OBJECTIVE To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice. METHODS Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group： normal control group （normal saline）， epilepsy model group （normal saline）， Jiawei xiaochaihu decoction group [7 g/（kg·d）] and carbamazepine group [positive control， 30 mg/（kg·d）]. Except for the normal control group， the acute epilepsy model was established in the other groups. After successful modeling， mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention， the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected， and the expression levels of protein kinase B （AKT）， Caspase-3， B-cell lymphoma-extra large （Bcl-xL）， Bcl-2-associated X protein （Bax）， as well as the ratio of phosphorylated AKT（p-AKT） to AKT were determined. RESULTS Compared with the normal control group， severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group； the number of TUNEL-positive cells was significantly increased （ P ＜0.05）. The expression levels of p-AKT and Bcl-xL were significantly down-regulated （ P ＜0.05）， while the Bax and Caspase-3 were significantly up-regulated （ P ＜0.05），accompanied by a remarkable decrease of p-AKT/AKT ratio （ P ＜0.05）. Compared with the epilepsy model group， hippocampal tissue ultrastructure， pathological damage， and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group （ P ＜0.05）. CONCLUSIONS Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice， and its mechanism may be related to activating AKT phosphorylation， increasing p-AKT/AKT ratio， up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.

OBJECTIVE To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice. METHODS Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group： normal control group （normal saline）， epilepsy model group （normal saline）， Jiawei xiaochaihu decoction group [7 g/（kg·d）] and carbamazepine group [positive control， 30 mg/（kg·d）]. Except for the normal control group， the acute epilepsy model was established in the other groups. After successful modeling， mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention， the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected， and the expression levels of protein kinase B （AKT）， Caspase-3， B-cell lymphoma-extra large （Bcl-xL）， Bcl-2-associated X protein （Bax）， as well as the ratio of phosphorylated AKT（p-AKT） to AKT were determined. RESULTS Compared with the normal control group， severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group； the number of TUNEL-positive cells was significantly increased （ P ＜0.05）. The expression levels of p-AKT and Bcl-xL were significantly down-regulated （ P ＜0.05）， while the Bax and Caspase-3 were significantly up-regulated （ P ＜0.05），accompanied by a remarkable decrease of p-AKT/AKT ratio （ P ＜0.05）. Compared with the epilepsy model group， hippocampal tissue ultrastructure， pathological damage， and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group （ P ＜0.05）. CONCLUSIONS Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice， and its mechanism may be related to activating AKT phosphorylation， increasing p-AKT/AKT ratio， up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.

Objective:To identify proteins associated with the risk of gastric cancer (GC) and build a protein risk score for risk prediction of GC based on proteomic analysis.Methods:Gastric mucosal proteomics data were used to construct Dataset One, comprising 94 GC cases and 230 individuals with different stages of gastric mucosal lesions. The GC cases were recruited from the National Upper Gastrointestinal Cancer Early Detection (UGCED) Program in Linqu, Shandong Province, as well as clinical patients from the Fifth Medical Center, General Hospital of PLA, and Peking University Cancer Hospital. Non-cancer individuals were enrolled from the National UGCED Program in Linqu and community screening programs at the Dongfang Hospital. All participants were pathologically confirmed. Multivariate logistic regression analysis was employed to identify gastric mucosal proteins significantly associated with GC risk. Subsequently, plasma proteomics data from the UK Biobank Pharma Proteomics Project (UKB-PPP) were used to construct Dataset Two, including 40 baseline GC cases and 47 933 non-cancer individuals, and Dataset Three, comprising 138 incident GC cases and 47 933 non-cancer individuals during a prospective follow-up period. In Dataset Two, multivariate logistic regression analysis was conducted to assess associations between plasma protein levels and baseline GC risk. In Dataset Three, multivariate Cox regression analysis was used to examine associations with the risk of incident GC. A poly-protein risk score (PRS) was developed using a weighted summation method based on protein effect sizes from Dataset Two. Its associations with GC risk and the progression of gastric mucosal lesions were evaluated using linear regression trend tests.Results:A total of 324, 47 973 and 48 071 participants were included in Datasets One, Two, and Three, respectively. Across the three datasets, the proportions of males and individuals aged>60 years were higher in the GC group than in the non-GC group (all P values<0.05). The follow-up period in Dataset Three had a M ( P 25, P 75) of 14.47 (13.7, 15.2) years, with a median of 7.4 (4.6, 11.3) years for those who progressed to GC. Based on Dataset One, 2 524 tissue-differential proteins associated with GC risk were identified through multivariate logistic regression analysis adjusted for age and sex. Among these, seven proteins were consistently associated with GC risk across tissue and plasma levels in Datasets Two and Three, with consistent directions of association. Five proteins (MRC1, APOL1, BST2, PON2, and GGH) were positively associated with GC risk, while two (GSN and CLEC3B) were negatively associated. Analysis of the PRS based on these seven proteins showed that for each standard deviation increase in the tissue-derived PRS, the risk of GC increased by 6.26 times (95% CI: 4.02-9.75). In Dataset Two, each standard deviation increase in the plasma-derived PRS was associated with a 2.13-fold increase in GC risk (95% CI: 1.68-2.69). In the prospective cohort of Dataset Three, individuals in the high PRS group had a 2.27-fold higher risk of GC compared to the low PRS group (95% CI: 1.50-3.45). Moreover, each standard deviation increase in the plasma PRS was associated with a 57% higher risk of GC ( HR=1.57, 95% CI: 1.34-1.84). Additionally, the tissue-derived PRS showed an increasing trend with the progression of gastric mucosal lesions. Conclusion:The tissue and plasma proteomics identified seven individual proteins that may indicate the risk of developing gastric cancer, showing the potential as biomarkers for aiding in the screening of gastric cancer.

Temporomandibular joint osteoarthritis is a common chronic degenerative disease,in which joint pain is the most signif-icant symptom,but its pathogenesis is still unclear.Significant subchondral bone lesions can occur in the early stage of osteoarthritis progression,and more and more experimental evidence shows that subchondral bone lesions play an important role in the pain caused by osteoarthritis.Osteoclasts,osteocytes,osteoblasts,endothelial cells,new generating nerves and blood vessels in the sub-chondral bone matrix microenvironment interact with each other and participate in the process of osteoarthritis pain.Therefore,regu-lating the subchondral bone matrix microenvironment is expected to become a new strategy to control joint pain.

BACKGROUND:Mechanical alignment is the"gold standard"alignment technique in total knee arthroplasty,but regardless of advances in prosthetic materials and robotic-assisted navigation,mechanical alignment-total knee arthroplasty still has a patient dissatisfaction rate of about 20％.OBJECTIVE:To evaluate the early efficacy of navigation-assisted total knee arthroplasty using functional alignment.METHODS:A total of 44 consecutive cases(50 knees)that underwent computer navigation-assisted total knee arthroplasty with functional alignment from October 2019 to June 2023 were retrospectively analyzed,including 12 males(14 knees)and 32 females(36 knees).A total of 46 consecutive cases(50 knees)that underwent navigation-assisted total knee arthroplasty with mechanical axis alignment by the same surgical team during the same period were selected as controls,including 5 males(5 knees)and 41 females(45 knees).The tibial osteotomy angle,tibial plateau osteotomy amount,femoral osteotomy angle,distal femoral,posterior and anterior osteotomy amount,and joint line movement were observed in the two groups of patients.Preoperative and postoperative flexion and extension gap internal and external laxity,hip-knee-ankle angle,mechanical lateral distal femoral angle,mechanical medial proximal tibial angle,joint line convergence angle,sagittal femoral component angle,posterior tibial slope,arithmetic hip-knee-ankle angle,joint line obliquity,coronal plane alignment of the knee classification,Western Ontario and McMaster Universities Osteoarthritis Index,and Hospital for Special Surgery score and forgotten joint score were compared between the two groups.RESULTS AND CONCLUSION:(1)The intraoperative tibial plateau osteotomy angle in the functional alignment group was greater than that in the mechanical axis alignment group,and the proportion of gap imbalance(2％)was smaller than that in the mechanical axis alignment group(18％).The differences were all significant(P＜0.05).(2)The hip-knee-ankle angle,mechanical medial proximal tibial angle,arithmetic hip-knee-ankle angle,and joint line obliquity in the functional alignment group were smaller than those in the mechanical axis alignment group postoperatively,and the differences were significant(P＜0.05).(3)The most common coronal plane alignment of the knee classification before surgery was type Ⅰ(80％in the functional alignment group and 42％in the mechanical axis alignment group).(4)The proportion of joint line obliquity＜177°(44％)in the functional alignment group was greater than that in the mechanical axis alignment group(14％)postoperatively.(5)Hospital for Special Surgery score at 1 month,6 months,and last follow-up after surgery was higher in the functional alignment group than that in the mechanical axis alignment group;the differences were statistically significant(P＜0.05).The Western Ontario and McMaster Universities Osteoarthritis Index 1 month after surgery was lower in the functional alignment group than that in the mechanical axis alignment group;the difference was statistically significant(t=-2.85,P=0.005).There was no significant difference in postoperative range of motion and forgotten joint score between the two groups(P＞0.05).(6)It is indicated that navigation-assisted total knee arthroplasty using functional alignment optimizes early clinical efficacy.The functional alignment technique has advantages in restoration of constitutional alignment and joint line obliquity and avoids soft tissue release compared to mechanical alignment technique.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Objective:To identify proteins associated with the risk of gastric cancer (GC) and build a protein risk score for risk prediction of GC based on proteomic analysis.Methods:Gastric mucosal proteomics data were used to construct Dataset One, comprising 94 GC cases and 230 individuals with different stages of gastric mucosal lesions. The GC cases were recruited from the National Upper Gastrointestinal Cancer Early Detection (UGCED) Program in Linqu, Shandong Province, as well as clinical patients from the Fifth Medical Center, General Hospital of PLA, and Peking University Cancer Hospital. Non-cancer individuals were enrolled from the National UGCED Program in Linqu and community screening programs at the Dongfang Hospital. All participants were pathologically confirmed. Multivariate logistic regression analysis was employed to identify gastric mucosal proteins significantly associated with GC risk. Subsequently, plasma proteomics data from the UK Biobank Pharma Proteomics Project (UKB-PPP) were used to construct Dataset Two, including 40 baseline GC cases and 47 933 non-cancer individuals, and Dataset Three, comprising 138 incident GC cases and 47 933 non-cancer individuals during a prospective follow-up period. In Dataset Two, multivariate logistic regression analysis was conducted to assess associations between plasma protein levels and baseline GC risk. In Dataset Three, multivariate Cox regression analysis was used to examine associations with the risk of incident GC. A poly-protein risk score (PRS) was developed using a weighted summation method based on protein effect sizes from Dataset Two. Its associations with GC risk and the progression of gastric mucosal lesions were evaluated using linear regression trend tests.Results:A total of 324, 47 973 and 48 071 participants were included in Datasets One, Two, and Three, respectively. Across the three datasets, the proportions of males and individuals aged>60 years were higher in the GC group than in the non-GC group (all P values<0.05). The follow-up period in Dataset Three had a M ( P 25, P 75) of 14.47 (13.7, 15.2) years, with a median of 7.4 (4.6, 11.3) years for those who progressed to GC. Based on Dataset One, 2 524 tissue-differential proteins associated with GC risk were identified through multivariate logistic regression analysis adjusted for age and sex. Among these, seven proteins were consistently associated with GC risk across tissue and plasma levels in Datasets Two and Three, with consistent directions of association. Five proteins (MRC1, APOL1, BST2, PON2, and GGH) were positively associated with GC risk, while two (GSN and CLEC3B) were negatively associated. Analysis of the PRS based on these seven proteins showed that for each standard deviation increase in the tissue-derived PRS, the risk of GC increased by 6.26 times (95% CI: 4.02-9.75). In Dataset Two, each standard deviation increase in the plasma-derived PRS was associated with a 2.13-fold increase in GC risk (95% CI: 1.68-2.69). In the prospective cohort of Dataset Three, individuals in the high PRS group had a 2.27-fold higher risk of GC compared to the low PRS group (95% CI: 1.50-3.45). Moreover, each standard deviation increase in the plasma PRS was associated with a 57% higher risk of GC ( HR=1.57, 95% CI: 1.34-1.84). Additionally, the tissue-derived PRS showed an increasing trend with the progression of gastric mucosal lesions. Conclusion:The tissue and plasma proteomics identified seven individual proteins that may indicate the risk of developing gastric cancer, showing the potential as biomarkers for aiding in the screening of gastric cancer.

Objective To observe the effect of resveratrol on intestinal ischemia reperfusion(IIR)inju-ry and its correlation with ferroptosis.Methods The mice IIR injury model was constructed.The mice were divided into the sham operation group(group S),IIR injury group(group D),IIR injury+resveratrol group(group R),IIR injury+ferroptosis inducer group(group F),IIR injury treatment+resveratrol+ferropto-sis inducer group(group R+F).The various groups adopted different drug doses and methods.The intestinal tissue sections were taken for performing the HE staining and the pathological changes were observed by the light microscope.ELISA was used to detect the levels of malondialdehyde(MDA),ferrous ion(Fe2+),gluta-thione(GSH)and super oxide dismutase(SOD).Western blot was used to detect the expression levels of glu-tathione peroxidase 4(GPX4)and acyl-coasynthetasling-chain family member 4(ACSL4)protein.Results Com-pared with the group S,the small intestine tissue damage in the group D,R,F and R+F was aggravated,the Chiu's score,MDA and Fe2+level s were increased,GSH and SOD levels were decreased(P＜0.05),the AC-SL4 protein expression was up-regulated,GPX4 protein expression was down-regulated,and the differences were statistically significant(P＜0.05).Compared with the group D,the small intestine tissue in the group R appeared subapical villous injury,Chiu's score,MDA and Fe2+levels were decreased,the GSH and SOD levels were increased,the ACSL4 protein expression was down-regulated and GPX4 protein expression was up-regu-lated,and the differences were statistically significant(P＜0.05);the small intestine tissue in the group F ap-peared villi fall off accompanied by bleeding and ulcer formation,Chiu's score,MDA level and Fe2+level were increased,GSH and SOD levels were decreased,ACSL4 protein expression level was up-regulated,GPX4 pro-tein expression was down-regulated,and the differences were statistically significant(P＜0.05).Compared with the R group,the small intestine tissue in the R+F group appeared a large number of villi and lamina pro-pria,which were damaged and fell off,Chiu's score,MDA and Fe2+levels were increased,GSH and SOD lev-els were decreased,ACSL4 protein expression was up-regulated and GPX4 protein expression was down-regu-lated,and the differences were statistically significant(P＜0.05).Conclusion Resveratrol may alleviate intes-tinal injury caused by IIR through antioxidation action and inhibiting ferroptosis.

Objective:To develop the Amputation Scale for Severe Open Pelvic Fractures and explore its application value in patients with severe open pelvic fractures.Methods:A total of 27 patients with severe open pelvic fractures who underwent surgical treatment in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2010 to January 2023 were retrospectively analyzed. There were 15 males and 12 females, aged 38.6±11.6 years (range, 13-65 years). There were 13 cases of traffic injuries, 10 cases of fall from height injuries, and 4 cases of mechanical crushing injuries; 20 cases were admitted to the hospital in emergency, and 7 cases were transferred from other hospitals. All fracture types were Tile C, including 14 cases of Tile C1, 8 cases of Tile C2, and 5 cases of Tile C3. There were 16 cases of genitourinary system injury, 8 cases of anal or rectal injury, 12 cases of abdominal injury, 9 cases of chest injury, and 6 cases of craniocerebral trauma. The mangled extremity severity score (MESS) and the Amputation Scale for Severe Open Pelvic Fractures were used to evaluate whether amputation was performed. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the two evaluation methods were calculated.Results:Among the 27 patients, 21 cases were treated with pelvic external fixator to control the volume, 16 cases were treated with gauze packing to stop bleeding, 8 cases were treated with temporary abdominal aorta occlusion, and 12 cases were treated with laparotomy because of abdominal injury. Seven of the 27 patients died, with a mortality rate of 26%. In 12 cases of one-stage amputation, 3 cases died, including 1 case died of multiple organ failure syndrome, 1 case died of gastrointestinal bleeding on the 7th day after amputation, and 1 case died of severe infection on the 4th day after amputation. Among the 15 cases of one-stage limb salvage, 4 cases died, of which 2 cases of second-stage amputation died of infection on the 5th day after one-stage limb salvage, and 1 case of one-stage limb salvage died of limb necrosis on the 3rd day after one-stage limb salvage. Two patients died of multiple organ failure syndrome. The MESS score of 27 patients was 6(6, 8) points (range, 6-13 points), and the Amputation Scale for Severe Open Pelvic Fractures score was 9.6±1.8 points (range, 6-14 points). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MESS were 66.7%, 50%, 40%, 75% and 56%, respectively, while those of Amputation Scale for Severe Open Pelvic Fractures were 80%, 89%, 73%, 88% and 82%, respectively. The specificity and accuracy of MESS were significantly lower than those of Amputation Scale for Severe Open Pelvic Fractures ( P<0.05). All 20 patients who survived were followed up for 23.6±7.5 months (range, 11-37 months). Five cases had soft tissue infection at the stump of amputation, which were treated with debridement, and 3 cases underwent skin grafting, and the stump healed well at the last follow-up. Conclusion:The Amputation Scale for Severe Open Pelvic Fractures is better than MESS in the assessment of early amputation in patients with severe pelvic fractures.

Objective:To develop the Amputation Scale for Severe Open Pelvic Fractures and explore its application value in patients with severe open pelvic fractures.Methods:A total of 27 patients with severe open pelvic fractures who underwent surgical treatment in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2010 to January 2023 were retrospectively analyzed. There were 15 males and 12 females, aged 38.6±11.6 years (range, 13-65 years). There were 13 cases of traffic injuries, 10 cases of fall from height injuries, and 4 cases of mechanical crushing injuries; 20 cases were admitted to the hospital in emergency, and 7 cases were transferred from other hospitals. All fracture types were Tile C, including 14 cases of Tile C1, 8 cases of Tile C2, and 5 cases of Tile C3. There were 16 cases of genitourinary system injury, 8 cases of anal or rectal injury, 12 cases of abdominal injury, 9 cases of chest injury, and 6 cases of craniocerebral trauma. The mangled extremity severity score (MESS) and the Amputation Scale for Severe Open Pelvic Fractures were used to evaluate whether amputation was performed. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the two evaluation methods were calculated.Results:Among the 27 patients, 21 cases were treated with pelvic external fixator to control the volume, 16 cases were treated with gauze packing to stop bleeding, 8 cases were treated with temporary abdominal aorta occlusion, and 12 cases were treated with laparotomy because of abdominal injury. Seven of the 27 patients died, with a mortality rate of 26%. In 12 cases of one-stage amputation, 3 cases died, including 1 case died of multiple organ failure syndrome, 1 case died of gastrointestinal bleeding on the 7th day after amputation, and 1 case died of severe infection on the 4th day after amputation. Among the 15 cases of one-stage limb salvage, 4 cases died, of which 2 cases of second-stage amputation died of infection on the 5th day after one-stage limb salvage, and 1 case of one-stage limb salvage died of limb necrosis on the 3rd day after one-stage limb salvage. Two patients died of multiple organ failure syndrome. The MESS score of 27 patients was 6(6, 8) points (range, 6-13 points), and the Amputation Scale for Severe Open Pelvic Fractures score was 9.6±1.8 points (range, 6-14 points). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MESS were 66.7%, 50%, 40%, 75% and 56%, respectively, while those of Amputation Scale for Severe Open Pelvic Fractures were 80%, 89%, 73%, 88% and 82%, respectively. The specificity and accuracy of MESS were significantly lower than those of Amputation Scale for Severe Open Pelvic Fractures ( P<0.05). All 20 patients who survived were followed up for 23.6±7.5 months (range, 11-37 months). Five cases had soft tissue infection at the stump of amputation, which were treated with debridement, and 3 cases underwent skin grafting, and the stump healed well at the last follow-up. Conclusion:The Amputation Scale for Severe Open Pelvic Fractures is better than MESS in the assessment of early amputation in patients with severe pelvic fractures.