1.Fresh Rehmanniae Radix regulates cholesterol metabolism disorder in mice fed with high-fat and high-cholesterol diet via FXR-mediated bile acid reabsorption.
Xin-Yu MENG ; Yan CHEN ; Li-Qin ZHAO ; Qing-Pu LIU ; Yong-Huan JIN ; Wei-Sheng FENG ; Xiao-Ke ZHENG
China Journal of Chinese Materia Medica 2025;50(6):1670-1679
This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals
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Male
;
Bile Acids and Salts/metabolism*
;
Mice, Inbred C57BL
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Mice
;
Diet, High-Fat/adverse effects*
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Cholesterol/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
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Hypercholesterolemia/genetics*
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Receptors, Cytoplasmic and Nuclear/genetics*
;
Rehmannia/chemistry*
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Liver/drug effects*
;
Humans
;
Cholesterol 7-alpha-Hydroxylase/genetics*
;
Plant Extracts
2.Clinical correlation study between bone metabolism level and knee osteoarthritis pain.
Yong-Qi SUN ; Ke-Chun GUO ; Ze-Zhong LIU ; Jin-Shuai DUAN ; Bing XU ; Guo-Gang LUO ; Xian-Liang LAI ; Xiao-Feng WANG
China Journal of Orthopaedics and Traumatology 2025;38(5):482-486
OBJECTIVE:
To investigate the variability of bone metabolism levels among different populations and its association with knee osteoarthritis (KOA) pain.
METHODS:
A total of 50 people (control group) who participated in physical examination from January 2023 to June 2023 were selected, including 26 males and 24 females, wtih a mean aged of (52.14±9.04) years old ranging 41 to 65 years old. The other 50 patients with knee osteoarthritis(case group) who attended the outpatient clinic of the Orthopedics and Traumatology Department in the same time period, including 19 males and 31 females, with a mean age of (53.60±7.76) years old ranging 40 to 65 years. The two groups of Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) and bone metabolism markers, such as 25-hydroxy-cholecalciferol[25(OH)D], β-isomerized typeⅠcollagen C-telopeptide breakdown products (β-CTX), total typeⅠprocollagen N-terminal propeptide (t-PINP), osteocalcin (OC), parathormone (PTH) levels were compared. Pearson correlation analysis was used to compare the correlation between two groups of bone metabolism related markers and WOMAC.
RESULTS:
The WOMAC score of the case group (39.90±2.34) was higher than that of the control group (3.60±0.57), with significant difference (P<0.05). There was no significant difference between the two groups of 25 (OH)D, β-CTX and PTH (P>0.05). The t-PINP and OC of the case group were (62.90±52.40) and (19.88±10.15) ng·ml-1, respectively, and those of the control group were (38.86±10.82) and (14.90±3.62) ng·ml-1, respectively;the t-PINP and OC of the case group were higher than those of the control group, with significant difference (P<0.05). Pearson correlation analysis showed that t-PINP was positively correlated with WOMAC pain score in the case group (r2=0.045, P<0.01).
CONCLUSION
Bone metabolism levels in the serum of patients with knee osteoarthritis are different from those of healthy people, and the difference between OC and t-PINP is the most obvious, and the concentration of t-PINP levels is positively correlated with pain symptoms in patients with KOA. However, the specific mechanism of correlation between the bone metabolism levels of patients with KOA and their pain symptoms needs to be further elucidated by basic experimental research as well as by enlarging the samples.
Humans
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Female
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Male
;
Middle Aged
;
Osteoarthritis, Knee/metabolism*
;
Aged
;
Adult
;
Bone and Bones/metabolism*
;
Pain/etiology*
;
Biomarkers/metabolism*
3.Observation on the therapeutic effect of a modified Devine procedure with subcutaneous sliding fixation method for concealed penis.
Mohammed Abdulkarem AL-QAISI ; Hai-Fu TIAN ; Jia-Jin FENG ; Ke-Ming CHEN ; Jin ZHANG ; Yun-Shang TUO ; Xue-Hao WANG ; Bin-Cheng HUANG ; Muhammad Arslan Ul HASSAN ; Rui HE ; Guang-Yong LI
Asian Journal of Andrology 2025;27(4):470-474
To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans
;
Male
;
Penis/abnormalities*
;
Retrospective Studies
;
Urologic Surgical Procedures, Male/methods*
;
Treatment Outcome
;
Child
;
Plastic Surgery Procedures/methods*
4.Vonoprazan for ulcers associated with endoscopic submucosal dissection:a rapid health technology assessment
Wei WANG ; Yijun KE ; Chang CHENG ; Chongwen FANG ; Lisheng PAN ; Yong JIN ; Yanping ZHANG
Chinese Journal of Pharmacoepidemiology 2025;34(3):306-313
Objective To evaluate the efficacy,safety and economy of vonoprazan in the treatment of post-endoscopic submucosal dissection(ESD)ulcer by rapid health technology assessment method,and to provide reference for clinical treatment decision.Methods PubMed,Cochrane Library,Embase,ScienceDirect,CNKI,WanFang Data databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of vonoprazan in the treatment of post-ESD ulcer from inception to July 31,2024.Two researchers independently screened literature,extracted data,and comprehensively analyzed the results of the included literature on the basis of literature quality evaluation.Results A total of 8 studies were included,all were systematic reviews/Meta-analysis.In terms of effectiveness,compared with proton pump inhibitors(PPI),vonoprazan significantly increased the overall ulcer healing rate after ESD and more rapid reduction of ulcer area(P<0.05).The results of subgroup analysis showed that there was no significant difference in ulcer healing rate between vonoprazan and PPI treatment at 4 or 8 weeks after ESD(P>0.05).Vonoprazan significantly increased the rate of postoperative ulcer reduction in H.pylori positive patients compared with PPI(P<0.05).In terms of safety,compared with PPI,vonoprazan reduced the incidence of overall adverse events rate(P<0.05).The difference in the incidence of delayed bleeding and ulcer perforation between vonoprazan and PPIs showed no statistically significant difference.(P>0.05).Conclusion Vonoprazan demonstrated favorable efficacy and safety in the treatment of ESD ulcers,and further economic studies are warranted.
5.Patterns of lymph node metastasis and prognosis in locally-advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy
Peng JIN ; Bin KE ; Yong LIU ; Hongmin LIU ; Rupeng ZHANG ; Han LIANG
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1006-1014
Objective:To explore the pattern of lymph node metastasis and prognosis in locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy (NICT).Methods:This retrospective study included pathologically confirmed gastric adenocarcinoma (cT3-4aN+) patients who underwent radical resection after ≥2 cycles of PD-1 inhibitor-based chemotherapy with complete postoperative pathology. Exclusions: distant/other metastases, non-R0 resection, Her-2+ with targeted therapy, microsatellite instability, or esophagogastric junction cancer invading >1 cm into lower esophagus. From January 2020 to December 2024, a total of 343 consecutive gastric cancer patients who received NICT treatment were admitted to Tianjin Medical University Cancer Institute and Hospital. According to the above criteria, 324 cases were included in the lymph node metastasis analysis, and 302 cases were included in the survival analysis. The median age of all patients was 58 years, with 245 males (75.6%) and a median body mass index (BMI) of 22.9 kg/m2. There were 170 cases (52.5%) at T3 stage and 154 cases (47.5%) at T4a stage; the median number of cycles of neoadjuvant immunotherapy combined with chemotherapy was 3 cycles. The primary outcome measure was the positive lymph node metastasis rate (number of metastatic cases in the group / total number of dissected cases in the group×100%). A positive lymph node metastasis rate >10% was defined as high metastasis, and <5% as low metastasis. The secondary outcome measures were high-risk factors for lymph node metastasis and influencing factors related to patient prognosis. Lymph node grouping was performed according to the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines. The positive lymph node metastasis rate was statistically analyzed by stratification based on surgical methods (total gastrectomy, proximal gastrectomy, distal gastrectomy). Multivariate analysis of risk factors for lymph node metastasis were performed with logistic regression analysis, and survival analysis were performed with the Kaplan-Meier method and Cox regression model.Results:The postoperative pathological complete response rate (pCR) of all patients was 21.0% (68/324), and the overall positive lymph node metastasis rate was 48.8% (158/324). A total of 150 patients underwent total gastrectomy, 42 underwent proximal gastrectomy, and 132 underwent distal gastrectomy.In the total gastrectomy group: the high metastasis subgroups were No.1 (19.3%, 29 cases), No.2 (14.7%, 22 cases), No.3 (28.0%, 42 cases), No.7 (12.7%, 19 cases), No.8a (16.0%, 24 cases), and No.9 (17.3%, 26 cases); the low metastasis subgroups were No.5 (4.7%, 7 cases), No.10 (3.3%, 5 cases), No.11d (1.3%, 2 cases), and No.12a (4.0%, 6 cases).In the proximal gastrectomy group: the high metastasis subgroups were No.3 (14.3%, 6 cases), No.7 (23.8%, 10 cases), and No.11p (11.9%, 5 cases); the low metastasis subgroups were No.4d (2.4%, 1 case) and No.10 (2.4%, 1 case).In the distal gastrectomy group: the high metastasis subgroups were No.3 (25.8%, 34 cases), No.6 (26.5%, 35 cases), No.7 (11.4%, 15 cases), and No.11p (11.4%, 15 cases); the low metastasis subgroups were No.4sb (3.8%, 5 cases) and No.12a (4.5%, 6 cases).Results of multivariate analysis showed that TRG grade (HR: 5.938, 95%CI: 3.028-11.646, P<0.001) was an independent factor affecting lymph node metastasis in patients with locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy. The median follow-up time was 26.0 (6.0-54.3) months, and the 3-year overall survival (OS) of all patients was 78.1%. Results of multivariate Cox analysis showed that ypT (HR=1.744, 95%CI: 1.300-2.338, P<0.001), ypN (HR=1.998, 95%CI: 1.503-2.655, P<0.001), and postoperative complications (HR=1.913, 95%CI: 1.111-3.294, P=0.019) were independent factors affecting the overall survival of patients with locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy. Conclusion:NICT significantly changes the pattern of lymph node metastasis in LAGC. ypT and ypN stages are core indicators for survival prognosis. The necessity of dissection for lymph node groups with a metastasis rate <5% needs to be carefully evaluated.
6.Vonoprazan for ulcers associated with endoscopic submucosal dissection:a rapid health technology assessment
Wei WANG ; Yijun KE ; Chang CHENG ; Chongwen FANG ; Lisheng PAN ; Yong JIN ; Yanping ZHANG
Chinese Journal of Pharmacoepidemiology 2025;34(3):306-313
Objective To evaluate the efficacy,safety and economy of vonoprazan in the treatment of post-endoscopic submucosal dissection(ESD)ulcer by rapid health technology assessment method,and to provide reference for clinical treatment decision.Methods PubMed,Cochrane Library,Embase,ScienceDirect,CNKI,WanFang Data databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of vonoprazan in the treatment of post-ESD ulcer from inception to July 31,2024.Two researchers independently screened literature,extracted data,and comprehensively analyzed the results of the included literature on the basis of literature quality evaluation.Results A total of 8 studies were included,all were systematic reviews/Meta-analysis.In terms of effectiveness,compared with proton pump inhibitors(PPI),vonoprazan significantly increased the overall ulcer healing rate after ESD and more rapid reduction of ulcer area(P<0.05).The results of subgroup analysis showed that there was no significant difference in ulcer healing rate between vonoprazan and PPI treatment at 4 or 8 weeks after ESD(P>0.05).Vonoprazan significantly increased the rate of postoperative ulcer reduction in H.pylori positive patients compared with PPI(P<0.05).In terms of safety,compared with PPI,vonoprazan reduced the incidence of overall adverse events rate(P<0.05).The difference in the incidence of delayed bleeding and ulcer perforation between vonoprazan and PPIs showed no statistically significant difference.(P>0.05).Conclusion Vonoprazan demonstrated favorable efficacy and safety in the treatment of ESD ulcers,and further economic studies are warranted.
7.Patterns of lymph node metastasis and prognosis in locally-advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy
Peng JIN ; Bin KE ; Yong LIU ; Hongmin LIU ; Rupeng ZHANG ; Han LIANG
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1006-1014
Objective:To explore the pattern of lymph node metastasis and prognosis in locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy (NICT).Methods:This retrospective study included pathologically confirmed gastric adenocarcinoma (cT3-4aN+) patients who underwent radical resection after ≥2 cycles of PD-1 inhibitor-based chemotherapy with complete postoperative pathology. Exclusions: distant/other metastases, non-R0 resection, Her-2+ with targeted therapy, microsatellite instability, or esophagogastric junction cancer invading >1 cm into lower esophagus. From January 2020 to December 2024, a total of 343 consecutive gastric cancer patients who received NICT treatment were admitted to Tianjin Medical University Cancer Institute and Hospital. According to the above criteria, 324 cases were included in the lymph node metastasis analysis, and 302 cases were included in the survival analysis. The median age of all patients was 58 years, with 245 males (75.6%) and a median body mass index (BMI) of 22.9 kg/m2. There were 170 cases (52.5%) at T3 stage and 154 cases (47.5%) at T4a stage; the median number of cycles of neoadjuvant immunotherapy combined with chemotherapy was 3 cycles. The primary outcome measure was the positive lymph node metastasis rate (number of metastatic cases in the group / total number of dissected cases in the group×100%). A positive lymph node metastasis rate >10% was defined as high metastasis, and <5% as low metastasis. The secondary outcome measures were high-risk factors for lymph node metastasis and influencing factors related to patient prognosis. Lymph node grouping was performed according to the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines. The positive lymph node metastasis rate was statistically analyzed by stratification based on surgical methods (total gastrectomy, proximal gastrectomy, distal gastrectomy). Multivariate analysis of risk factors for lymph node metastasis were performed with logistic regression analysis, and survival analysis were performed with the Kaplan-Meier method and Cox regression model.Results:The postoperative pathological complete response rate (pCR) of all patients was 21.0% (68/324), and the overall positive lymph node metastasis rate was 48.8% (158/324). A total of 150 patients underwent total gastrectomy, 42 underwent proximal gastrectomy, and 132 underwent distal gastrectomy.In the total gastrectomy group: the high metastasis subgroups were No.1 (19.3%, 29 cases), No.2 (14.7%, 22 cases), No.3 (28.0%, 42 cases), No.7 (12.7%, 19 cases), No.8a (16.0%, 24 cases), and No.9 (17.3%, 26 cases); the low metastasis subgroups were No.5 (4.7%, 7 cases), No.10 (3.3%, 5 cases), No.11d (1.3%, 2 cases), and No.12a (4.0%, 6 cases).In the proximal gastrectomy group: the high metastasis subgroups were No.3 (14.3%, 6 cases), No.7 (23.8%, 10 cases), and No.11p (11.9%, 5 cases); the low metastasis subgroups were No.4d (2.4%, 1 case) and No.10 (2.4%, 1 case).In the distal gastrectomy group: the high metastasis subgroups were No.3 (25.8%, 34 cases), No.6 (26.5%, 35 cases), No.7 (11.4%, 15 cases), and No.11p (11.4%, 15 cases); the low metastasis subgroups were No.4sb (3.8%, 5 cases) and No.12a (4.5%, 6 cases).Results of multivariate analysis showed that TRG grade (HR: 5.938, 95%CI: 3.028-11.646, P<0.001) was an independent factor affecting lymph node metastasis in patients with locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy. The median follow-up time was 26.0 (6.0-54.3) months, and the 3-year overall survival (OS) of all patients was 78.1%. Results of multivariate Cox analysis showed that ypT (HR=1.744, 95%CI: 1.300-2.338, P<0.001), ypN (HR=1.998, 95%CI: 1.503-2.655, P<0.001), and postoperative complications (HR=1.913, 95%CI: 1.111-3.294, P=0.019) were independent factors affecting the overall survival of patients with locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy. Conclusion:NICT significantly changes the pattern of lymph node metastasis in LAGC. ypT and ypN stages are core indicators for survival prognosis. The necessity of dissection for lymph node groups with a metastasis rate <5% needs to be carefully evaluated.
8.Rapid health technology assessment of the efficacy,safety and cost-effectiveness of vericiguat in the treatment of heart failure
Yijun KE ; Wei WANG ; Can HUANG ; Yong JIN ; Lamei QI
China Pharmacy 2024;35(15):1818-1824
OBJECTIVE To evaluate the efficacy, safety and cost-effectiveness of vericiguat in the treatment of heart failure (HF) by rapid health technology evaluation method, and provide reference for the selection and decision-making of clinical treatment plans. METHODS Chinese and foreign databases such as CNKI, PubMed and related health technology evaluation websites were searched by computer. Relevant researchers independently screened literature, extracted data, and comprehensively analyzed the results of the included literature based on literature quality evaluation. RESULTS A total of 17 pieces of literature were included, involving 12 systematic reviews/meta-analyses and 5 pharmacoeconomic studies. The effectiveness analysis showed: for HF patients, compared with placebo, vericiguat (10 mg/d) significantly improved the EuroQol five dimensions questionnaire (EQ-5D) index and decreased the rate of hospitalization due to HF (P<0.05). For heart failure with reduced ejection fraction (HFrEF) patients, vericiguat reduced the incidence of hospitalization due to HF compared with sodium-glucose cotransporter 2 inhibitor (SGLT2i)(P<0.05); compared with angiotensin-converting enzyme inhibitor, vericiguat significantly reduced the occurrence risk of composite endpoints of cardiovascular death or hospitalization due to HF(P<0.05). For HFrEF patients with chronic kidney disease, vericiguat had a tendency to reduce the occurrence risk of composite endpoints of cardiovascular death or hospitalization due to HF compared with neurohormone inhibitors. Safety analysis showed: vericiguat did not increase drug-related adverse reactions compared to placebo (P>0.05). Economic analysis showed: domestic studies indicated that vericiguat had a higher incremental cost-effectiveness ratio. CONCLUSIONS Vericiguat has good safety and efficacy in the treatment of HF but does not possess an economic advantage in the Chinese population.
9.Design,numerical simulation and experimental study of novel oxygenator
Ming-Hao YUE ; Shi-Yao ZHANG ; Ji-Nian LI ; Hui-Chao LIU ; Zi-Hua SU ; Ya-Wei WANG ; Zeng-Sheng CHEN ; Shi-Hang LIN ; Jin-Yu LI ; Ya-Ke CHENG ; Yong-Fei HU ; Cun-Ding JIA ; Ming-Zhou XU
Chinese Medical Equipment Journal 2024;45(3):23-28
Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]
10.Clinical implications of Naples prognostic scores in patients with resectable Siewert type II-III adenocarcinoma of the esophagogastric junction
Peng JIN ; Gang MA ; Yong LIU ; Bin KE ; Hongmin LIU ; Han LIANG ; Rupeng ZHANG
Chinese Journal of Gastrointestinal Surgery 2024;27(1):54-62
Objective:To evaluate the clinical value of preoperative Naples prognostic scores (NPS) in patients with resectable Siewert type II-III esophagogastric junction adenocarcinoma (AEG).Methods:In this retrospective observational study we collected and analyzed relevant data of patients with Siewert Type II-III AEG treated in the Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital from January 2014 to December 2018. NPS were calculated using preoperative albumin concentration, total cholesterol concentration, neutrophil/lymphocyte ratio, and lymphocyte/monocyte ratio and used to allocate patients into three groups: NTS-0 (0 points), NTS-1 (1-2 points) and NTS-2 (3-4 points). Kaplan–Meier was used to calculate disease-free survival (DFS) and overall survival (OS) in each NPS group and the log-rank test to compare these groups. Univariate and multivariate survival analyes were performed using the Cox regression model. Time-dependent receiver operating characteristic curves were constructed to compare the relationships between four commonly used tools for evaluating inflammatory responses and nutritional status:NPS, systemic inflammatory response scores, nutrient control status (CONUT), and prognostic nutrition index (PNI).Results:The study cohort comprised 221 patients with AEG of median age 63.0 (36.0–87.0) years. There were 190 men (86.0%) and 31 women (14.0%). As to pTNM stage, 47 patients (21.3%) had Stage I disease, 68 (30.8%) Stage II, and 106 (48.0%) Stage III. One hundred and forty-seven patients (66.5%) had Siewert Type II disease and 74 (33.5%) Siewert type III. There were 45 patients (20.4%) in the NPS-0, 142 (64.2%) in the NPS-1 and 34 (15.4%) in the NPS-2 groups. Higher NPS scores were significantly associated with older patients (χ2=5.056, P=0.027) and higher TNM stages ( H=5.204, P<0.001). The median follow-up was 39 (6-105) months; 16 patients (7.2%) were lost to follow-up. The median OS in the NPS-0, NPS-1, and NPS-2 groups were 78.4, 63.1, and 37.0 months, respectively; these differences are statistically significant ( P=0.021). Univariate and multivariate Cox regression analysis identified the following as independently and significantly associated with OS in patients with Siewert Type II-III: TNM stage (Stage II: HR=2.182, 95%CI: 1.227-3.878, P=0.008; Stage III: HR=3.534, 95%CI: 1.380-6.654, P<0.001), tumor differentiation (G3: HR=1.995, 95%CI: 1.141-3.488, P=0.015), vascular invasion (HR=2.172, 95%CI: 1.403-3.363, P<0.001), adjuvant chemotherapy (HR=0.326, 95%CI: 0.200-0.531, P<0.001), NPS (NPS-1: HR=2.331, 95%CI: 1.371-3.964, P=0.002; NPS-2: HR=2.494, 95%CI: 1.165-5.341, P=0.019), SIS group (NPS-1: HR=2.170, 95%CI: 1.244-3.784, P=0.006; NPS-2: HR=2.291, 95%CI: 1.052–4.986, P=0.037), and CONUT (HR=1.597, 95% CI: 1.187-2.149, P=0.038). The median DFS in the NPS-0, NPS-1, and NPS-2 groups was 68.6, 52.5, and 28.3 months, respectively; these differences are statistically significant ( P=0.009). Univariate and multivariate Cox regression analysis identified the following as independently and significantly associated with DFS in patients with Siewert Type II-III AEG: TNM stage (StageⅡ: HR=2.789, 95%CI:1.210-6.428, P=0.016; Stage III: HR=10.721, 95%CI:4.709-24.411, P<0.001), adjuvant chemotherapy (HR=0.640, 95% CI: 0.432-0.946, P=0.025), and NPS (NPS-1: HR=1.703, 95%CI: 1.043-2.782, P=0.033; NPS-2: HR=3.124, 95%CI:1.722-5.666, P<0.001). Time-dependent receiver operating characteristic curves showed that NPS was more accurate in predicting OS and DFS in patients with Siewert Type II-III AEG than were systemic inflammatory response scores, CONUT, or PNI scores. Conclusion:NPS is associated with age and TNM stage, is an independent prognostic factor in patients who have undergone resection of Siewert type II-III AEG, and is better than SIS, CONUT, or PNI in predicting survival.

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