Objective To construct a prognostic model of future asthma exacerbation risk in adults by com-bining novel biomarkers of serum chitinase-3-like protein 1(YKL-40),dipeptidyl peptidase-4(DPP4)and conventional predictors.Methods Patients with asthma in the non-acute exacerbation phase were recruited from the People's Hospital of Yubei District of Chongqing,from March 2022 to May 2023.Baseline clinical da-ta collected included medical history,forced expiratory volume in the first second(FEV1)/forced vital capacity(FVC),percentage of predicted forced expiratory volume in the first second(FEV1％pred),blood eosinophil count(EOS),blood neutrophil count(NEU),fractional exhaled nitric oxide(FeNO),serum YKL-40,and ser-um DPP4,etc.The patients were followed for one year to gather data on asthma acute exacerbations and their timings as defined in this study.A COX proportional hazards regression model was used to construct a prog-nostic model for future asthma exacerbations,with internal validation and results presentation.Results A to-tal of 224 patients with asthma completed the study.During the one-year follow-up period,102 patients experi-enced acute exacerbations as defined in this study.Based on univariate COX regression,stepwise regression for variable selection,clinical significance,and model simplicity,asthma control test(ACT)score group,number of asthma exacerbations in the past year group,log10(YKL-40),log10(FeNO),log10(EOS),and FEV1％pred were the following predictors were included in the final model.The overall C-statistic of the model was 0.795(95％CI:0.754-0.836),the area under the curve at the 52-week follow-up was 0.879(95％CI:0.834-0.924),and the Brier score at the 52-week follow-up was 0.142(95％CI:0.117-0.168).The calibration curve was close to a slope of 1,and bootstrap validation suggested good stability of the prediction model.The model was presented using a Nomogram and a dynamic scoring table in a web APP,which can be used to predict the risk of asthma exacerbations within 52 weeks for individual patients.Conclusion The prediction model based on serum YKL-40,EOS,FeNO,the number of asthma exacerbation in the past year group,FEV1％pred and ACT scores group can accurately predict the probability of acute attacks in 52 weeks of asthma patients.

Malignant tumors(commonly referred to as cancer)represent a major global public health challenge and contribute significantly to the worldwide disease burden.Early screening plays a critical role in improving detection rates,enabling timely intervention,and enhancing pa-tient survival rates.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifical-ly rational,multi-cancer screening approach offers several advantages:it optimizes the use of bio-logical samples,reduces time costs for participants,enhances the efficiency and comprehensive-ness of screening,and minimizes overall expenses.Such an approach also facilitates the rational allocation of healthcare resources,ultimately helping to reduce the societal burden of cancer.To address this need,the Cancer Epidemiology Committee of the Chinese Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers in China.This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and interna-tional researches on cancer screening,early detection,and treatment for prevalent malignancies.Drawing upon China's unique demographic and healthcare context,as well as practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the principles and methodologies established by the World Health Organization(WHO),aiming to:enhance the effectiveness of combined cancer screening in China,improve early detec-tion rates,and provide a scientific foundation for national cancer prevention and control strategies.

Malignant tumors(commonly referred to as cancers)represent a major global public health challenge and contribute substan-tially to the global disease burden.Early screening plays a crucial role in improving detection rates,enabling timely intervention,and enhan-cing patient survival.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifically rational,multi-cancer screening approach offers several advantages:it optimizes the use of biological samples,reduces the time burden for participants,enhances the efficiency and comprehensiveness of screening,and min-imizes overall expenses.Moreover,this approach facilitates rational allocation of healthcare resources,ultimately helping to reduce the soci-etal burden of cancer.To address gap,the Cancer Epidemiology Committee of the China Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers.This consensus integrates multidisciplinary expertise and synthesizes the latest do-mestic and international researches on cancer screening,early detection,and treatment of prevalent malignancies.Drawing upon China's unique demographic and healthcare context and practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the prin-ciples and methodologies established by the World Health Organization(WHO),aiming to enhance the effectiveness of combined cancer screening in China,improve early detection rates,and provide a scientific foundation for national cancer prevention and control strategies.

The exploration of pathogenic single nucleotide polymorphisms in the genome plays a pivotal role in the study of human disease-associated genetic mutations. However, there remains a lack of suitable high-throughput screening platforms to investigate the impact of point mutations on genomic structure and function. CRISPR/Cas9-mediated base editors has enabled large-scale annotation of the human genome and phenotypic characterization of monogenic genetic disorders. Base editors, a precise gene-editing technology capable of achieving targeted base substitutions, can be employed to induce mutations at specific functional sites, thereby observing their effects on gene expression, protein function, and cellular phenotypes. Furthermore, integrating base editors with high-throughput screening technologies allows for the large-scale evaluation of multiple candidate sites, accelerating the identification of functional loci and providing a powerful tool for disease research and therapeutic target discovery. This article aims to introduce the working principles of various base editors, including cytosine base editors, adenine base editors, and prime editors, and summarize recent advances in high-throughput screening of functional genomic sites using base-editing techniques.

Objective:To investigate the neural regulatory mechanism of parvalbumin-positive interneurons(PV-INs)in the dentate gyrus(DG)involved in the impairment of spatial recognition memory by exercise-induced chronic fatigue.Methods:Male Sprague-Dawley(SD)rats were divided into control group and fatigue group by random num-ber method.A three-level incremental load treadmill training program was selected to establish a chronic exhaustion exercise fatigue model.The spatial recognition memory ability of rats was tested by novel object recognition test.The ac-tivation levels and quantitative changes of astrocytes(AS)and PV-INs in the DG region was observed and quantified through immunofluorescence staining and immunohistochemical staining.The phosphorylation level of calcium/calmodu-lin-dependent protein kinase Ⅱ(CaMK Ⅱ)in the hippocampus was detected by Western blot.Results:In the test of novel object recognition,the exploration time of novel object was reduced in the fatigue group,and the discrimination index was significantly lower than that in the control group(P＜0.01).Immunohistochemical staining showed that PV-INs in the DG region of fatigue rats were lighter and fewer than those in the control group,the fibers were short and sparse,and the positive cell density and average optical density of cells were significantly lower than those in the control group(P＜0.01).Immunofluorescence staining showed that AS was significantly activated,glial fibrillary acidic pro-tein(GFAP)was stained deeply,and the cell processes were dense and elongated in the DG region of fatigue rats.The positive cell density and mean fluorescence intensity were significantly higher than those of the control group(P＜0.01).The results of Western blot showed that the phosphorylation level of CaMK Ⅱ protein in the hippocampus of the fatigue group was significantly reduced than that of the control group(P＜0.01).Conclusion:Exercise-induced chro-nic fatigue inhibited PV-INs in the rat hippocampal DG region.The excessive activation of AS following exercise fatigue may be a major contributor to this PV-INs suppression.Concurrently,reduced phosphorylation levels of CaMK Ⅱ protein were observed in hippocampal tissue.These alterations ultimately impaired spatial recognition memory in the rats.

Objective:To explore the establishment, implementation, and application effect of the annual progressive assessment mode for standardized training of resident physicians in a medical laboratory base.Methods:Since 2020, the base has improved the annual progressive assessment system through assessment system establishment, question bank construction, routine assessment, rotation examination, and annual examination. This new assessment mode was adopted for the residency trainees enrolled in the base after 2020. The control group consisted of seven residency trainees enrolled before 2020, while the experimental group comprised 13 trainees enrolled in 2020 and later. The two groups were compared based on the rotation and annual examination scores of second- and third-year trainees, as well as their academic achievements. Additionally, teaching outcomes of the base before and after 2020 were analyzed. The t test, rank-sum test, and Fisher's exact test were performed using SPSS 27.00. Results:There were no significant differences in age, sex, and education level between the two groups. The experimental group showed significantly higher scores than the control group in theory assessment ( P<0.001 for second-year trainees and P=0.008 for third-year trainees) and skill assessment ( P<0.001 for second-year trainees and P=0.038 for third-year trainees) in rotation examination, as well as in theory assessment (both P<0.001) and skill assessment (both P<0.001) in annual examination. The improvement was particularly pronounced among second-year trainees. The trainees of the experimental group submitted 17 case reports in three years, and won awards at national conferences, provincial conferences, and institutional case speech competitions. In a national academic conference, the trainees won the second prize of "Excellent Case". Since 2020, we have been granted with our first teaching reform project and published our first teaching article. To date, we have obtained five teaching reform projects, published six teaching articles, and won multiple awards in provincial and institutional teaching competitions. Conclusions:The establishment of the annual progressive assessment mode is critical for training high-quality laboratory physicians, and puts forward higher requirements for residency training teachers.

The exploration of pathogenic single nucleotide polymorphisms in the genome plays a pivotal role in the study of human disease-associated genetic mutations. However, there remains a lack of suitable high-throughput screening platforms to investigate the impact of point mutations on genomic structure and function. CRISPR/Cas9-mediated base editors has enabled large-scale annotation of the human genome and phenotypic characterization of monogenic disorders. Base editors, a precise gene-editing technique capable of achieving targeted base substitutions, can be employed to induce mutations at specific functional sites, thereby observing their effects on gene expression, protein function, and cellular phenotypes. Furthermore, integrating base editors with high-throughput screening technologies allows for large-scale evaluation of multiple candidate sites, accelerating the identification of functional loci and providing a powerful tool for disease research and therapeutic target discovery. This article aims to introduce the working principles of various base editors, including cytosine base editors, adenine base editors, and prime editors, and summarize recent advances in high-throughput screening of functional genomic sites using base-editing techniques.
Humans ; Gene Editing/methods* ; CRISPR-Cas Systems/genetics* ; Genome, Human ; Polymorphism, Single Nucleotide

Objective:To evaluate the effects of a reduced-positioning restrictions nursing program on postoperative recovery, sleep quality, self-care ability, and hip joint function in patients undergoing total hip arthroplasty (THA), providing a reference for postoperative positioning management.Methods:A randomized controlled trial was conducted, and 140 THA patients admitted to Zhejiang Provincial People′s Hospital from January 2022 to June 2023 were selected using convenience sampling. They were divided into a control group (70 cases) and an observation group (70 cases) using a random number table. The control group received conventional rehabilitation care, while the observation group received a reduced-positioning restrictions nursing program in addition to the conventional care. The incidence of dislocation at 3 months postoperatively, the activities of daily living, the hip joint function recovery at 1 month and 3 months postoperatively, the sleep quality at 1 month postoperatively were compared between the two groups.Results:Finally 63 cases in the control group and 64 cases in the observation group completed the study. The control group included 25 males and 38 females, with an average age of (65.44 ± 10.97) years, while the observation group included 28 males and 36 females, with an average age of (65.13 ± 12.18) years. At 3 months postoperatively, there was no significant difference in the dislocation rate between the control group and the observation group ( P>0.05). At 1 month and 3 months postoperatively, the scores of activities of daily living in the observation group were (77.89 ± 6.71) and (93.52 ± 6.59) points respectively, which were higher than those in the control group [(69.68 ± 5.53) and (87.38 ± 7.72) points], the differences were statistically significant ( t=5.38, 6.96, both P<0.05), the time, interaction and inter-group effects were all statistically significant ( F=33.93, 10.81, 876.91, all P<0.05). At 1 month postoperatively, the excellent and good rate of hip joint function score grade in the observation group was 73.44% (47/64), which was higher than 41.27% (26/63) in the control group, the difference was statistically significant ( Z=-3.67, P<0.05), there was no statistically significant difference between the two groups at 3 months postoperatively ( P>0.05). At 1 month after the operation, the excellent and good rate of sleep quality score grades in the observation group was 81.25% (52/64), which was higher than 57.14% (36/63) in the control group, and the difference was statistically significant ( Z=-3.00, P<0.05). Conclusions:Incorporating a reduced-positioning restrictions nursing program into the perioperative management of THA does not increase the risk of prosthesis dislocation. This approach enhances patient comfort, improves sleep quality, increases self-care ability, and supports the recovery of hip joint function.

Objective:To explore the effect of behavioral activation therapy on subthreshold depression and quality of life in patients with diabetes foot amputation, and to provide reference for clinical psychotherapy and quality of life improvement in patients with diabetes foot amputation.Methods:A randomized controlled trial was conducted to select 50 patients with diabetes foot amputation from September to December 2023 in the People′s Hospital Affiliated to Shandong First Medical University by convenient sampling. The participants were divided into an control group and a observation group, with 25 cases in each group, using a random number table method. The patients in the control group received routine nursing care of diabetes feet, and the patients in the observation group were given behavior activation therapy on the basis of the control group. The Centre for Epidomiological Studies Depression Scale (CES-D), Behavioral Activation for Depression Scale-Short Form (BADS-SF), and Short Form Health Measure (SF-12) were used to assess patients′ subthreshold depression, behavior, and quality of life before the intervention, at the end of the intervention, and 3 months after the intervention.Results:The final number of patients who completed the study in the control group and observation group were 23 and 24, respectively. There were 11 males and 12 females in the control group, with an age of (69.70 ± 7.01) years. There were 12 males and 12 females in the observation group, with an age of (69.17 ± 6.83) years. At the end of the intervention and 3 months after the intervention, the CES-D scores of the observation group were (21.13 ± 2.19) and (18.83 ± 1.86) points, respectively, which were significantly lower than those of the control group (25.70 ± 1.72) and (25.91 ± 1.65) points, and the differences were statistically significant ( t=-7.93, -13.80, both P<0.05). At the end of the intervention and 3 months after the intervention, the BADS-SF behavioral activation dimension scores in the observation group were (17.67 ± 2.41) and (18.50 ± 2.19) points, respectively, higher than the control group's (11.83 ± 1.78) and (11.57 ± 2.02) points, and the differences were statistically significant ( t=31.65, 34.45, both P<0.05). The behavioral avoidance dimension scores were (9.48 ± 1.50) and (9.65 ± 1.99) points, respectively, lower than the control group's (10.75 ± 1.42) and (11.88 ± 1.57) points, and the differences were statistically significant ( t=6.53, 13.17, both P<0.05). Three months after the intervention, the total score of SF-12 in the observation group was (65.96 ± 2.94) points, and the psychological dimension score was (37.50 ± 4.14) points, both of which were higher than those in the control group (60.30 ± 2.42) and (30.13± 5.15) points, and the differences were statistically significant ( t=51.54, 5.42, both P<0.05). There were statistically significant differences in time, between groups, and interaction effects in CES-D score, scores of two dimensions of BADS-SF and SF-12 total score ( F values were 10.04-190.71). Conclusions:Behavioral activation therapy can improve the symptoms of subthreshold depression in patients with diabetes foot amputation, enhance their behavioral activation level, and improve the quality of life to a certain extent.

Objective:To explore the consistency of claudin 18.2 immunohistochemistry (IHC) using 4 different clone antibodies in gastric adenocarcinoma.Methods:A total of 226 gastric adenocarcinomas diagnosed and treated at the Drum Tower Hospital Affiliated to Nanjing University Medical College between January 2022 to March 2023 were included in this study. The cohort consisted of 165 males and 61 females, with a mean age of (61.3±12.1) years. Tumor tissues from radical resection specimens were collected for tissue microarrays. IHC detection of claudin 18.2 was performed using the EnVision method, utilizing 4 clones of antibody: OTIR157B5, 43-14A, EPR19202 and D313D22. The results were interpreted based on both the intensity of staining on tumor cell membranes and the percentage of positive tumor cells relative to the total tumor cells.Results:The positive cutoff value was set as moderately to strongly linear membrane staining in ≥75% of all viable invasive tumor cells, and clone OTIR157B5 demonstrated the highest positive expression rate at 52.2% (118/226). Additionally, the clones OTIR157B5, 43-14A, and EPR19202 were consistently and strongly positive, with all agreement rates of Cohen κ exceeding 0.8. In gastric adenocarcinoma and its three Lauren subtypes, OTIR157B5 exhibited clear membranous localization.Conclusions:Clone OTIR157B5 of claudin 18.2 antibody shows the highest rate of moderately to strongly linear membrane-positive staining, accounting for ≥75% of all viable invasive tumor cells, and clones 43-14A and EPR19202 show strong consistency and high sensitivity.