ObjectiveTo provide a reference for the rational clinical use of cold Chinese medicines by sorting and analyzing their properties， flavors， meridian tropism， primary therapeutic indications， methods of administration， dosages， and precautions as recorded in the 2020 edition of Pharmacopoeia of the People's Republic of China （Chinese Pharmacopoeia）. MethodsCold Chinese medicines for internal and external use included in the 2020 edition of Chinese Pharmacopoeia were entered one by one， and their efficacy， properties， flavors， meridian tropism， methods of administration， dosages， and usage precautions were statistically classified and summarized to guide clinical medication use. ResultsA total of 259 cold Chinese medicines for internal use were included and categorized into 18 efficacy groups， mainly comprising heat-clearing drugs， water-excreting and dampness-draining drugs， and phlegm-resolving， cough- and asthma-relieving drugs. Their predominant flavors were bitter， sweet， and pungent， and they primarily entered the liver， lung， and stomach meridians. The main methods of administration included decocting first， grinding into powder for oral use， or preparing into pills or powders， with most dosages ranging from 9 to 15 g. A total of 83 cold Chinese medicines for external use were included， involving 16 efficacy categories. Their main flavors were bitter， sweet， and pungent， primarily entering the liver， lung， and large intestine meridians. The main external application methods were grinding into powder for topical use or preparing decoctions for fumigation and washing， with most dosages ranging from 9 to 15 g. Whether for internal or external use， cold Chinese medicines should be used with caution or contraindicated in pregnant women. ConclusionThe cold Chinese medicines included in the 2020 edition of the Chinese Pharmacopoeia are mainly suitable for patients with carbuncles， swellings， and coughs. However， in clinical practice， it is necessary to strictly follow the principles of syndrome differentiation and treatment， pay attention to administration methods and dosages， and use cold medicines rationally and effectively to improve clinical efficacy.

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.

OBJECTIVES: To investigate the mechanism of DDX17 for regulating proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) during the development of pulmonary hypertension (PH). METHODS: In murine PASMCs cultured under normoxic or hypoxic conditions, the effects of transfection with si-Ddx17 and insulin treatment, alone or in combination, on cell proliferation and migration were evaluated using Ki-67 immunofluorescence staining, scratch assay and Transwell assay. Western Blotting was performed to detect the changes in protein expression levels of DDX17, 4EBP1, S6, p-4EBP1, and p-S6. In a mouse model of PH induced by intraperitoneal injection of monocrotaline (MCT), the changes in pulmonary vasculature were examined using HE staining following tail vein injection of AD-Ddx17i. RESULTS: The PASMCs in hypoxic culture exhibited significantly enhanced cell proliferation and migration and protein expressions of p-4EBP1 and p-S6, and these changes were obviously reversed by transfection with si-Ddx17. Treatment with insulin significantly attenuated the effect of si-Ddx17 against hypoxic exposure-induced changes in PASMCs. In the mouse model of MCT-induced PH, transfection with AD-Ddx17i obviously alleviated pulmonary vascular stenosis and intimal hyperplasia. CONCLUSIONS The expression of DDX17 is elevated in hypoxia-induced PASMCs and PH mice, and silencing DDX17 significantly inhibits PASMC proliferation and migration in vitro and pulmonary vascular remodeling in PH mice by reducing mTORC1 activity.
Animals ; Cell Proliferation ; Cell Movement ; DEAD-box RNA Helicases/metabolism* ; Myocytes, Smooth Muscle/metabolism* ; Mice ; Pulmonary Artery/cytology* ; Hypertension, Pulmonary/metabolism* ; Mechanistic Target of Rapamycin Complex 1 ; Cells, Cultured ; Muscle, Smooth, Vascular/cytology*

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.

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.

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.

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.

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.

ObjectiveTo investigate the mechanism of Chaihu Shugansan in the treatment of functional dyspepsia in rats based on mitophagy and PTEN-induced kinase 1 （Pink1）/E3 ubiquitin ligase （Parkin）. signaling pathway. MethodAccording to the principle of random grouping， 40 SD rats were assigned into a normal group， a model group， a Chaihu Shugansan group， and a positive drug （domperidone） group， with 10 rats in each group. The rats in other groups except the normal group received tail-clamping stimulation to replicate the model of functional dyspepsia. After each time of stimulation， the rats in the normal， model， Chaihu Shugansan， and positive drug groups were administrated with normal saline， normal saline， Chaihu Shugansan （4.8 g·kg^-1）， and an aqueous solution of domperidone （4.5 mg·kg^-1）， respectively. After 28 days of modeling， the gastric emptying rate and the small intestine propulsion rate of the rats in each group were measured and the tissue samples were collected. Hematoxylin-eosin （HE） staining was employed for observation of damage in gastric antrum tissue， and transmission electron microscopy （TEM） for ultrastructural observation of gastric interstitial cells of Cajal （ICCs）. Immunofluorescence co-localization was adopted to observe the expression of cytochrome c oxidase （COX Ⅳ） and Parkin. Western blot was employed to determine the expression levels of microtubule-associated protein 1， light chain 3 （LC3）， and the mitophagy-associated proteins prohibitin2 （PHB2）， Pink1， Parkin， and ubiquitin-specific protease 30 （USP30）. ResultCompared with the normal group， the modeling decreased the gastric emptying rate and the small intestine propulsion rate （P<0.05）. Compared with the model group， Chaihu Shugansan increased the gastric emptying rate and the small intestine propulsion rate （P<0.05）. The results of TEM showed that Chaihu Shugansan reduced the swelling degree of mitochondria in gastric antrum tissue. Compared with the normal group， the modeling increased the fluorescence intensity of Parkin in mitochondria （P<0.01）， while such increase can be alleviated by Chaihu Shugansan （P<0.01）. Western blotting results showed that compared with the normal group， the modeling up-regulated the protein levels of LC3， Pink1， Parkin， and PHB2 （P<0.05， P<0.01） and down-regulated the protein level of USP30 （P<0.01）. Compared with the model group， Chaihu Shugansan down-regulated the protein levels of LC3， Pink1， Parkin， and PHB2 （P<0.05， P<0.01） and up-regulated the protein level of USP30 （P<0.01）. ConclusionChaihu Shugansan may treat functional dyspepsia by blocking the Pink1/Parkin signaling pathway to inhibit excessive mitochondrial autophagy in ICCs.