Objective To investigated the effects of occupational exposure to N,N-dimethylformamide (DMF) on sterol regulatory element-binding protein (SREBP) and iron metabolism among workers. Methods A total of 20 workers occupationally exposed to DMF were selected as the exposure group, and 15 healthy workers without DMF exposure from the same factory were selected as the control group using the purposive sampling method. DMF exposure levels were assessed in individual samples of the workers. The urinary N-methylformamide (NMF) levels were measured by gas chromatography. The mRNA expression of SREBP-1a, SREBP-1c, and SREBP-2 in peripheral blood was measured by real-time quantitative polymerase chain reaction. Enzyme-linked immunosorbent assay was used to detect serum transferrin, soluble transferrin receptor (sTfR), and ferritin levels. Results The DMF exposure levels among the workers in the control group were below the detection limit, and urinary NMF was undetectable. The median DMF exposure level was 13.30 mg/m³, and the mean urinary NMF level was (9.72±1.78) mg/g Cr among the workers in the exposure group. Compared with the control group, the relative mRNA expression of SREBP-1a, SREBP-1c, and SREBP-2 in peripheral blood of workers in the exposure group increased (all P<0.05), while the levels of transferrin and sTfR decreased (both P<0.01). However, there was no statistically significant difference in serum ferritin levels between the two groups (P>0.05). In the exposure group, urinary NMF level of workers was negatively correlated with the relative mRNA expression level of SREBP-1c in blood [correlation coefficient (r)=-0.50, P=0.03], and positively correlated with the levels of serum transferrin, sTfR, and ferritin (r = 0.63, 0.58, and 0.52, respectively; all P<0.05). Conclusion Occupational exposure to DMF can upregulate the expression of the SREBP family and disrupt iron metabolism, with a potential association between these effects.

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.

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.

Facing escalating public health security challenges,infectious disease hospitals have assumed a pivotal role in fortifying the public health service infrastructure.This paper adopts case-based analytical approach,based on Nantong Third Peo-ple's Hospital(Nantong Infectious Disease Center),to explore the"One Hospital,Two Campuses"development model in infec-tious disease hospitals.It analyzes practical strategies for resource integration,functional optimization,and emergency response mechanisms.In addition,this paper highlights the model's role in enhancing public health service capacity,addressing sudden infectious disease outbreaks,and fostering regional healthcare collaboration.The study aims to offer theoretical insights and prac-tical guidance for further improvements in the public health service system.

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.

Facing escalating public health security challenges,infectious disease hospitals have assumed a pivotal role in fortifying the public health service infrastructure.This paper adopts case-based analytical approach,based on Nantong Third Peo-ple's Hospital(Nantong Infectious Disease Center),to explore the"One Hospital,Two Campuses"development model in infec-tious disease hospitals.It analyzes practical strategies for resource integration,functional optimization,and emergency response mechanisms.In addition,this paper highlights the model's role in enhancing public health service capacity,addressing sudden infectious disease outbreaks,and fostering regional healthcare collaboration.The study aims to offer theoretical insights and prac-tical guidance for further improvements in the public health service system.

AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.

Objective:To investigate the association between programmed cell death protein 1 (PD-1) and its ligand PD-L1 and cytokines in patients with polycystic ovary syndrome (PCOS).Methods:Using the GSE54248 dataset from the GEO database, differentially expressed PD1/PD-L1 pathway-related genes in PCOS were identified and subjected to GO and KEGG pathway enrichment analysis. In this case-control study, totally 105 patients with PCOS (named PCOS group) and 109 non-PCOS patients (named control group) who were treated at the Reproductive Assisted Reproduction Center of the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2023 were recruited. The QBPlex flow cytometry high-throughput multiplex assay was utilized to assess the peripheral blood levels of PD-L1, PD-L2, PD-1, and cytokines in PCOS group and control group. Pearson's method was used for correlation analysis.Results:In PCOS group, the PD-1 level in peripheral blood [2.890 (0.020, 4.540) ng/L] was significantly lower than that of control group [3.370 (2.460, 4.360) ng/L, P=0.008], the PD-L1 level [9.820 (8.860, 10.880) ng/L] was lower than that in control group [10.410 (9.700, 11.160) ng/L, P=0.001]. There was no significant difference in the expression level of PD-L2 between the two groups ( P>0.05). From the GSE54248 dataset, 26 differentially expressed genes were identified, primarily enriched in the PD-1/PD-L1 pathway, Th1 and Th2 cell differentiation, and pathways associated with the production of cytokines involved in inflammatory responses. Compared with control group, PCOS group exhibited a significant decrease in the peripheral blood concentrations of interleukin (IL)-5, IL-9, IL-25, IL-10, growth stimulation expressed gene 2 (ST-2), and Granzyme B, and a significant increase in IL-8, IL-1RA, and tumor necrosis factor-α (TNF-α) levels, with all differences being statistically significant (all P<0.05). PD-1 exhibited positive correlations with the levels of IL-1RA, ST-2, and TNF-α ( r=0.270, P=0.005; r=0.213, P=0.029; r=0.291, P=0.003), while it exhibited negative correlations with the levels of IL-9, IL-25, and Granzyme B ( r=-0.322, P<0.001; r=-0.211, P=0.031; r=-0.369, P<0.001). PD-L1 demonstrated positive correlations with the levels of IL-9, IL-25, and Granzyme B ( r=0.254, P=0.009; r=0.330, P<0.001; r=0.340, P<0.001), and a negative correlation with IL-10 level ( r=-0.373, P=0.009). Conclusion:The expression of PD-1 and PD-L1 in the peripheral blood of PCOS patients is down-regulated, which may be associated with an imbalance in Th1/Th2 cytokines and serve as potential molecular biomarkers for the treatment of PCOS.