Objective: To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD). Methods: Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18. Results: Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05). Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Primary hepatocellular carcinoma(HCC)is a common malignant tumor in the world,and in China it is the fourth most common malignant tumor and the second cause of cancer mortality.In China,most HCC patients are already in the advanced stage when the clinical diagnosis of HCC is confirmed,and it is impossible to adopt a radical treatment for the patient.At present,transarterial chemoembolization(TACE)has become the mainstream therapeutic option for unresectable HCC,and hepatic arterial perfusion chemotherapy(HAIC),as a new therapeutic option,has attracted extensive attention.This article reviews the research progress in TACE combined with HAIC for the treatment of HCC,and obtains the following conclusions:TACE combined with HAIC has better efficacy than TACE along in patients with unresectable HCC of BCLC stage C,massive HCC,and portal venous invasion,but there is no significant difference in the therapeutic efficacy between TACE combined with HAIC and TACE alone for patients with HCC of BCLC stage A/B.It is expected that this review will provide effective recommendations for treating HCC patients in clinical practice,further standardize TACE treatment and later-stage HAIC treatment,and provide the basis for the design of relevant clinical studies.

Objective To systematically evaluate the accuracy of computer navigation technique in the positioning of bone tunnel location of anterior cruciate ligament reconstruction(ACLR) and its effect on post-operative functional recovery.Methods The controlled trials of computer navigation-assisted ACLR in the da-tabases of Cochrane Library,PubMed,Embase,CNKI,Wanfang and VIP Database were retrieved.The retriev-al time limit was from the establishment of the database to August 2023.According to the inclusion and exclu-sion criteria,the NoteExpress V3.0 software was used to screen the literatures,the Cochrane risk bias assess-ment tool was used to evaluate the quality of the included literatures,and the RevMan5.4 software was used for conducting the meta analysis.Results A total of 10 trials involving 705 patients were included,including 354 cases in the navigation group and 351 cases in the conventional group.The meta analysis results showed that compared with the conventional group,the location positioning of bone tunnel in the navigation group was significantly improved[in femoral side (MD=5.59,95％CI:1.21-9.97,P=0.01) and tibial side (MD=1.32,95％CI:0.20-2.43,P=0.02).However there were no statistically significant differences in the IKDC scores (MD=1.76,95％CI:-0.17 to 3.70,P=0.07),Lysholm scores (MD=0.49,95％CI:-0.16 to 1.14,P=0.14),Tegner scores (MD=-0.08,95％CI:-0.35 to 0.20,P=0.58),KT-1000 anterior shift dis-tance (MD=0.01,95％CI:-0.49 to 0.52,P=0.96),the positive rate of Lachman test (RD=-0.01,95％CI:-0.09 to 0.07,P=0.75) and the positive rate of axial shift test (RD=-0.09,95％CI:-0.22 to 0.04,P=0.20).Conclusion The computer navigation technology is conducive to elevate the accuracy of tibial and femoral tunnel positioning in ACLR,but could not improve the postoperative functional recovery of the pa-tients.

Objective To compare the effectiveness and safety of transparency cap-assisted endoscopic full-thickness resection(EFTR-C)and endoscopic submucosal excavation(ESE)in the treatment of ≤1.5 cm intracavity growth type gastric stromal tumor.Methods A retrospective analysis was performed on the medi-cal records of 63 patients with ≤1.5 cm intraluminal growth type gastric stromal tumor treated in this hospi-tal from June 2019 to September 2023.The patients were divided into the EFTR-C group(n=33)and ESE group(n=30)according to surgical methods.The general data,operation situation,postoperative situation and follow-up were compared between the two groups.Results There was no statistically significant differ-ence in the intraoperative pneumoperitoneum rate,purse string suture rate,monoblock resection rate,complete resection rate and complication occurrence rate between the two groups(P＞0.05).The operative time,inci-dence rate of intraoperative bleeding,number of titanium clips,postoperative fasting time,postoperative hospi-talization duration and operation costs had statistical difference between the two groups(P＜0.05).Postoper-ative wound healing was good in both groups without recurrence,metastasis and death.Conclusion EFTR-C for the treatment of ≤1.5 cm intracavity growth type gastric stromal tumor has the advantages of simple op-eration,short operation time,low costs and rapid recovery compared with ESE.

Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.

ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription （ZJYP） in Goto-Kakizaki （GK） rats with early-stage diabetic kidney disease （DKD）. MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding， with fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1 and urinary albumin/creatinine ratio （ACR） ≥ 30 mg·g^-1 used as model criteria. After successful modeling， DKD rats were randomly divided into five groups （n=10 in each group）： the model group， the western medicine group treated with dapagliflozin （1.0 mg·kg^-1·d^-1）， low-， medium-， and high-dose ZJYP groups （4.9， 9.9， 19.9 g·kg^-1·d^-1 by gavage）. Ten Wistar rats served as normal controls， with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR， FBG， body weight， and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect miRNA-27a， Wnt， and β-catenin mRNA and protein expression levels in renal tissues. ResultCompared with the results in the normal group， the FBG levels in DKD rats of the model group increased significantly at 0， 2， 4， 6， and 8 weeks of drug intervention （P<0.05）， and urinary ACR increased significantly at 0， 4， 8 weeks （P<0.05）. Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix， slight thickening of the basement membrane， and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a， Wnt， and β-catenin were significantly higher in the model group than in the normal group （P<0.05）. Renal Wnt and β-catenin protein levels were also significantly higher in the model group （P<0.05）. After drug intervention， the FBG levels in the low-， medium-， and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks （P<0.05）. The urinary ACR also showed a dose-dependent decrease in the low-， medium-， and high-dose ZJYP groups， but the differences were not statistically significant. There were no significant differences in liver function， renal function， renal index， or routine blood lipid test results among the low-， medium-， and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group， with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a， Wnt， and β-catenin were significantly lower in the high-dose ZJYP group （P<0.05）， and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group （P<0.05）. The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group， but the differences were not statistically significant. ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats， thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.

Objective To analyze the short- and mid-term outcomes of patients undergoing reconstruction of intervalvular fibrous body (IVFB) via double valve replacement (Commando procedure) or aortic valve replacement and mitral valve repair (Hemi-Commando procedure). Methods The patients who underwent Commando or Hemi-Commando procedure between September 2014 and September 2022 in Guangdong Provincial People’s Hospital were collected. The perioperative and follow-up data were reviewed and analyzed for the assessment of short- and mid-term outcomes. Results Eleven patients received Commando procedure (a Commando group), including 4 males and 7 females with a median age of 61 (33, 68) years; 7 patients received Hemi-Commando procedure (a Hemi-Commando group), including 5 males and 2 females with a median age of 50 (36, 58) years. Two patients died in the postoperative 30 days (1 patient in the Commando group and 2 patients in the Hemi-commando group). Low cardiac output syndrome complicated with multiple organ dysfunction syndrome was the main cause of death. Fifteen patients were discharged and followed up for 13 (6, 42) months, with a survival rate of 100%. The rates of free from recurrent endocarditis or re-operation were both 100%. Conclusion Commando and Hemi-Commando procedures are effective strategies for IVFB reconstruction, and can achieve excellent mid-term outcomes if patients survive from the frailest period of early postoperative stage.

Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.