OBJECTIVE To analyze the correlation of the peak blood concentration （cmax） of compound sulfamethoxazole （TMP/SMZ） and its metabolite N-acetyl sulfamethoxazole （NSMZ） with clinical efficacy and adverse reactions in critically ill patients. METHODS The data of critically ill patients treated with TMP/SMZ in various ICU of Hainan General Hospital from December 2023 to January 2025 were retrospectively collected. The patients were divided into success group and failure group based on the treatment outcome. Simple linear regression and Spearman correlation analysis were used to analyze the correlation of TMP cmax， SMZ cmax， and NSMZ cmax with clinical efficacy and adverse reactions. The receiver operating characteristic curve （ROC） was used to determine the cutoff values of cmax for predicting the occurrence of adverse reactions. RESULTS Among critically ill patients with an acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） ≥15 points 24 h of check-in at ICU， SMZ cmax of success group was significantly higher than failure group （P＜0.05）. The daily total dose of TMP/SMZ was positively correlated with TMP cmax and SMZ cmax（ P＜0.05）. TMP cmax was significantly correlated with hepatotoxicity and nephrotoxicity， SMZ cmax with hepatotoxicity， and NSMZ cmax with nephrotoxicity （P＜0.05）. The cutoff values of TMP cmax for predicting nephrotoxicity and hepatotoxicity were 7.25 μg/mL and 6.63 μg/mL， respectively. The cutoff value of SMZ cmax for predicting hepatotoxicity was 138.00 μg/mL， and that of NSMZ cmax for predicting nephrotoxicity was 60.76 μg/mL. CONCLUSIONS Among critically ill patients with an APACHE-Ⅱ ≥15 points 24 h of check-in at ICU， SMZ cmax is associated with treatment success. Hepatotoxicity risk significantly increases when TMP cmax ≥6.63 μg/mL or SMZ cmax ≥138.00 μg/mL； nephrotoxicity risk significantly increases when TMP cmax ≥7.25 μg/mL or NSMZ cmax ≥60.76 μg/mL.

Objective To investigate the application of Rotarex mechanical thrombectomy system in lower extremity arterial thrombosis and to evaluate its clinical efficacy.Methods The clinical data of 61 patients(71 limbs,35 cases in acute phase,21 cases in subacute phase and 5 cases in chronic phase)with lower extremity arterial thrombosis treated with Rotarex were analyzed retro-spectively.Distal protective device was used in patients with poor distal artery outflow.High pressure saline was used during the pro-cedure and stent was used in patients with flow-limiting dissection.Catheter aspiration was performed in patients with distal artery embo-lization.Anticoagulant therapy was used in patients with thromboembolism and dual antiplatelet therapy was used in patients with in-situ thrombosis.Postoperative follow-up was performed with color Doppler ultrasound or computed tomography angiography(CTA)at 1 month,3 months and 6 months.Results Fifty-nine cases were treated with 6F Rotarex catheters and 2 cases were treated with 8F Rotarex catheters.Distal protective device was used in 10 cases,balloon dilation was performed in 49 cases and stent was used in 5 cases.Catheter aspiration was performed in 10 cases.Vessel rupture occurred in 4 cases,among whom 3 cases were successfully treated with the method of balloon compression and 1 case was treated with covered stent.Severe adverse events occurred in 4 cases and perioperative toe amputation was performed in 7 cases.Follow-up time was 3 to 6 months(mean 4.9 months).Lower extremity ischemic event occurred in 1 case at 6th month follow-up and was treated with stent.No other lower extremity ischemic events occurred in the course of follow-up.Conclusion For the treatment of lower extremity arterial thrombosis,Rotarex mechanical thrombectomy sys-tem has the advantages of minimally invasion,rapid and high efficiency.Combined with the therapy of catheter aspiration and stent place-ment,vascular patency can be further maintained and the lower extremity ischemic symptoms can be quickly relieved.

Angiogenesis is a key process in the development and progression of hepatocellular carcinoma(HCC)and can provide essential material conditions for the proliferation,invasion,and metastasis of HCC cells.Inhibition of angiogenesis has become a research hotspot in the field of HCC therapy.Traditional Chinese medicine has become a potential drug for HCC therapy due to its characteristics of multiple targets and pathways,enhancing efficacy and reducing toxicity,improving tumor prognosis,and prolonging survival time.Modern studies have confirmed that traditional Chinese medicine can inhibit tumor angiogenesis by inhibiting the expression of angiogenic factors,upregulating the levels of anti-angiogenic factors,inhibiting endothelial cell proliferation,reducing the microvascular density of HCC tissue,and regulating related signaling pathways,and therefore,traditional Chinese medicine has unique advantages in the treatment of HCC.By summarizing related articles in China and globally in recent years,this article analyzes the mechanism of action of traditional Chinese medicine on inhibiting HCC angiogenesis,in order to provide certain theoretical basis and reference for the optimization of HCC treatment strategies in clinical practice.

Objective To investigate the effect of electroacupuncture preconditioning on microglia polarization in rats after cerebral ischemia reperfusion(IR)injury and explore the role of tyrosine kinase 2(J AK2)/signal transducer and activator of transcription 3(STAT3)pathway in the process.Methods Forty-five clean-grade healthy male Sprague-Dawley rats were randomly and equally divided into sham operation group,IR group and electroacupuncture preconditioning group.Rat model of IR injury was induced with thread occlusion of the internal carotid artery.Before modeling,electroacupuncture preconditioning was applied to Baihui acupoint for 5 consec-utive days in the preconditioning group,and exposure of the cervical blood vessels were inflicted in the sham-operation group.At 24 h after reperfusion,the severity of neurological deficit was observed by modified neurological deficit score(mNSS),and the cerebral infarct volume was observed by TTC staining.Western blotting was used to detect the protein levels of classical acti-vated type(M1)marker inducible nitric oxide synthase(iNOS),alternative activated type(M2)marker arginase 1(Arg-1),JAK2 and p-JAK2,and STAT3 and p-STAT3,and q-PCR was applied to detect the mRNA expression of iNOS and Arg-1.The expression of TNF-α and IL-10 was measured by ELISA.Results Compared with the sham operation group,the mNSS,infarct vol-ume,protein levels of p-JAK2/JAK2,p-STAT3/STAT3,protein and mRNA levels of iNOS and Arg-1,and expression of TNF-α and IL-10 were significantly increased in the IR and electroacu-puncture preconditioning groups(P＜0.01).The preconditioning group had obviously lower mNSS,smaller infarct volume,decreased protein levels of p-JAK2/JAK2,p-STAT3/STAT3,re-duced protein and mRNA levels of iNOS,and declined TNF-α expression,but elevated expression of Arg-1 at protein(2.0±0.2 vs 1.5±0.1)and mRNA(4.2±0.8 vs 3.1±0.3)levels and increased IL-10 expression(49.1±7.1 pg/mg vs 27.9±5.9 pg/mg)when compared with the IR group(P＜0.01).Conclusion Electroacupuncture preconditioning can promote the polarization of microglia to M2 and inhibit the polarization of microglia to M1 after cerebral IR injury,which may be relat-ed to the inhibition of JAK2/STAT3 pathway.

Objective:To discuss the method of modified balloon-occluded retrograde transvenous obliteration (M-BRTO) combined with antegrade transvenous obliteration (ATO) using tissue adhesive and (or) coils in the treatment of portal hypertension with spontaneous portosystemic shunt (SPSS), and to evaluate its clinical efficacy.Methods:From February 2018 to October 2022,clinical data of patients with portal hypertension with SPSS treatment in Henan Anyang District Hospital were retrospectively analyzed. A total of 21 patients were enrolled. Under the blood flow limit of SPSS outflow tract, ATO was firstly performed, then followed by M-BRTO. The ATO route could be performed from percutaneous transhepatic portal vein, percutaneous transumbilical vein or transjugular intrahepatic portal vein shunt (TIPS) approach and the M-BRTO route could be performed from femoral vein (FV), jugular vein (JV) or anterior cubical vein (ACV). The operation of M-BRTO+ATO was performed under local anesthesia and was suitable for patients with isolated gastric varicose bleeding, hepatic encephalopathy or cardiac insufficiency. TIPS combination with M-BRTO+ATO was performed under general anesthesia and was suitable for patients with gastrointestinal hemorrhage complicated with severe gastrorenal or splenorenal shunt, or with portal thrombosis. Abdominal plain CT scan was performed 1 week later to show the deposition of embolic agent. Abdominal color ultrasound was done 1 month later, contrast-enhanced CT scan was performed 3 months and 6 months later, and then color ultrasound or contrast-enhanced CT was performed every 6 months to show the portal vein blood flow or the patency of TIPS stent. Hepatic artery chemoembolization was performed 1 month later for patients with liver cancer.Results:A total of 23 times of operation were performed in 21 patients, including 1 case with 3 times of operation. The approach of percutaneous transhepatic route was used in 11 cases (7 cases combined with FV, 3 cases combined with JV and 1 case combined with ACV), the approach of TIPS route combination with FV was used in 9 cases, paraumbilical vein combination with FV was used in 2 cases and paraumbilical vein combination with ACV was used in 1 case. Ectopic embolization occurred in 3 cases (1 case to the spleen vein, 2 cases to the liver). Perioperative fever occurred in 5 cases, bleeding of hepatic puncture tract occurred in 1 case, and death happened in 2 cases (1 case of acute liver failure induced by bile duct stone, 1 case of acute heart failure combined with acute gastrointestinal massive hemorrhage). During the follow-up, 4 cases died (3 cases of liver cancer and 1 case of infection). The remaining 15 patients were followed up for 2 to 47 (22±13) months and there was no recurrence of hepatic encephalopathy and gastrointestinal hemorrhage during follow-up.Conclusions:The operation of M-BRTO+ATO using tissue adhesive or combining with coils as embolic agent can quickly obliterate outflow tract of SPSS and completely block the whole tract of SPSS, so it is a fast, safety and effective method for the treatment of PH with SPSS.

With the development of population aging, the incidence of lower limb artery ischemic diseases is gradually increasing. Although various treatments such as medication and endovascular surgery are currently available, patients with compromised microcirculation in the distal limbs and poor outflow pathways often do not achieve satisfactory results. Additionally, these treatments can be costly, and long-term patency rates are not ideal. The amendment in situ autologous great saphenous vein arterialization surgery utilizes the patient′s great saphenous vein to provide arterial blood in a retrograde manner and re-establishes blood supply to the tissues through the venous microcirculation system in the distal foot. This approach can achieve good limb salvage results and long-term patency. Therefore, this article aims to elaborate on the methods and value of amendment in situ autologous great saphenous vein arterialization surgery.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

AIM: To establish a ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determination the plasma concentration of clozapine and compare the bioequivalence of a generic clozapine tablet with Clozaril

Objective:To investigate the short-term efficacy of left-sided three-port total laparoscopic distal gastrectomy (TPTLDG).Methods:The prospective randomized controlled study was conducted. The 68 patients undergoing laparoscopic distal gastrectomy in the First Affiliated Hospital of Air Force Medical University from March 2022 to March 2023 were collected. All patients were randomly assigned to the TPTLDG group with a double number, and to the five-port laparoscopic distal gastrectomy (FPLDG) group with a single number, respectively. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of perioperative condition; (3) comparison of complications during postoperative 30 days; (4) comparison of pathological examination. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or continuous correction chi-square test. Comparison of ordinal data was analyzed using the non‐parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 59 patients of gastric cancer were selected for eligibility. There were 40 males and 19 females, aged 59.00(52.00, 67.00)years. The gender (male, female), age, body mass index (BMI), Caprini score (≤2, ≥3), nutritional risk screening 2002 (<3, ≥3), Eastern Coopera-tive Oncology Group performance status (0, 1), preoperative hypersensitive C-reactive protein, preoperative IL-6, preoperative white blood cell count, preoperative albumin were 19, 11, 59.00(51.25,65.25)years, 21.92(20.93,22.73)kg/m 2, 7, 23, 24, 6, 18, 12, 0.78(0.78,1.46)mg/L, 3.07(1.50,10.56)μg/L, 6.07(4.94,7.19)×10 9/L, 44.30(40.83, 46.15) g/L in the 30 patients of TPTLDG group, versus 21, 8, 57.00(51.00, 67.00)years, 21.90(20.95, 23.35)kg/m 2, 11, 18, 24, 5, 17, 12, 1.13(0.78,11.40)mg/L, 5.56(1.88,15.12)μg/L, 5.54(4.71,6.70)×10 9/L, 43.55(40.25,44.88)g/L in the 29 patients of FPLDG group, showing no significant difference in the above indicators between the two groups ( χ2=0.557, Z=-0.444, -0.805, χ2=1.482, 0.074, 0.012, Z=-1.259, -1.262, -0.819, -1.199, P>0.05), confounding bias ensured comparability between the two groups. (2) Comparison of perioperative condition. The length of incision, time to removing drainage tube, IL-6 at postoperative day 3, cost of hospital stay were 6.65(6.48,6.93)cm, 3.00(0,3.00)days, 29.18 (13.67, 43.53)μg/L, 84 164.15(73 084.72, 96 782.14)yuan in the TPTLDG group, versus 8.00(7.50,8.35)cm, 3.00(3.00,4.00)days, 47.56(21.31,85.79)μg/L, 92 120.43(87 069.33, 113 089.74)yuan in the FPLDG group, showing significant differences in the above indicators between the two groups ( Z=-11.065, -2.141, -2.940, -2.220, P<0.05). (3) Comparison of complications during postoperative 30 days. The incidence rate of complications during postoperative 30 days was 30.00%(9/30) and 24.14%(7/29) in the TPTLDG group and FPLDG group, respectively, showing no significant difference between the two groups ( χ2=0.256, P>0.05). (4) Comparison of pathological examination. Cases with pathological N staging as 0 stage, 1 stage, 2 stage, 3 stage were 22, 2, 4, 2 in the TPTLDG group, versus 13, 7, 4, 5 in the FPLDG group, showing a significant difference between the two groups ( Z=-2.021, P<0.05). Conclusion:TPTLDG is safe and feasible for gastric cancer, with a good short-term efficacy.

In recent years, organ donation and transplantation have entered a stage of steady development in China. Nevertheless, the shortage of transplant organs and the contradiction between supply and demand of organs are still the bottlenecks to achieve the strategy of "self-sufficiency in organ transplantation" advocated by the World Health Organization (WHO). The key reasons for donor loss described in the "critical pathway of organ donation" defined by the WHO include the identification and referral of potential donors and the maintenance and repair of organs. Smooth development, high efficiency and high-quality development of organ donation cannot be achieved without the support of intensive care medicine, which are highly associated with the cognition, recognition and participation of intensive care unit(ICU) staff. In this article, research progress in ICU staff’s cognition, attitude and willingness for organ donation were reviewed and relevant influencing factors were discussed, aiming to offer targeted suggestions on how to resolve these difficulties.