BACKGROUND:At present,domestic and foreign studies mainly focus on the comparison of different operation methods for intertrochanteric fracture of femur and the risk of failure in proximal femoral nail antirotation operation.There are few studies on the prognosis of hip function of affected limb after proximal femoral nail antirotation.OBJECTIVE:To analyze the influencing factors of poor hip function recovery in elderly patients with intertrochanteric fracture after proximal femoral nail antirotation surgery,and to construct a score system for predicting hip function after surgery and explore its value.METHODS:A total of 150 patients with intertrochanteric fracture of femur who received proximal femoral nail antirotation surgery in the Affiliated Hospital of Xuzhou Medical University from June 2021 to June 2023 were selected and divided into groups according to the Harris hip function score during postoperative follow-up.A score ≥80 was considered as the good group,and a score＜80 was considered as the poor group.Univariate and binary regression analyses were used to explore the risk factors leading to postoperative hip dysfunction.A score scale was established according to the risk factors.The value of this scoring system in predicting hip function after proximal femoral nail antirotation was investigated by using receiver operating characteristic curve.RESULTS AND CONCLUSION:(1)Among the 150 patients,according to the Harris score standard of the affected hip joint at 1 year follow-up,there were 52 cases in the group with poor functional recovery and 98 cases in the group with excellent functional recovery,with an unsatisfactory rate of 34.7％.(2)The results of univariate comparison between the two groups showed that there were significant differences in age,bone mineral density,number of preoperative underlying complications,type of lateral wall,position of spiral blade,quality of reduction and time of first exercise after surgery between the poor group and the good group(P＜0.05).(3)The results of binary Logistic regression analysis showed:Age ≥75 years old(OR=2.834),osteoporosis(OR=3.002),number of preoperative basic complications＞2(OR=4.024),lateral wall rupture(OR=2.999),position difference of spiral blade(OR=4.025),and time to exercise for the first time after surgery＞4 weeks(OR=3.153)were independent risk factors for hip dysfunction after proximal femoral nail antirotation for the intertrochanteric fractures(P＜0.05);poor reduction quality(OR=1.026)was not an independent risk factor(P＞0.05).(4)Based on the results of binary regression analysis,a score system for predicting good hip function after surgery was established.Receiver operating characteristic curve analysis showed that the threshold for predicting poor hip function after surgery was 4.5 points;the area under the curve was 0.797;the sensitivity was 83.7％and the specificity was 65.4％.(5)These results suggested that age ≥75 years old,osteoporosis,number of preoperative basic comorbidities＞2,lateral wall rupture,poor position of spiral blade,and first time out of bed exercise＞4 weeks after intertrochanteric fracture were risk factors for hip dysfunction after proximal femoral nail antirotation.The establishment of a score prediction system can provide reference value for early clinical identification of high-risk patients with postoperative hip dysfunction,and is conducive to guiding early clinical intervention,adopting more personalized treatment and rehabilitation programs,and promoting the recovery of hip function in patients after surgery.

BACKGROUND:At present,domestic and foreign studies mainly focus on the comparison of different operation methods for intertrochanteric fracture of femur and the risk of failure in proximal femoral nail antirotation operation.There are few studies on the prognosis of hip function of affected limb after proximal femoral nail antirotation.OBJECTIVE:To analyze the influencing factors of poor hip function recovery in elderly patients with intertrochanteric fracture after proximal femoral nail antirotation surgery,and to construct a score system for predicting hip function after surgery and explore its value.METHODS:A total of 150 patients with intertrochanteric fracture of femur who received proximal femoral nail antirotation surgery in the Affiliated Hospital of Xuzhou Medical University from June 2021 to June 2023 were selected and divided into groups according to the Harris hip function score during postoperative follow-up.A score ≥80 was considered as the good group,and a score＜80 was considered as the poor group.Univariate and binary regression analyses were used to explore the risk factors leading to postoperative hip dysfunction.A score scale was established according to the risk factors.The value of this scoring system in predicting hip function after proximal femoral nail antirotation was investigated by using receiver operating characteristic curve.RESULTS AND CONCLUSION:(1)Among the 150 patients,according to the Harris score standard of the affected hip joint at 1 year follow-up,there were 52 cases in the group with poor functional recovery and 98 cases in the group with excellent functional recovery,with an unsatisfactory rate of 34.7％.(2)The results of univariate comparison between the two groups showed that there were significant differences in age,bone mineral density,number of preoperative underlying complications,type of lateral wall,position of spiral blade,quality of reduction and time of first exercise after surgery between the poor group and the good group(P＜0.05).(3)The results of binary Logistic regression analysis showed:Age ≥75 years old(OR=2.834),osteoporosis(OR=3.002),number of preoperative basic complications＞2(OR=4.024),lateral wall rupture(OR=2.999),position difference of spiral blade(OR=4.025),and time to exercise for the first time after surgery＞4 weeks(OR=3.153)were independent risk factors for hip dysfunction after proximal femoral nail antirotation for the intertrochanteric fractures(P＜0.05);poor reduction quality(OR=1.026)was not an independent risk factor(P＞0.05).(4)Based on the results of binary regression analysis,a score system for predicting good hip function after surgery was established.Receiver operating characteristic curve analysis showed that the threshold for predicting poor hip function after surgery was 4.5 points;the area under the curve was 0.797;the sensitivity was 83.7％and the specificity was 65.4％.(5)These results suggested that age ≥75 years old,osteoporosis,number of preoperative basic comorbidities＞2,lateral wall rupture,poor position of spiral blade,and first time out of bed exercise＞4 weeks after intertrochanteric fracture were risk factors for hip dysfunction after proximal femoral nail antirotation.The establishment of a score prediction system can provide reference value for early clinical identification of high-risk patients with postoperative hip dysfunction,and is conducive to guiding early clinical intervention,adopting more personalized treatment and rehabilitation programs,and promoting the recovery of hip function in patients after surgery.

Objective To design and construct a syndrome differentiation knowledge graph that integrates TCM facial color diagnosis information;To explore the hidden relationships between the knowledge.Methods The literature data came from ancient classics,textbooks,as well as standard literature related to inspection included in the CNKI,VIP and Wanfang Data from the establishment of the databases to December 31,2022.The clinical data was sourced from 30 elderly individuals who underwent TCM health examinations at the Community Health Service Center in Jiading Industrial Zone,Shanghai in September 2022.Facial image acquisition was performed using TFDA-1 digital tongue and facial diagnostic instrument.By following the steps of knowledge extraction,knowledge fusion and quality assessment to construct a graph,and with the assistance of TCM experts for interpretation,using Access 2019 to integrate qualitative textual data and quantitative objective image digital information,a syndrome differentiation knowledge graph integrating TCM facial diagnosis was designed and completed in the Neo4j graph database.In addition,a method was designed to shift facial diagnosis knowledge from qualitative to quantitative.Results There were a total of 194 nodes under 8 entity term types and 12 entity term labels,as well as 361 relationships under 13 semantic relationships in knowledge graph.The Neo4j graph database provided a visualized TCM facial color diagnosis and differentiation,which could be queried and fed back using Cypher language.Conclusion The knowledge graph constructed based on the theory of TCM facial color diagnosis visually shows the complex correlation between facial color diagnosis and syndrome differentiation diagnosis,with a knowledge representation model that forms qualitative data of image features → semantic relationships → syndrome differentiation diagnosis forms.

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children′s Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

BACKGROUND:Many studies have shown that total hip arthroplasty will improve low back pain in patients with hip-spine syndrome.However,there are few studies on the relationship between postoperative low back pain improvement and changes in spinal-pelvic sagittal parameters.This study aims to reveal their connections between the two. OBJECTIVE:To explore the relationship between the improvement of low back pain and changes in the spinal-pelvic sagittal parameters in patients with hip-spine syndrome after total hip arthroplasty. METHODS:A retrospective analysis was performed on the clinical and imaging data of 93 end-stage hip disease patients who underwent primary total hip arthroplasty and combined with low back pain and were admitted to Affiliated Hospital of Xuzhou Medical University from January 2019 to January 2022.Spinal-pelvic sagittal parameters were measured on lateral lumbar X-rays before surgery and 1 year at the last follow-up:pelvic incidence,pelvic tilt,sacral slope,lumbar lordosis,pelvic incidence-lumbar lordosis(difference between pelvic incident angle and lumbar lordosis angle).Visual analog scale score,Oswestry disability index,and hip Harris score were recorded before and 1 year after arthroplasty.The patients were divided into two groups according to whether the change in visual analog scale scores 1 year after surgery reached the minimal clinically important difference for low back pain treatment,including 45 cases in the low back pain unimproved group and 48 cases in the low back pain improved group.The preoperative general data of patients,differences in spinal-pelvic sagittal parameters,Oswestry Disability Index and hip Harris score before and after surgery were compared between the two groups. RESULTS AND CONCLUSION:(1)There was no significant difference in age,gender,surgical side,body mass index,and etiology between the two groups(P>0.05),and they were comparable.(2)There was no significant difference in visual analog scale scores before surgery(P>0.05).The visual analog scale scores of the low back pain improved group were lower than those of the low back pain unimproved group 1 year after surgery(P<0.01).(3)At 1 year after surgery,the lumbar lordosis of the low back pain unimproved group was significantly smaller than that before surgery,while the lumbar lordosis of the low back pain improved group was significantly smaller than that before surgery(P<0.01).At the same time,the pelvic incidence-lumbar lordosis mismatch in the low back pain unimproved group was greater than before surgery,while the pelvic incidence-lumbar lordosis mismatch in the low back pain improved group was smaller than before surgery,with significant differences between the two groups(P<0.01).There was no significant difference in the changes of other spinal-pelvic sagittal parameters between the two groups(P>0.05).(4)Preoperative lumbar Oswestry disability index and hip Harris score were not significantly different between the two groups(P>0.05).At 1 year after surgery,Oswestry disability index of the low back pain improved group was lower than that of the low back pain unimproved group and the hip Harris score was higher than that of the low back pain unimproved group(P<0.05).(5)The results showed that the improvement of low back pain was related to changes in spinal-pelvic sagittal parameters in patients with hip-spine syndrome after total hip arthroplasty,showing reduced lumbar lordosis and pelvic incidence-lumbar lordosis mismatch.Moreover,patients with improved low back pain after surgery had better functional scores,indicating that total hip arthroplasty improved spinal alignment and spinal-pelvic sagittal balance.For patients with hip-spine syndrome,a total hip arthroplasty performed before the onset of lumbar disease can have a favorable effect on the lumbar spine.

Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children′s Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

Objective:To investigate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on platelet activation in sepsis.Methods:① Clinical trial: a prospective study was conducted. Patients with sepsis and septic shock aged ≥ 18 years old who met the diagnostic criteria of Sepsis-3 admitted to the department of intensive care medicine of the Affiliated Hospital of Binzhou Medical College from January to October in 2021 were selected as subjects. Healthy subjects in the same period were taken as healthy control group. Platelet count (PLT) in the first routine blood test after admission was recorded. Venous blood was taken 1 day after diagnosis, and serum PCSK9 level was determined by enzyme-linked immunosorbent assay (ELISA). The differences of PCSK9 level and PLT between the two groups were compared, and subgroup analysis was conducted based on PLT for patients with sepsis. The correlation between PCSK9 level and PLT in septic patients was analyzed by Pearson correlation method. ② Animal experiment: 80 male C57BL/6 mice were randomly divided into control group, sepsis model group [lipopolysaccharide (LPS) group], PCSK9 inhibitor pretreatment group (PCSK9 inhibitor+LPS group) and PCSK9 inhibitor control group (PCSK9 inhibitor group), with 20 mice in each group. The mouse model of sepsis was reproduced by intraperitoneal injection of LPS 12 mg/kg, and the control group and PCSK9 inhibitor group were intraperitoneally injected with the same amount of sterile normal saline. PCSK9 inhibitor+LPS group and PCSK9 inhibitor group were pretreated with PCSK9 inhibitor 5 mg/kg intraperitoneal injection for 7 days before injection of LPS or normal saline, respectively, and the control group and LPS group were injected with an equal amount of sterile normal saline. The lung tissues were taken for pathological and immunohistochemical observation 24 hours after modeling. Blood was taken from the heart for determining PLT. Platelet activation was detected by flow cytometry. The expression level of platelet-activation marker CD40L was detected by Western blotting.Results:① Clinical trial: there were 57 cases in the sepsis group and 27 cases in the healthy control group. Serum PCSK9 level in the sepsis group was significantly higher than that in the healthy control group (μg/L: 232.25±72.21 vs. 191.72±54.92, P < 0.05), and PLT was significantly lower than that in the healthy control group [×10 9/L: 146.00 (75.50, 204.50) vs. 224.00 (194.00, 247.00), P < 0.01]. Subgroup analysis showed that the serum PCSK9 level in the thrombocytopenia patients ( n = 20) was significantly higher than that in the non-thrombocytopenia patients ( n = 37; μg/L: 264.04±60.40 vs. 215.06±72.95, P < 0.01). Correlation analysis showed a significant negative correlation between serum PCSK9 levels and PLT in septic patients ( r = -0.340, P = 0.010). ② Animal experiment: there were no significant pathological changes in lung tissue in the control group and PCSK9 inhibitor group under light microscope, and no significant differences in PLT, platelet activation and plasma CD40L protein expression was found between the two groups. In the LPS group, a large number of inflammatory cells were infiltrated in the pulmonary interstitium, the alveolar structure was damaged obviously, the alveolar septum was widened, the alveolar cavity was extensively bleeding, the capillary dilatation with bleeding and platelet aggregation were found, the PLT was significantly decreased, the platelet activation and the expression level of CD40L protein in plasma were significantly increased. The infiltration of inflammatory cells in lung tissue of mice in the PCSK9 inhibitor+LPS group was reduced to a certain extent, the thickening of alveolar septa was reduced, the platelet aggregation in lung tissue was decreased as compared with the LPS group, the PLT was significantly increased (×10 9/L: 515.83±46.60 vs. 324.83±46.31, P < 0.05), the platelet activation and the expression level of CD40L protein in plasma were significantly decreased [positive expression rate of platelet activation dependent granule surface facial mask protein CD62P: (12.15±1.39)% vs. (18.33±2.74)%, CD40L protein (CD40L/β-actin): 0.77±0.08 vs. 1.18±0.10, both P < 0.05]. Conclusion:PCSK9 level has a certain effect on promoting platelet activation in sepsis, and inhibition of PCSK9 level may have potential research value in improving adverse outcomes caused by sepsis thrombocytopenia.

Objective:To investigate the therapeutic effect and safety of pomadomide combined with cyclophosphamide and dexamethasone (PCD) in the treatment of relapsed/refractory multiple myeloma (MM).Methods:The clinical data of 20 relapsed/refractory MM patients receiving PCD regimen in the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College from March 2021 to June 2022 were retrospectively analyzed; and 29 relapsed/refractory MM patients receiving other regimens including DECP (dexamethasone+etoposide+cyclophosphamide+cisplatin, 13 cases) and VCD (bortezomib+ cyclophosphamide+ dexamethasone, 16 cases) during the same period were treated as the control group. The efficacy and adverse effects of both groups were compared after 4 cycles of treatment.Results:After 4 cycles of treatment, the overall response rate (ORR) and the clinical benefit rate (CBR) of 20 cases in PCD group was 70.0% (14/20) and 85.0% (17/20), respectively; among 20 cases, there were 5 cases of complete response (CR), 4 cases of very good partial remission (VGPR), 5 cases of partial remission (PR), 3 cases of minimal remission (MR), 2 cases of stable disease (SD), 1 case of the progression of the disease (PD). ORR and CBR of 29 cases in the control group was 41.4% (12/29) and 65.5% (19/29), respectively; among 29 cases, there were 2 cases of CR, 3 cases of VGPR, 7 cases of PR, 7 cases of MR, 5 cases of SD, 5 cases of PD. There was a statistically significant difference in ORR of both group ( χ2 = 3.89, P = 0.048), while the difference in CBR of both group was not statistically significant ( χ2 = 2.30, P = 0.129). There were 2 patients with renal impairment achieving CR in PCD group and 1 patient with renal impairment achieving CR in the control group ( P = 0.152); 1 genetically high-risk patient achieved CR in PCD group and none of patients in the control group achieved CR, and the difference was statistically significant ( P>0.05). The common hematological adverse effects of two groups were anemia, neutropenia, thrombocytopenia; the common non-hematological adverse effects were malaise, infection and fatigue, and the differences were statistically significant (all P>0.05). The incidence of grade 3-4 infection was 25.0% (5/20) in PCD group and the disease was under the control after anti-infective therapy, and the incidence of grade 3-4 infection was 24.1% (7/29) in the control group; and the difference was not statistically significant ( P > 0.05). Conclusions:PCD regimen has good clinical efficacy and safety in treatment of relapsed/refractory MM.