Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Objective To explore the possible mechanism of Xiebaisan in protecting against allergic asthma in rats from the perspective of host intestinal flora metabolism.Methods SPF SD rats were divided into normal group(NC group),model group(M group),and Xiebaisan group.The allergic asthma rat model was established by ovalbumin.Changes in lung histopathology were observed by HE staining.Colon contents were harvested for 16S rDNA high-throughput sequencing to assess changes in the intestinal flora structure and function.Serum and lung tissue samples were collected for non-targeted metabolomics by Ultra-high performance liquid-time-of-flight mass spectrometer.Results HE staining showed some improvement of lung histomorphology in asthmatic rats in the Xiebaisan group compared with that in the M group.16S rDNA high-throughput sequencing showed that the diversity of intestinal flora was decreased in the M group and increased in the Xiebaisan group compared with the M group,the microecosystem of intestinal was improved.Non-targeted metabolomics of serum showed regulation of amino acid metabolism and the mTOR pathway in the Xiebaisan group,and partially reversed differential metabolite expression in the M group.Non-targeted metabonomics of lung tissue samples showed regulation of carbon metabolism,vascular smooth muscle and cAMP signaling pathways in the Xiebaisan group,and partially reversed differential metabolite expression in the M group.Conclusions The protective effects of Xiebaisan on allergic asthma in rats may be related to improvement of the morphological structure of lung tissue,the diversity of intestinal flora,and regulation of mTOR,vascular smooth muscle contraction,and cAMP pathways,which affect amino acid and carbon metabolism.

OBJECTIVE To explore the enhancement effect of Linggui zhugan decoction （LGZG） regulating autophagy on doxorubicin （DOX） against non-alcoholic fatty liver disease-hepatocellular carcinoma （NAFLD-HCC）. METHODS C57BL/6 mice were randomly divided into blank group， NAFLD-HCC group， LGZG group， DOX group and DOX+LGZG group， with 10 mice in each group. The NAFLD-HCC model was established by intraperitoneal injection of diethylnitrosamine （50 mg/kg） and high-fat diet. The blank group was injected with the same amount of normal saline and fed with ordinary diet. After modeling， administration groups were given LGZG aqueous extract （20 g/kg） intragastrically and/or DOX solution intraperitoneally （8 mg/kg）； the blank group and NAFLD-HCC group were given a constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. The general condition of mice （No.2022-BS-197） was monitored during modeling and drug intervention. After drug intervention， body weight， liver weight and liver coefficient of mice were detected. The histopathologic morphology and fibrosis degree of liver tissue in mice were observed； the levels of blood lipid [the levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C）]， the serum contents of alpha fetoprotein （AFP） and carcinoembryonic antigen （CEA）， and the expressions of marker of proliferation Ki-67， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X （Bax） in liver tissue were all detected as well as protein expressions of microtubule-associated proteins 1A and 1B （LC3）， Beclin1 and selective autophagy adopt proteins P62. RESULTS Compared with the blank group， the activity of mice decreased gradually as time in the NAFLD-HCC group； mental fatigue， disheveled and matte hair were observed， and body weight decreased significantly （P＜0.05）； liver weight had an upward trend， and liver coefficient increased significantly （P＜0.05）. The inflammatory cells of liver tissue were infiltrated， with some cells showing ballooning and small cell hyperplasia， and the degree of liver fibrosis was worsened； serum levels of TC， TG and LDL-C， AFP and CEA contents increased significantly， while HDL-C level decreased significantly （P＜0.05）. The protein expressions of Ki-67 and Bcl-2 in liver tissue were increased significantly （P＜0.05）， while the protein expression of Bax decreased. The protein expression of Beclin1 in liver tissue decreased significantly （P＜0.05）； LC3Ⅱ/ LC3Ⅰ decreased， while the expression of P62 protein increased. Compared with the NAFLD-HCC group， the above indexes of mice were improved to different extents in the DOX group， LGZG group and DOX+LGZG group， and the intervention effect of DOX combined with LGZG were better than those of DOX. CONCLUSIONS LGZG combined with DOX can synergically promote the apoptosis of tumor cells， enhance the sensitivity of NAFLD-HCC chemotherapy， and effectively slow down the occurrence and development of NAFLD-HCC. The mechanism may be related to the regulation of autophagy in tumor cells.

Inflammation， the basic pathological process of many diseases， can occur in various tissues and organs of the body and cause many diseases including cancer. So far， there are thousands of anti-inflammatory drugs on the market， but most of these drugs have adverse reactions of gastrointestinal injury， and can even cause greater damage to the body. In recent years， the research on the repurpose of Chinese medicine is in the ascendant， and the innovative research on the specific antimalarial drug artemisinin has attracted extensive attention from scholars in China and abroad. Artesunate is a water-soluble derivative of artemisinin， which has the characteristics of quick effect and low toxicity. In addition to its significant therapeutic effect on malaria， artesunate also has a potential anti-inflammatory effect. In this review， the anti-inflammatory effect and mechanism of artesunate were elaborated in detail by consulting the relevant literature. It was found that artesunate had good anti-inflammatory effects in the respiratory system， liver injury， osteoarthritis， dermatitis， kidney inflammation， colitis， neuroinflammation， and even in novel coronavirus disease 2019 （COVID-19）. It was concluded that artesunate mainly participated in apoptotic signal transduction， mediated immune regulation， and improved oxidative stress to play an anti-inflammatory role by acting on nuclear factor-κB （NF-κB）， nuclear factor E₂-related factor 2 （Nrf2）， phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/tumor necrosis factor receptor-associated factor 6 （TRAF6）， high mobility group box 1 （HMGB1）/receptor for advanced glycation endproduct （RAGE）， and other pathways. Through the review of the anti-inflammatory effect and mechanism of artesunate， it is expected to provide a reference for the application of artesunate in inflammation resistance and further development and utilization of artesunate in the future.

ObjectiveTo explore the mechanism of Shenqi Gualou Xiebai Banxia Decoction （参芪瓜蒌薤白半夏汤， SGXBD） in the treatment of atherosclerosis. MethodsThirty Apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into five groups： model group， rosuvastatin group， low-， moderate-， and high-dose SGXBD， with six mice in each group. They were fed a high-fat diet to prepare for atherosclerosis model. Another six C57BL/6J wild-type mice were set as the blank group. After modeling， the low-， moderate-， and high-dose SGXBD groups were gavaged with 6.46， 12.92， and 25.84 g/（kg·d） of SGXBD， respectively. The rosuvastatin group was given 1.55 mg/（kg·d） of rosuvastatin tablets by gavage. The blank group and model group were given 0.5 ml saline by gavage. After four weeks， the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in the serum of each group were detected， as well as TC and TG in the liver. The serum bile acid level was detected by enzyme cycling colorimetry. The mRNA and protein expression of peroxisome proliferator-activated receptor γ （PPARγ）， sterol regulatory element-binding protein 2 （SREBP2）， 3-hydroxy-3-methylglutaryl-CoA reductase （HMGCR）， and cholesterol 7α-hydroxylase （CYP7A1） in the liver were detected by real-time RT-PCR and Western blot. ResultsCompared with the blank group， the model group showed significant increases in serum TG， TC， and LDL-C levels， and significant decreases in HDL-C and bile acid levels； the levels of TG and TC in the liver， as well as the expression of SREBP2 and HMGCR proteins and mRNA in the liver significantly increased， while the expression of PPARγ and CYP7A1 proteins and mRNA significantly decreased （all P＜0.01）. Compared with the model group， the rosuvastatin group and high-dose SGXBD group showed significant decreases in serum TG， TC， and LDL-C levels and liver TG and TC levels， and significant increases in bile acid levels； the expression of PPARγ and CYP7A1 proteins and mRNA increased， while the expression of SREBP2 and HMGCR proteins and mRNA decreased； the low-dose SGXBD group showed significant decreases in serum TC and LDL-C levels and liver TC level （P＜0.05 or P＜0.01）. Compared with the rosuvastatin group， the low-dose SGXBD group had a significantly higher liver TC level， while the high-dose SGXBD group had a significantly lower liver TC level， CYP7A1 mRNA level， and PPARγ protein expression level， and a significantly higher SREBP2 protein expression level （P＜0.05 or P＜0.01）. Compared with the low- and moderate-dose groups， the high-dose SGXBD group had significantly lower serum TG and liver TC levels （P＜0.05）. ConclusionSGXBD may improve blood lipid levels and exhibit anti-atherosclerotic effects by regulating the protein level of PPARγ and simultaneously affecting the synthesis of liver cholesterol and the conversion of cholesterol to bile acids.

Objective:To investigate the clinical and pathological features, treatment, and prognosis of gray zone lymphoma (GZL) .Methods:From July 2, 2013, to February 10, 2021, the clinical and pathological features, treatment, and outcomes of five patients with GZL at the Blood Diseases Hospital, Chinese Academy of Medical Sciences were studied retrospectively.Results:There were one male and 4 females, with a median age of 28 (16-51) years at diagnosis. Four patients had mediastinal (thymic) involvement, two of which had superior vena cava obstruction syndrome, and 3 patients had extra-nodal involvement. There was one case with a limited Ann Arbor stage and 4 cases with a progressive stage. Three patients had cHL-like pathomorphology with scattered Hodgkin-like cells, strongly positive for CD20, positive for CD30, and CD15 was negative; the other two patients had both cHL and DLBCL morphology, with some areas resembling Hodgkin cells and some areas resembling immunoblasts, strongly positive for CD30, and CD15 but negative CD20. Two patients were treated with cHL-like regimens for induction and achieved only partial remission; after salvage therapy with enhanced DLBCL-like regimens, all achieved complete remission (CR) . Three patients were treated with enhanced DLBCL-like immunochemotherapy regimens for induction, and two patients were effective, one of whom achieved CR. Four patients who did not achieve CR were given second or third-line salvage therapy, and all of them recovered. One patient lost parity, one died of disease progression at 35.9 months after diagnosis, and the remaining three maintained sustained remission.Conclusions:GZL is uncommon, usually affects younger patients, is mediastinal and is diagnosed using path morphology and immunophenotype. Patients with newly diagnosed GZL appear to be more sensitive to DLBCL-like immunochemotherapy regimens; relapsed or refractory patients were tended with non-cross-resistant combination chemotherapy or with new drugs.

Objective:This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) .Methods:A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model.Results:The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions:PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

OBJECTIVE To study the absorbed components of Xiebai powder in blood. METHODS UPLC-Q-TOF-MS/MS method was adopted. SD rats were randomly divided into blank group and administration group ，with 10 rats in each group. Blank group was given water intragastrically ，and administration groups were given 2 g/mL（by the amount of crude drug ）Xiebai powder solution intragastrically. Administration volume was 11.3 mL/kg，twice a day for 3 days. One point five hours after last administration，blood was taken from the abdominal aorta of each rat ，the serum was processed to obtain the supernatant for analysis；the relevant data in positive and negative ion mode were collected ，and the absorbed components of Xiebai powder in blood were analyzed and identified by using self-built secondary mass spectrometry database and consulting the relevant literature. RESULTS Totally 17 components from Xiebai powder were identified ，among which 6 components came from sovereign Moru salba，7 from minister Cortex Lycii ，12 from assistant Glycyrrhiza uralensis ，i.e. kukoamine A ，chlorogenic acid ，tachiogroside B，astringin，neoglycyrrhizin，glycyrrhizin，azelaic acid ，isoglycyrrhizin，glycyroside，anthocyanin，sebacic acid ，parthenolide， anthocyanin，18β-glycyrrhetinic acid ，6-gingerol，palmitoamide，erucamide. These compounds were mainly flavonoids ，alkaloids and organic acids. CONCLUSIONS In this study ，17 absorbed components of Xiebai powder in blood are preliminarily determined，which are consistent with the effect of Xiebai powder. They may be the pharmacodynamic substances of Xiebai powder.