Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To investigate the role of hyaluronic acid-mediated motion receptor(HMMR)in the malignant progression of esophageal squamous cell carcinoma(ESCC)cells and its potential molecular mechanisms.Methods:8 samples of ESCC tissues and adjacent paracancerous tissues surgically removed at the Fourth Hospital of Hebei Medical University between January 2018 and December 2020,as well as ESCC cells KYSE-30 and KYSE-150,were collected.Western blotting(WB)and immunohistochemistry(IHC)were used to detect the expression of HMMR in ESCC tissues.RNA interference was used to knock down HMMR expression in KYSE-30 and KYSE-150 cells,and qPCR and WB were used to detect the knockdown effect.The effects of HMMR knockdown on the proliferation and invasion abilities of ESCC cells were detected by CCK-8 assay and Transwell assay,respectively.4-nitroquinoline 1-oxide(4NQO)was used to induce carcinogenesis in mice and establish an ESCC model.H-E staining was used to observe the morphological changes of esophagus,and IHC was used to analyze the expressions of HMMR,FAM83D(family with sequence similarity 83 member D),E-cadherin and N-cadherin in tissues of different degrees of carcinogenesis in mice.Results:The expression level of HMMR in human ESCC tissues was significantly higher than that in adjacent paracancerous tissues(all P<0.05).After HMMR knockdown,the proliferation and invasion abilities of KYSE-30 and KYSE-150 cells were significantly reduced(P<0.05 or P<0.01),and the expression level of FAM83D also decreased(all P<0.01).In nude mouse tumor experiment,the body weight of mice in the 4NQO group was lower than that of the control group(all P<0.05).The results of IHC staining showed that HMMR was highly expressed in tumor tissues(P<0.05),and the expression of HMMR in high-grade intraepithelial neoplasia(HGIN)tissues was significantly higher than that in low-grade intraepithelial neoplasia(LGIN)tissues(P<0.001).HMMR was positively correlated with the expressions of FAM83D and N-cadherin(r=0.724,0.870,all P<0.001),and negatively correlated with the expression of E-cadherin(r=-0.714,P<0.001).Conclusion:HMMR is highly expressed in ESCC tissues and may promote the progression of ESCC by up-regulating FAM83D expression.

AIM:To investigate the molecular mechanisms of KG-1 cell proliferation by profiling its responses to various protein kinase inhibitors.METHODS:CCK-8 assay,real time quantitative PCR(qRT-PCR)and Western-blot were used to detect the effect of various protein kinase inhibitors on KG-1 cell proliferation,the expression levels of mRNA and phosphorylation level of signaling pro-teins in the FGFR1 downstream pathways.RE-SULTS:NVP-BGJ398 and PD173074 effectively in-hibited the proliferation of KG-1 cells,indicative of a crucial role of FGFR downstream signaling.After treatment with FGFR inhibitors,the levels of p-FG-FR1OP2-FGFR1 and p-STAT5 decreased significantly(P<0.001),p-AKT decreased slightly(P<0.05),with-out affecting the p-ERK level(P>0.05).CONCLU-SION:FGFR1OP2-FGFR1 mainly acts on the down-stream STAT5 signaling pathway to promote cell proliferation.Comprehensive protein kinase inhibi-tion analysis is a reliable and direct approach to identify functional drivers of cancer cell prolifera-tion.

Hyperlipidaemic rats were randomly divided into a model group,a total flavonoids from echinops latifolius tausch(TFET)high,medium and low dose group,and a positive control group;meanwhile,healthy rats were selected as a blank control group.The rats in each group were dosed with the corresponding concentrations of TFET,simvastatin and distilled water for 45 consecutive days,and were tested for relevant lipid biochemical indexes,antioxidant indexes and PPARα path-way-related gene expression.The results showed that high-dose TFET could reduce the concentra-tions of TC,TG and LDL-C and increase the concentration of HDL-C very significantly;medium-dose TFET could reduce the concentrations of TC and TG very significantly and reduce the con-centration of LDL-C significantly;and low-dose TFET could reduce the concentrations of TC and LDL-C significantly.High,medium and low doses of TFET can extremely significantly reduce in-crease SOD activity;high and medium doses of TFET can extremely significantly reduce MDA content;high dose of TFET can extremely significantly increase T-AOC activity.The high dose of TFET could extremely significantly increase the expression of PPARα,CYP7A1 and CPT-1 genes in rat liver;the medium dose of TFET could extremely significantly increase the expression of CYP7A1 and CPT-1 genes,and could significantly increase the expression of PPARα gene;the low dose of TFET could extremely significantly increase the expression of CYP7A1 gene,and signifi-cantly increase the CPT-1 gene expression.The results suggest that TFET has antioxidant and lip-id-lowering effects on hyperlipidaemic rats,and its mechanism may be related to the activation of PPARα and its downstream related genes to promote fatty acid β-oxidation.

Objective:To explore the application value of real-time shear wave elastography(SWE)and ultrafast pulse wave velocity(UFPWV)techniques in assessing carotid artery stiffness of patients with gouty arthritis(GA).Methods:A total of 80 GA patients admitted to the First People's Hospital of Yibin from August 2022 to July 2023 were selected as GA group.Among of them,24 cases combined with bone erosion who were confirmed by imaging examination,and 56 cases did not combine with bone erosion.In addition,a total of 40 healthy individuals,who underwent physical examinations in our hospital during the same period,were selected as the healthy control group.SWE and UFPWV were used to detect the maximum,minimum and mean values of Young's modulus values of the vessel wall of common carotid artery,and the pulse wave velocity at the beginning of systole(PWVBS)and pulse wave velocity at the end of systole(PWVES)of the vessel wall of common carotid artery of all subjects,and to assess the hardness of circumferential and longitudinal vessel wall of common carotid artery of them.The differences in Young's modulus values,PWVBS and PWVES between two groups were compared.And then,the correlations between bone erosion and Young's modulus values,PWVBS,PWVES of GA patients were further analyzed.Results:The maximum,minimum,mean values,PWVBS and PWVES in the GA group were respectively(78.80±12.38)kPa,(57.83±7.42)kPa,(67.67±8.38)kPa,(7.06±0.59)m/s and(9.50±0.63)m/s,which were significantly higher than those in the healthy control group(t=11.066,8.216,11.751,14.159,19.118,P＜0.05).The maximum,minimum,mean values,PWVBS and PWVES of GA patients with bone erosion were respectively(82.95±6.37)kPa,(59.59±5.29)kPa,(72.18±7.62)kPa,(7.37±0.43)m/s,(10.43±0.47)m/s,which were significantly higher than those[(77.01±5.32)kPa,(57.08±4.73)kPa,(65.73±4.54)kPa,(6.92±0.39)m/s and(9.10±0.41)m/s]of GA patients without bone erosion,the differences were significant(t=4.309,2.099,4.699,4.586,12.720,P＜0.05).Spearman correlation analysis showed that there was significant correlations between maximum,minimum,mean values,PWVBS,PWVES and the combined bone erosion in GA patients(r=0.602,0.421,0.682,0.647,0.732,P＜0.05).Conclusion:SWE and UFPEV techniques can evaluate the hardness of vascular wall of GA patients,and the hardness of circumferential and longitudinal vessel wall of common carotid artery of GA patient is higher than that of healthy person,and the hardness of circumferential and longitudinal vessel wall of common carotid artery of GA patient with bone erosion is higher.

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

Objective To investigate the differences in human epidermal factor receptor 2(HER-2)expression between urothelial bladder carcinoma(UBC)and upper tract urothelial carcinoma(UTUC)and the relationship between HER-2 expression and disease recurrence and progression.Methods Clinical data of 184 patients with urothelial carcinoma admitted in our hospital during Nov.2015 and Jun.2022 were retrospectively analyzed.The patients were divided into UBC group and UTUC group.The positive expression rate of HER-2,recurrence-free survival(RFS)and progression-free survival(PFS)of the two groups were compared,and the survival curve was drawn.The effects of HER-2 expression on the recurrence and progression of disease were analyzed with Cox proportional hazards model.Results The positive expression of HER-2 was significantly higher in UBC patients than in UTUC patients(49.6％vs.32.2％,P=0.027).Among UTUC patients,there was no statistically significant difference in the positive expression of HER-2 in those with renal pelvis cancer and ureteral cancer(30.6％vs.34.8％,P＞0.05).Cox analysis showed that HER-2 positive expression affected UBC recurrence(P＜0.001),but had no effects on the recurrence and progression of UTUC;HER-2 positive expression(P＜0.001),tumor diameter ≥3 cm(P＜0.001),stage ≥T2(P=0.003)and multiple tumor foci(P=0.033)affected the progression of UBC.Conclusion The positive expression of HER-2 is significantly higher in UBC than in UTUC,which can increase the risk of recurrence and progression of UBC,but has no significant effects on the recurrence and progression of UTUC.HER-2 expression is not recommended to independently predict the risk of recurrence and progression of UTUC.