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 ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

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 ; Female ; Male ; Middle Aged ; Osteoarthritis, Knee/metabolism* ; Aged ; Adult ; Bone and Bones/metabolism* ; Pain/etiology* ; Biomarkers/metabolism*

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*

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.

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.

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.

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.

Combined radiation and burn injury (CRBI) is a severe syndrome, which is induced by the simultaneous or successive radiation and burn; but no appropriate clinical therapies are available. Loong oil (LO) is a traditional Chinese medicine oil composed of the oil extracts of cuttlebone, safflower, walnut oil, and rapeseed oil, which has been demonstrated to own anti-radiation and tissue healing functions. In this study, glyceryl monostearate (GMO) was used for the preparation of lyotropic liquid crystals that loaded LO to obtain Loong oil-lyotropic liquid crystals (LOL) for the treatment of skin CRBI. The hexagonal phase structure of LOL was proved by small X-ray scattering (SAXS) analysis with an approximate 7:9:11 ratio of peaks and under the polarizing microscope with the birefringence phenomenon. LOL had a high LO loading capacity (4%) and good bio-adhesive force, favoring skin administration. Animal experiments were approved by the Ethics Committee of the Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations (approval number: IACUC-DWZX-2022-834). Compared to triethanolamine creams, LOL had higher skin permeability with total skin penetration within 1 h, benefiting the treatment of deep CRBI. A deep II degree burn CRBI mouse model was established after whole-body irradiation with 5 Gy ⁶⁰Co γ-ray and the next 6-second 100 ℃ burn injury. LOL promoted LO skin penetration, improved epithermal cell proliferation and the formation of hair follicles, accelerated wound healing, and inhibited scarring, which benefitted the therapy of CRBI. In this study, LO application fields are expanded and LO is a promising medication for the treatment of CRBI.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the value of electrocardiogra(ECG)P-wave parameters com-bined with serum adiponectin and visfatin(VF)in predicting recurrence of atrial fibrillation(AF)after radiofrequency ablation.Methods A total of 120 AF patients(AF group)admitted to our hospital from March 2021 to March 2023 were enrolled,and divided into a recurrence group(39 cases)and a non-recurrence group(81 cases)according to the postoperative condition.Another 120 healthy individuals who took physical examination in the same period were enrolled and served as control group.All subjects underwent ECG.ELISA was used to detect adiponectin and VF levels.Logistic regression analysis was used to identify the influencing factors of postoperative recur-rence in AF patients.ROC curve was plotted to analyze the predictive value of P-wave parameters combined with serum adiponectin and VF for postoperative recurrence in AF patients.The P-wave parameters included P-wave duration(PWD),maximum PWD(Pmax),minimum PWD,and P-wave dispersion(Pd).Results PWD,Pmax and Pd were significantly decreased in AF patients after operation(P＜0.01).Serum adiponectin level was obviously lower and that of VF was nota-bly higher in the AF group than the control group(6.15±1.58 μg/L vs 11.43±2.26 μg/L,12.05±2.30 μg/L vs 6.23±1.02 μg/L,P＜0.01).The recurrence group had remarkably higher preopera-tive PWD,Pmax and Pd,and lower adiponectin and higher VF levels than the non-recurrence group(P＜0.01).Multivariate logistic regression analysis showed that PWD,Pmax,Pd,and VF were risk factors,and adiponectin was a protective factor for postoperative recurrence in AF pa-tients(P＜0.05,P＜0.01).ROC curve analysis indicated that PWD,Pmax,Pd,adiponectin and VF combined together to detect postoperative recurrence in AF patients had an AUC value of 0.972,which was higher than that of above indicators alone(Z=2.574,Z=2.567,Z=2.543,Z=2.554,Z=2.586,P＜0.05).Conclusion ECG P-wave parameters as well as elevated serum VF and re-duced serum adiponectin are influencing factors for postoperative recurrence in AF patients,and their combined detection may promote the predictive value for postoperative recurrence in them.