through the Chinese Center for Disease Control and Prevention Information System. Descriptive epidemiology, temporal trend analysis, seasonal analysis, spatiotemporal clustering analysis, and spatial autocorrelation analysis were conducted using QGIS, JoinPoint, SaTScan and GeoDa software. Results The average annual reported incidence rate of varicella in Lu'an City from 2005 to 2023 was 34.55/100,000, showing a trend of initial increase followed by a decrease. The peak incidence occurred from October to January of the following year (RR=1.97, LLR=1743.95, P=0.001). Students aged 0 to 19 was the primary affected group. Spatiotemporal scan analysis revealed four types of spatiotemporal clusters, with the cluster in Jin'an District from October 2017 to December 2023 being particularly prominent (RR=2.87，LLR=1734.15，P<0.001). Spatial autocorrelation analysis indicated significant clustering of varicella cases in the main urban area (Moran's I=0.216，Z=4.786，P=0.003). Conclusion The incidence of varicella in Lu'an City exhibits distinct seasonal and spatial clustering, and schools and kindergartens in the main urban area are the key to varicella prevention and control. It is necessary to enhance the monitoring of disease outbreaks during peak periods and in key areas, and to increase the two-dose vaccination rate for varicella in areas with case aggregation and among key populations.

Objective: To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.

Objective To systematically review the incidence of antibiotic-associated diarrhea(AAD)in critically ill patients in China,and to provide evidence-based basis for the rational use of antibiotics.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data,VIP and SionMed databases were electronically searched to collect studies on the incidence of AAD in acute and critically ill patients in China from inception to April 23,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed using Stata 17.0 software.Results A total of 50 studies involving 26,512 subjects were included.Meta-analysis results showed that the incidence of AAD in critically ill patients in China was 26.5%[95%CI(22.9%,30.1%)].Subgroup analysis showed that the incidence of AAD in critically ill children in China was 40.6%[95%CI(30.7%,50.4%)],and in critically ill adults in China was 18.7%[95%CI(16.1%,21.4%)],among which the incidence of AAD in children in East China and adults in Southwest China was the lowest.The incidence of AAD in children and adults in Northeast China was the highest.Conclusion The incidence of AAD in critically ill patients in China is relatively high,and it is necessary to carry out effective intervention measures,such as rational selection and standardized use of antibiotics,early prevention and detection of AAD occurrence,to reduce the medical burden caused by AAD in critically ill patients and improve the quality of prognosis.

Objective:To explore the occurrence and clinical characteristics of infusion-related reactions (IRRs) caused by lecanemab in Chinese patients with Alzheimer disease, and summarize the nursing management experience of IRRs.Methods:This study was a single center retrospective study and the subjects were Alzheimer′s disease patients who received lecanemab (10 mg/kg, once every 2 weeks) in the Department of Neurology, Xuanwu Hospital, Capital Medical University from June 26 to August 18, 2024. The occurrence, clinical characteristics, severity, and outcome of IRRs that occurred during the treatment of lecanemab in these patients were descriptively analyzed.Results:A total of 45 patients were included in the study, including 15 males (33.3%) and 30 females (66.7%); the age ranged from 52 to 82 years, with a median age of 62 years. Among the 45 patients, 15 (33.3%) developed IRRs, including 6 males and 9 females, and 2 of them had a previous history of allergy. In the 15 patients, there were 3, 8, 1 and 3 patients with 1, 2, 3 and 4 treatment cycles, respectively; 13 patients were pretreated with diphenhyd-ramine 30 minutes before lecanemab treatment; 14 patients had IRRs in the first cycle of lecanemab treatment, and 1 in the second cycle; IRRs occurred within 5 hours after finishing the intravenous infusion of lecanemab in 13 patients and on the second day after the administration in 2 patients. The main manifestations of IRRs were fever and chills; some patients had headache, nausea, and vomiting symptoms, and only 1 patient developed rash and itching. After symptomatic treatments, these symptoms in the 13 patients were relieved soon, and IRRs did not recur after the continued treatment of lecanemab according to the regime. The severity of IRRs was grade 1, 2, and 3 in 5, 9, and 1 patient, respectively. The incidence of severe IRRs was 2.2% (1/45).Conclusions:IRRs are common adverse reactions of lecanemab, mainly characterized by fever and chills, with mild severity. Generally, lecanemab-related IRRs occurs after the first administration, and may not occur again in the continued treatments. Vital signs should be routinely monitored in lecanemab treatment. Once IRRs occur, timely treatments should be given according to the severity, and the prognosis is usually good.

Objective:To explore the occurrence and clinical characteristics of infusion-related reactions (IRRs) caused by lecanemab in Chinese patients with Alzheimer disease, and summarize the nursing management experience of IRRs.Methods:This study was a single center retrospective study and the subjects were Alzheimer′s disease patients who received lecanemab (10 mg/kg, once every 2 weeks) in the Department of Neurology, Xuanwu Hospital, Capital Medical University from June 26 to August 18, 2024. The occurrence, clinical characteristics, severity, and outcome of IRRs that occurred during the treatment of lecanemab in these patients were descriptively analyzed.Results:A total of 45 patients were included in the study, including 15 males (33.3%) and 30 females (66.7%); the age ranged from 52 to 82 years, with a median age of 62 years. Among the 45 patients, 15 (33.3%) developed IRRs, including 6 males and 9 females, and 2 of them had a previous history of allergy. In the 15 patients, there were 3, 8, 1 and 3 patients with 1, 2, 3 and 4 treatment cycles, respectively; 13 patients were pretreated with diphenhyd-ramine 30 minutes before lecanemab treatment; 14 patients had IRRs in the first cycle of lecanemab treatment, and 1 in the second cycle; IRRs occurred within 5 hours after finishing the intravenous infusion of lecanemab in 13 patients and on the second day after the administration in 2 patients. The main manifestations of IRRs were fever and chills; some patients had headache, nausea, and vomiting symptoms, and only 1 patient developed rash and itching. After symptomatic treatments, these symptoms in the 13 patients were relieved soon, and IRRs did not recur after the continued treatment of lecanemab according to the regime. The severity of IRRs was grade 1, 2, and 3 in 5, 9, and 1 patient, respectively. The incidence of severe IRRs was 2.2% (1/45).Conclusions:IRRs are common adverse reactions of lecanemab, mainly characterized by fever and chills, with mild severity. Generally, lecanemab-related IRRs occurs after the first administration, and may not occur again in the continued treatments. Vital signs should be routinely monitored in lecanemab treatment. Once IRRs occur, timely treatments should be given according to the severity, and the prognosis is usually good.

Objective:To investigate whether the necroptosis pathway receptor interacting protein 1-receptor interacting protein 3-mixed lineage kinase domain-like protein (RIP1-RIP3-MLKL) is involved in fluoride-induced osteoblastic death.Methods:Human osteosarcoma cell line (Saos-2 cells) were cultured in vitro and divided into NC group, sodium fluoride (NaF) groups (5.0, 10.0, 20.0 and 40.0 mg/L NaF), necroptosis inhibitor Necrostatin-1 (Nec-1) group (50.0 μmol/L Nec-1) and NaF + Nec-1 groups (5.0, 10.0, 20.0 and 40.0 mg/L NaF + 50.0 μmol/L Nec-1). After cultured for 24 and 48 h, respectively, cell proliferation was determined via the CCK-8 method, and the activity of lactate dehydrogenase (LDH) was determined by chemical colorimetry. To further analyze the influence of NaF on RIP1-RIP3-MLKL pathway, Saos-2 cells were divided into NCⅡgroup and NaFⅡgroups (2.5, 5.0, 10.0, 20.0 and 40.0 mg/L NaF). After cultured for 24 and 48 h, respectively, the protein expression levels of RIP1, RIP3 and MLKL were determined by Western blotting. Results:The cell proliferation rates (%: 100.00 ± 0.59, 104.90 ± 0.44, 104.16 ± 0.41, 82.45 ± 1.91, 64.59 ± 1.83, 103.56 ± 0.41, 107.18 ± 0.87, 105.35 ± 1.28, 89.63 ± 1.20, 77.51 ± 1.30; 100.00 ± 0.33, 107.92 ± 0.44, 101.78 ± 1.06, 75.45 ± 0.39, 57.94 ± 1.17, 106.74 ± 0.21, 111.85 ± 0.21, 107.82 ± 0.68, 82.34 ± 0.56, 70.19 ± 0.99) among all groups were significantly different at both 24 and 48 h ( F = 77.13, 2 313.43, P < 0.05). Except the cell proliferation rate of the 10.0 mg/L NaF + Nec-1 group that was not significantly different with that of the 10.0 mg/L NaF group at 24 h ( P > 0.05), the cell proliferation rates of other NaF + Nec-1 groups were significantly higher than those of corresponding NaF groups at both 24 and 48 h ( P < 0.05). The proliferation rate was negatively correlated with fluoride concentration ( r24 h = - 0.976, r48 h = - 0.969, P < 0.001). The LDH activity in all concentrations of NaF groups was significantly higher than that in NC group and corresponding NaF + Nec-1 groups at both 24 and 48 h ( P < 0.05). The LDH activity was positively correlated with fluoride concentration ( r24 h = 0.985, r48 h = 0.988, P < 0.001). The protein expression levels of RIP1, RIP3 and MLKL of 5.0 mg/L NaFⅡ group at 24 h, RIP3 of 5.0 mg/L NaFⅡ group at 48 h, and RIP1, RIP3 and MLKL of 10.0, 20.0 and 40.0 mg/L NaFⅡ groups at both 24 and 48 h were higher than that in NCⅡ group ( P < 0.05). The protein expression levels of RIP1, RIP3 and MLKL were positively correlated with fluoride concentration ( r24 h-RIP1 = 0.881, r48 h-RIP1 = 0.952, r24 h-RIP3 = 0.867, r48 h-RIP3 = 0.938, r24 h-MLKL = 0.758, r48 h-MLKL = 0.907, P < 0.001). Conclusion:Fluoride can directly cause necroptosis of osteoblasts through the RIP1-RIP3-MLKL pathway, and the severity of cell damage is closely related to fluoride concentration, Nec-1 has partially reversed the effects of fluoride.

Objective:To investigate the clinic value of ultrasound 3-dimensional shear wave elastography (3D-SWE) in therapeutic effect evaluation of neoadjuvant chemotherapy (NAC) for HER-2 positive breast cancer patients.Methods:A total of 43 lesions from 43 HER-2 positive breast cancer patients were selected and all of the lesions were confirmed by biopsy. Ultrasound examination was performed routinely before each chemotherapy cycle. The interested regions were selected under the 3-dimensional (3D) elasticity and gray-scale mode, the relevant data such as shear waves in the transverse, longitudinal and coronal sections of the mass were generated automatically. According to the histopathological results, the patients were divided into the pathological complete remission (pCR) group and the incomplete remission (non-pCR) group. The maximum elastic hardness value (Emax) and the reduction degree (ΔEmax) of the lesions in the two groups were measured and compared in each cycle of NAC. The accuracy of 3D-SWE technique for predicting the efficacy of NAC was evaluated using indicators such as sensitivity, specificity and area under the receiver operating characteristic (ROC) curve.Results:The clinicopathologic features between pCR group (18 cases) and non-pCR Group (25 cases) were not significantly different ( P>0.05). Compared with pre-chemotherapy, the Emax values of pCR group and non-pCR Group during chemotherapy were declined ( P<0.05). Moreover, the Emax values of pCR group before and after chemotherapy were lower than those of non-pCR group ( P<0.05). At the end of the first cycle of chemotherapy, the predictive specificity, sensitivity and area under the curve (AUC) of pCR group were 72.0%, 83.3% and 0.838 (95% CI=0.680~0.930) respectively when the cutoff value of Emax was 118 kPa. At the end of the second cycle, the predictive specificity, sensitivity and AUC of pCR group were 76.0%, 83.3% and 0.863 (95% CI=0.720~0.940) respectively when the cutoff value of Emax was 87 kPa. At the end of the third cycle, the predictive specificity and sensitivity and the AUC of the pCR group were 88.0%, 77.8% and 0.893 (95% CI=0.760~0.970) when the cutoff value of Emax was 57 kPa. At the end of the fourth cycle of chemotherapy, the predictive specificity, sensitivity and AUC of pCR group were 92.5%, 88.9% and 0.960 (95% CI=0.850~0.990) respectively when the cutoff value of Emax was 30 kPa. After one cycle of NAC, the predictive sensitivity and specificity and AUC of pCR group were 88.0%, 60.0%, and 0.719 (95% CI=0.620~0.890) when the cutoff value of ΔEmax was 16.8%. After two cycles, the predictive sensitivity, specificity and AUC of pCR group were 55.5%, 80.0% and 0.712 (95% CI=0.550~0.840) when the cutoff value of ΔEmax was 34.9%. After three cycles, the predictive sensitivity, specificity and AUC of pCR group were 67.4%, 81.2% and 0.779 (95% CI=0.680~0.930) when the cutoff value of ΔEmax was 55.2%. After four cycles, the predictive sensitivity, specificity and AUC of pCR group was 72.3%, 92.0% and 0.831 (95% CI=0.690~0.930) when the cutoff value of ΔEmax was 75.1%. Conclusion:The Emax and ΔEmax values measured by 3D-SWE technology can predict the curative effect of NAC for breast cancer.

Objective:To investigate the clinic value of ultrasound 3-dimensional shear wave elastography (3D-SWE) in therapeutic effect evaluation of neoadjuvant chemotherapy (NAC) for HER-2 positive breast cancer patients.Methods:A total of 43 lesions from 43 HER-2 positive breast cancer patients were selected and all of the lesions were confirmed by biopsy. Ultrasound examination was performed routinely before each chemotherapy cycle. The interested regions were selected under the 3-dimensional (3D) elasticity and gray-scale mode, the relevant data such as shear waves in the transverse, longitudinal and coronal sections of the mass were generated automatically. According to the histopathological results, the patients were divided into the pathological complete remission (pCR) group and the incomplete remission (non-pCR) group. The maximum elastic hardness value (Emax) and the reduction degree (ΔEmax) of the lesions in the two groups were measured and compared in each cycle of NAC. The accuracy of 3D-SWE technique for predicting the efficacy of NAC was evaluated using indicators such as sensitivity, specificity and area under the receiver operating characteristic (ROC) curve.Results:The clinicopathologic features between pCR group (18 cases) and non-pCR Group (25 cases) were not significantly different ( P>0.05). Compared with pre-chemotherapy, the Emax values of pCR group and non-pCR Group during chemotherapy were declined ( P<0.05). Moreover, the Emax values of pCR group before and after chemotherapy were lower than those of non-pCR group ( P<0.05). At the end of the first cycle of chemotherapy, the predictive specificity, sensitivity and area under the curve (AUC) of pCR group were 72.0%, 83.3% and 0.838 (95% CI=0.680~0.930) respectively when the cutoff value of Emax was 118 kPa. At the end of the second cycle, the predictive specificity, sensitivity and AUC of pCR group were 76.0%, 83.3% and 0.863 (95% CI=0.720~0.940) respectively when the cutoff value of Emax was 87 kPa. At the end of the third cycle, the predictive specificity and sensitivity and the AUC of the pCR group were 88.0%, 77.8% and 0.893 (95% CI=0.760~0.970) when the cutoff value of Emax was 57 kPa. At the end of the fourth cycle of chemotherapy, the predictive specificity, sensitivity and AUC of pCR group were 92.5%, 88.9% and 0.960 (95% CI=0.850~0.990) respectively when the cutoff value of Emax was 30 kPa. After one cycle of NAC, the predictive sensitivity and specificity and AUC of pCR group were 88.0%, 60.0%, and 0.719 (95% CI=0.620~0.890) when the cutoff value of ΔEmax was 16.8%. After two cycles, the predictive sensitivity, specificity and AUC of pCR group were 55.5%, 80.0% and 0.712 (95% CI=0.550~0.840) when the cutoff value of ΔEmax was 34.9%. After three cycles, the predictive sensitivity, specificity and AUC of pCR group were 67.4%, 81.2% and 0.779 (95% CI=0.680~0.930) when the cutoff value of ΔEmax was 55.2%. After four cycles, the predictive sensitivity, specificity and AUC of pCR group was 72.3%, 92.0% and 0.831 (95% CI=0.690~0.930) when the cutoff value of ΔEmax was 75.1%. Conclusion:The Emax and ΔEmax values measured by 3D-SWE technology can predict the curative effect of NAC for breast cancer.