OBJECTIVE To investigate the improvement effects and mechanism of Achyranthes bidentata total saponins （ABS） extract on vascular endothelial dysfunction in spontaneously hypertensive rat （SHR） based on cytochrome P450 4A （CYP4A）/20-hydroxyeicosatetetraenoic acid （20-HETE）/G protein-coupled receptor 75 （GPR75） axis. METHODS Ten Wistar- Kyoto rats were taken as the normal control group. Forty SHR were first stratified by systolic blood pressure and then， within each stratum， randomly assigned using a random-number table to the model group （MOD group）， captopril positive control group （CAP group， 10 mg/kg）， ABS low- and high-dose extract groups （ABS-L group， ABS-H group， 60 and 120 mg/kg）， with 10 rats in each group. Animals in each group were given the corresponding drug or equal volume of pure water by gavage， once a day， for 28 consecutive days. After the last administration， systolic blood pressure of rats was measured. The levels of vasoactive substances， inflammatory factors and oxidative stress indicators in serum were measured. The pathological changes of rat thoracic aorta were observed. The level of reactive oxygen species （ROS） in aortic tissue was analyzed. The expressions of endothelial nitric oxide synthase （eNOS）， CYP4A， GPR75， nuclear factor-κB p65 （NF-κB p65）， phosphorylated NF-κB p65， p22phox， and reduced nicotinamide adenine dinucleotide phosphate oxidase 4（NOX4） in thoracic aorta tissue were detected. RESULTS After 28 d of treatment， compared with MOD group， the systolic blood pressure of rats in the ABS-L and ABS-H groups decreased significantly. The levels of 20-HETE， angiotensin Ⅱ， interleukin-1β， interleukin-6， tumor necrosis factor-α， intercellular cell adhesion molecule-1 and malondialdehyde in serum were significantly reduced （P＜0.05 or P＜0.01）， while the levels of nitric oxide， superoxide dismutase， glutathione peroxidase and catalase were significantly increased （P＜0.05 or P＜0.01）. Intimal damage of thoracic aorta was reduced， and endothelial cell morphology was improved. The expressions of ROS， CYP4A， GPR75， p22phox， NOX4 and the phosphorylation level of NF-κB p65 protein in thoracic aorta were down-regulated or reduced （P＜0.05 or P＜0.01）， while the expression of eNOS was up-regulated （P＜0.05 or P＜0.01）. CONCLUSIONS ABS extract may alleviate the inflammatory response and oxidative stress in SHR effectively by down-regulating the expression of CYP4A， reducing the production of 20-HETE， inhibiting the activation of GPR75， and subsequently suppressing the activation of downstream NF-κB and NOX4， thereby improving hypertension-related vascular endothelial dysfunction.

Objective:To compare postoperative inflammatory markers and surgical outcomes between open reduction and internal fixation versus double reverse traction closed reduction and percutaneous internal fixation for tibial plateau fractures.Methods:A retrospective analysis was conducted of the data of 229 patients with tibial plateau fracture who had been admitted to Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University from January 2023 to December 2023. There were 155 males and 74 females with an age of (48.7±10.9) years. According to the surgical methods, the patients were divided into 2 groups. A conventional group of 87 cases were treated by open reduction and internal fixation while a minimally invasive group of 142 cases treated with double reverse traction closed reduction and percutaneous internal fixation. The 2 groups were compared in terms of hematological indexes [white blood cell count (WBC), neutrophil count (NEUT), lymphocyte count (LYM), monocyte count (Mono), platelet count (PLT), and albumin (ALB)] and composite inflammatory indexes [neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI)] before operation and on the first day after operation, intraoperative blood loss, operation time, fracture healing time, Hospital for Special Surgery (HSS) knee score and incidence of thrombosis.Results:There were no significant differences in baseline characteristics or treatment variables between the 2 groups, indicating comparability ( P > 0.05). All the 229 patients were followed up for (16.5±2.8) months. In each group, comparisons between preoperation and postoperation showed that LYM and ALB significantly decreased while WBC, NEUT, Mono, PLT, NLR, PLR, SII and SIRI significantly increased on the first day after operation ( P < 0.05). Preoperatively, there were no significant differences between the 2 groups in terms of hematological or composite inflammatory indexes ( P > 0.05). On the first day after operation, there was no significant difference in WBC, NEUT, LYM, ALB or NLR between the 2 groups ( P > 0.05), but Mono, PLT, PLR, SII and SIRI in the minimally invasive group were significantly lower than those in the conventional group ( P < 0.05). The intraoperative blood loss, operation time, fracture healing time, HSS knee score and incidence of thrombosis in the minimally invasive group were significantly better than those in the conventional group ( P < 0.05). Conclusion:In the treatment of tibial plateau fractures, compared with conventional open reduction and internal fixation, double reverse traction closed reduction and percutaneous internal fixation shows obvious advantages in reducing inflammatory indicators and leads to better surgical outcomes.

Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.

Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To compare postoperative inflammatory markers and surgical outcomes between open reduction and internal fixation versus double reverse traction closed reduction and percutaneous internal fixation for tibial plateau fractures.Methods:A retrospective analysis was conducted of the data of 229 patients with tibial plateau fracture who had been admitted to Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University from January 2023 to December 2023. There were 155 males and 74 females with an age of (48.7±10.9) years. According to the surgical methods, the patients were divided into 2 groups. A conventional group of 87 cases were treated by open reduction and internal fixation while a minimally invasive group of 142 cases treated with double reverse traction closed reduction and percutaneous internal fixation. The 2 groups were compared in terms of hematological indexes [white blood cell count (WBC), neutrophil count (NEUT), lymphocyte count (LYM), monocyte count (Mono), platelet count (PLT), and albumin (ALB)] and composite inflammatory indexes [neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI)] before operation and on the first day after operation, intraoperative blood loss, operation time, fracture healing time, Hospital for Special Surgery (HSS) knee score and incidence of thrombosis.Results:There were no significant differences in baseline characteristics or treatment variables between the 2 groups, indicating comparability ( P > 0.05). All the 229 patients were followed up for (16.5±2.8) months. In each group, comparisons between preoperation and postoperation showed that LYM and ALB significantly decreased while WBC, NEUT, Mono, PLT, NLR, PLR, SII and SIRI significantly increased on the first day after operation ( P < 0.05). Preoperatively, there were no significant differences between the 2 groups in terms of hematological or composite inflammatory indexes ( P > 0.05). On the first day after operation, there was no significant difference in WBC, NEUT, LYM, ALB or NLR between the 2 groups ( P > 0.05), but Mono, PLT, PLR, SII and SIRI in the minimally invasive group were significantly lower than those in the conventional group ( P < 0.05). The intraoperative blood loss, operation time, fracture healing time, HSS knee score and incidence of thrombosis in the minimally invasive group were significantly better than those in the conventional group ( P < 0.05). Conclusion:In the treatment of tibial plateau fractures, compared with conventional open reduction and internal fixation, double reverse traction closed reduction and percutaneous internal fixation shows obvious advantages in reducing inflammatory indicators and leads to better surgical outcomes.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective Through the study of different grades for Atractylodis macrocephalae Rhizoma decoction pieces,improve the quality evaluation method,and provide theoretical basis for the classification of Atractylodis macrocephalae Rhizoma.Methods According to the traditional classification,the Atractylodis macrocephalae Rhizoma decoction pieces was divided into three grades.By HPLC and UV method,the determination of atractylodes lactone Ⅰ,Ⅱ,Ⅲ and the content of total polysaccharide for 36 batches of different grades of Atractylodis macrocephalae Rhizoma decoction pieces.According to the 2020 edition of Chinese pharmacopoeia,the correlation between the appearance traits of different grades of Atractylodis macrocephalae Rhizoma decoction pieces and the internal quality control indexes was analyzed.Results According to the appearance characters,multiple quality control index of content determination,through the principal component analysis,cluster analysis and so forth.The quality of first-grade decoction pieces of Atractylodis macrocephalae Rhizoma is significantly better than the second-grade and third-grade decoction pieces(P<0.05),and there is no significant difference between second-grade and third-grade decoction pieces(P>0.05).As a result,the Atractylodis macrocephalae Rhizoma decoction pieces can be divided into two grades,different grades with the content of atractylodes lactone and total polysaccharide were positively correlated.Conclusion The classification of Atractylodis macrocephalae Rhizoma decoction pieces based on multiple quality control indexes combined with appearance characters can provide a scientific basis for the quality control and grade study of this decoction piece.

Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.