ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

Malaria remains one of the most serious public health problems worldwide. After China achieved the target for malaria elimination, thousands of imported malaria cases are still reported annually. Timely and accurate diagnosis is critical to clinical treatment of cases and prevention of re-establishment of imported malaria. Detection of Plasmodium antigens is one of the criteria for definitive diagnosis of malaria. Malaria rapid diagnostic tests (RDTs) based on the immunochromatographic assay have become an important tool for clinical diagnosis of malaria due to convenient procedures and rapid detection. Nevertheless, there are still multiple misunderstandings pertaining to use of malaria RDTs among workers in medical and disease control and prevention institutions at all levels across China. To standardize technical guidelines and operational procedures for detection of Plasmodium spp., the National Disease Control and Prevention Administration has arranged the formulation of a recommended health industry standard Detection of Plasmodium spp. Immune-chromatographic test (WS/T 10029—2025), which has been officially iming immunochromatographic assays, including the testing principles, sample collection and detection procedures, and result interpretation, which provides the technical basis and operational specifications for detection of Plasmodium antigens in medical and disease control and prevention institutions at all levels. Based on analysis of the epidemiological characteristics of imported malaria in China, this article interprets the core content of this standard, aiming to promote its dissemination, implementation, and practical applications.

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.

Objective:To study and analyze the brain networks of hemiplegic stroke patients in a resting state or during virtual reality(VR)upper limb rehabilitation robot training by functional near-infrared spectroscopy(fNIRS).Method:Fourteen hemiplegic stroke patients were included in this study as the test group,while 14 healthy subjects were recruited as the control group.The fNIRS data of the two groups were collected during the rest-ing state or the VR upper limb rehabilitation robot training.The functional connectivity(FC)index of the brain network was calculated.Result:①No significant difference was found between the test group and the control group in FC in the rest-ing state(P>0.05).②The overall FC of the control group did not increase significantly in the VR task com-pared with the resting state(P>0.05).But the FC of the LSMA-RPFC increased significantly(P<0.05).③The overall FC of the test group decreased in the VR task compared with the resting state(P<0.05),of which the LSMA-RPFC decreased(P<0.05).④The overall FC of the test group was lower than that of the control group(P<0.05),in which there was a significant difference in FC between LSMA-RSMA,LSMA-LM1,LS-MA-RM1,LSMA-RS1,and LM1-RS1(P<0.05)when the test group and the control group performed the VR upper limb rehabilitation robot training task.Conclusion:VR upper limb rehabilitation robot training can induce plastic reorganization of the extensive sen-sorimotor network in hemiplegic patients with stroke.And the mechanism of improving upper limb function may be related to the FC changes between bilateral SMA and SMA and other brain regions.

Objective To investigate the current status and influencing factors of anticipatory grief of main caregivers of young and middle-aged patients with advanced liver cancer by cross-sectional survey.Methods A total of 330 caregivers of young and middle-aged patients with advanced liver cancer who were admitted to The Third Affiliated Hospital of Naval Medical University from January 2023 to May 2023 were enrolled as research objects by convenience sampling.A questionnaire survey on general information,anticipatory grief and simple coping style was conducted on these caregivers one day before discharge.Results The score of anticipatory grief of the caregivers was 94.10±22.33.Multiple linear stepwise regression analysis was performed with statistically significant data from the characteristics of the research objects as independent variables and anticipatory grief as the dependent variable,and the result showed that gender,monthly income,educational level,personality self-assessment and coping were main factors affecting anticipatory grief of main caregivers of young and middle-aged patients with advanced liver cancer(all P<0.05).The mean score for positive response was 2.23±0.14,which was negatively associated with anticipatory grief(P=0.041).The mean score for negative response was 1.31±0.24,which was positively associated with anticipatory grief(P<0.001).Conclusion The anticipatory grief of main caregivers of young and middle-aged patients with advanced liver cancer is at a high level.The anticipatory grief is negatively related to positive coping,and positively related to negative coping.The main factors affecting anticipatory grief of main caregivers of young and middle-aged patients with advanced liver cancer are gender,family economic status,educational level,and introverted personality.

Objective:To study and analyze the brain networks of hemiplegic stroke patients in a resting state or during virtual reality(VR)upper limb rehabilitation robot training by functional near-infrared spectroscopy(fNIRS).Method:Fourteen hemiplegic stroke patients were included in this study as the test group,while 14 healthy subjects were recruited as the control group.The fNIRS data of the two groups were collected during the rest-ing state or the VR upper limb rehabilitation robot training.The functional connectivity(FC)index of the brain network was calculated.Result:①No significant difference was found between the test group and the control group in FC in the rest-ing state(P>0.05).②The overall FC of the control group did not increase significantly in the VR task com-pared with the resting state(P>0.05).But the FC of the LSMA-RPFC increased significantly(P<0.05).③The overall FC of the test group decreased in the VR task compared with the resting state(P<0.05),of which the LSMA-RPFC decreased(P<0.05).④The overall FC of the test group was lower than that of the control group(P<0.05),in which there was a significant difference in FC between LSMA-RSMA,LSMA-LM1,LS-MA-RM1,LSMA-RS1,and LM1-RS1(P<0.05)when the test group and the control group performed the VR upper limb rehabilitation robot training task.Conclusion:VR upper limb rehabilitation robot training can induce plastic reorganization of the extensive sen-sorimotor network in hemiplegic patients with stroke.And the mechanism of improving upper limb function may be related to the FC changes between bilateral SMA and SMA and other brain regions.

Objective:To evaluate the efficacy of individualized removal therapeutic regimen for donor-specific antibodies (DSA) and examine its related influencing factors.Method:From January 2016 to January 2021, 34 recipients of kidney transplant (KT) underwent regular DSA testing and the results were positive. DSA removal therapy based upon rituximab (RTX) plus intravenous immune globulin (IVIG) was offered. Correlation between DSA negative conversion rate and DSA types, time from start of treatment to transplantation, HLA loci targeted by DSA and DSA mean fluorescent intensity (MFI) were analyzed retrospectively. Changes of immunedominant DSA (iDSA) and serum creatinine in individuals with de novo DSA (dnDSA) before and after treatment were also examined.Results:At Month 3 post-treatment, antibodies turned negative in 17/34(50.0%) patients and DSA became negative in 19/34(55.9%) at the last follow-up. Then we identified 78 DSA from all patients. No significant difference existed in negative conversion rate of pfDSA and dnDSA at Month 3 post-treatment [62.9%(39/62) vs 37.5%(6/16)] and at the last follow-up [4.2%(46/62) vs 56.3%(9/16)]( P=0.067, 0.219). For pfDSA, negative conversion rate of pfDSA with different MFIs after 3-month treatment varied significantly [negative conversion rate of weak positive DSA was 78.6%(33/42) and positive and above DSA 30%(6/20), P<0.001]. It was an independent related factor of whether or not pfDSA could turn negative (48.6%, 95% CI: 22.3%-66.8%, P=0.001). At the last follow-up, negative conversion rate of pfDSA differed markedly at different timepoints from start of treatment to transplantation [treated within 30 days post-operation was 79.2%(42/53) and over 30 days post-operation was 44.4%(4/9), P=0.042] and among different DSA MFI [88.1%(37/42) of weakly positive DSA and 45%(9/20) of positive and above DSA, P<0.001] and they were independent related factors for negative conversion of pfDSA (34.8%, 95% CI: 3.2%-61.8%, P=0.008; 43.1%, 95% CI: 18.5%-63.4%, P=0.001). Mean decline rate in iDSA was 66.67% at Month 3 post-treatment and 77.90% at the last follow-up. The difference was statistically significant ( P=0.035). Serum level of creatinine of 9 patients with dnDSA was (110.2±26.9) μmol/L pre-treatment, (178.8±90.5) μmol/L during treatment, (153.9±72.8) μmol/L at Month 3 post-treatment and (213.6±185.8) μmol/L at the last follow-up. Serum creatinine rose during treatment ( t=-2.794, P=0.023), declined at Month 3 post-treatment ( t=3.430, P=0.009) and spiked again at the last follow-up ( P=0.028). Conclusion:After DSA removal therapy based upon RTX plus IVIG, negative conversion rate of pfDSA is correlated with its MFI and time from start of treatment to transplantation. There is no significant rebound in DSA MFI and graft function of dnDSA patients improves immediately after treatment.

In recent years, targeted therapy and immunotherapy have been applied more and more widely in tumor treatment, and reports on psoriasis induced or exacerbated by these drugs have emerged continuously. This review summarizes and evaluates targeted therapeutic drugs and immunotherapeutic drugs that allegedly induce or aggravate psoriasis according to their targets and possible mechanisms, including programmed death receptor 1 inhibitors, epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, anti-CD20 monoclonal antibodies, phosphoinositide 3-kinase δ inhibitors and multi-targeted drugs. In most cases, the relationships between drugs and the occurrence of psoriasis are possible or probable, and in only a few cases the causality is certain.

Objective To construct curcumin pyrazole derivative by the reaction of diketone of curcumin and benzylhydrazine based on the above structure-activity relationship,and to explore its antioxidant activity to provide experimental basis for the development of curcumin antioxidant derivative.Methods Curcumin-N-substituted pyrazole derivative was synthesized from curcumin and benzylhydrazine.The structures of the derivative were confirmed by infrared spectroscopy(IR),nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR)and LC-MS.The antioxidant activity in vitro of the derivative was evaluated by determination of curcumin and its pyrazole derivative scavenging ability for 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid(ABTS)free radical.Results Curcumin pyrazole derivative was successfully synthesized.Curcumin and its pyrazole derivative showed good free radical scavenging effects in the range of 4.6-73.6,6.25-100 μg·mL-1,respectively,with a significant dose-effect relationship.The half-maximal inhibition(IC50)values of curcumin and its pyrazole derivatives determined by DPPH method were 14.24,40.37 μg·mL-1,respectively,while the IC50 values of curcumin and its pyrazole derivatives determined by ABTS method were 36.65,19.26 μg·mL-1,respectively.Conclusion The antioxidant activity of β-dione of curcumin was retained through the substitution of the pyrazole ring,and the curcumin pyrazole derivative deserves further investigation as a potential antioxidant.