To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS). Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of 151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cfPWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling. Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2 rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a 19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Background: Artificial intelligence-assisted image recognition technology is currently able to detect the target area of an image and fetch information to make classifications according to target features.This study aimed to use deep neural networks for computed tomography(CT)diagnosis of perigastric metastatic lymph nodes(PGMLNs)to simulate the recognition of lymph nodes by radiologists,and to acquire more accurate identification results.Methods: A total of 1371 images of suspected lymph node metastasis from enhanced abdominal CT scans were identified and labeled by radiologists and were used with 18,780 original images for faster region-based convolutional neural networks(FR-CNN)deep learning.The identification results of 6000 random CT images from 100 gastric cancer patients by the FR-CNN were compared with results obtained from radiologists in terms of their identification accuracy.Similarly,1004 CT images with metastatic lymph nodes that had been post-operatively confirmed by pathological examination and 11,340 original images were used in the identification and learning processes described above.The same 6000 gastric cancer CT images were used for the verification,according to which the diagnosis results were analyzed.Results: In the initial group,precision-recall curves were generated based on the precision rates,the recall rates of nodule classes of the training set and the validation set; the mean average precision(mAP)value was 0.5019.To verify,the results of the initial learning group,the receiver operating characteristic curves was generated,and the corresponding area under the curve(AUC)value was calculated as 0.8995.After the second phase of precise learning,all the indicators were improved,and the mAP and AUC values were 0.7801 and 0.9541,respectively.Conclusion: Through deep learning,FR-CNN achieved high judgment effectiveness and recognition accuracy for CT diagnosis of PGMLNs.

OBJECTIVETo evaluate the effect of early application of recombinant human erythropoietin (rhEPO) on white matter development in preterm infants using fractional anisotropy (FA) of magnetic resonance diffusion tensor imaging (DTI).

METHODSA total of 81 preterm infants with gestational age ≤32 weeks, birth weight <1 500 g, and hospitalization within 24 hours after birth were randomly divided into rhEPO group (42 infants) and control group (39 infants). The infants in the rhEPO group were administered rhEPO, while those in the control group were given the same volume of normal saline. The preterm infants of both groups took examinations of head magnetic resonance imaging, diffusion-weighted imaging, and DTI at the corrected gestational age of 35-37 weeks. FA was calculated for the regions of interest in both groups.

RESULTSThere was no significant difference in the incidence of intracranial hemorrhage, periventricular leukomalacia, focal cerebral white matter damage (CWMD), and extensive CWMD between rhEPO and control groups (P>0.05). Compared with the control group, the rhEPO group showed higher FA values at the posterior limb of the internal capsule, the splenium of the corpus callosum, frontal white matter, and occipital white matter (P<0.05). There was no significant difference in FA values at the parietal white matter, thalamus, lenticular nucleus, and caudate nucleus between the two groups (P>0.05).

CONCLUSIONSEarly application of rhEPO has a neuroprotective effect on white matter development in preterm infants.

Diffusion Tensor Imaging ; Erythropoietin ; pharmacology ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Neuroprotective Agents ; pharmacology ; Recombinant Proteins ; pharmacology ; White Matter ; drug effects ; growth & development

OBJECTIVETo test the effect of asarinin, the extract of Herba Asari, on the acute heart transplantation rejection and the expression of adhesion molecule.

METHODAsarinin was extracted from herba asari. 64 SD rats undergone heart transplantation were divided into four groups: group A (control group), group B (Cyclosporine A treated), group C (Asarinin treated), and group D (1/2 CsA and 1/2 Asarinin). Some rats were used to examine survival time (n = 8) and the others were used to observe the pathological injury and the expression level of interrellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-I (VCAM-1) by using immunohistochemistry.

RESULTAsarinin could prolong the survival time of allografts, which was similar to CsA group (P > 0.05). Asarinin could relieve the damage of cardiomyocytes of the transplanted. Asarinin could also decrease the level of ICAM-1 and VCAM-1 in the allografts.

CONCLUSIONAsarinin may play important roles in suppressing the immune rejection, prolong the allografts survival time and protect the donor organ, which was similar to CsA. The expression level of ICAM-1 and VCAM-1 is increased in suppressing the course of acute rejection and asarinin can inhibit their expression level. Asarinin can decrease the dosage of CsA.

Animals ; Asarum ; chemistry ; Dioxoles ; isolation & purification ; pharmacology ; Graft Rejection ; metabolism ; Graft Survival ; drug effects ; Heart Transplantation ; Intercellular Adhesion Molecule-1 ; metabolism ; Lignans ; isolation & purification ; pharmacology ; Male ; Myocardium ; metabolism ; pathology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Vascular Cell Adhesion Molecule-1 ; metabolism

Objective:To evaluate the impact and analyze the mechanism of separating drug sales from medical services reform on the total medical expenditure containment of outpatient services in Beijing. Methods:The monitoring data and historical data from 89 third-level,78 second-level public hospitals,and 206 primary health institutions and community health service agencies,which participated in the reform,were analysed to estimate the impacts on outpa-tient service utilization and service price. The analysis was based on the data of the first and second quarters of 2016 outpatient and emergency department fee changes,and analysis of service utilization and service price factors on the im-pact of changes in outpatient and emergency services mechanism. Results:The total outpatients'expenditure in Beijing in the second quarter of 2017 was 17.38 billion yuan,representing a slight decrease of 1.14% than the expenditure in 2016. The growth rate reduced by 2.46%. Expenditure in third-level and second-level hospitals decreased by 2.82% and 3.02%,respectively,with reductions in growth rates of 4.06% and 3.74% respectively. Expenditure in primary institutions increased by 17.09%. The increase rate in the second quarter of 2017 was 26.28%,representing a remark-able increase compared to the rate in 2016(15.84%). The contribution from the medical institution service prices and service utilization to the change of outpatient and emergency medical expenditure containment was 6.98% and -7. 65%,respectively. For third-level hospitals,the contribution was 10.37% and -12.00%,respectively;second-level hospitals were 0.72% and -3.35%,respectively;and the primary health institutions was 6.08% and 9.57%. Con-clusions:Beijing's comprehensive reform of separating drug sales from medical services reform has effectively controlled the rising medical expenditure of outpatient services,mainly by adjusting outpatients service utilization between differ-ent level healthcare institutions.

Guillain-Barre syndrome (GBS) is an autoimmune disease on the injury of peripheral nerve myelin proteins or axon, of which the acute motor axonal neuropathy (AMAN) as a subtype is of infrequence and an extremely low incidence of post-operation. This article originally reported one case from Peking University People's Hospital on successful treatment of severe GBS (AMAN) on post-operation with renal carcinoma and meningioma. The diagnostic criteria of AMAN refer to AIDP, of which the feature of AMAN suggests a pure motor nerve dysfunction and significant damage on motor axon. It is reported that infection and surgery may induce GBS. The positive result of IgM and IgG was considered the application of ganglioside and blood-brain barrier might be damaged after meningioma surgery which eased the drug to enter the cerebrospinal fluid circulation and induced lesions, therefore the etiology on this GBS case was of high confidence of administrating ganglioside drugs. Autonomic nerve dysfunctions, such as blood pressure fluctuations and arrhythmia could be caused in GBS, of which about 3%-10% of GBS patients would die. Early use of gamma globulin or plasma exchange was recommended internationally, but recently some new ideas, to some extent, of significance on GBS treatment emerged. However, there was still no consensus on GBS treatment systematically all over the world. Till now, the general treatment program on GBS may be still gamma globulin or plasma exchange and a curious judgment of prognosis is essential in order to make a reasonable plan. That it was usually of no omen on severe autonomic nerve dysfunction must be successively monitored, the same as the management of the respiratory tract and nutrition support. The key measures taken on lung recruitment was postural drainage on this case with a low cost but a qualified effectiveness. This case report aimed to deepen the understanding of AMAN and acquaint the cutting-edge advances on the treatment of GBS, as well as providing successful treatment experience for the prevention on similar cases.
Carcinoma, Renal Cell ; Guillain-Barre Syndrome ; Humans ; Kidney Neoplasms ; Meningeal Neoplasms ; Meningioma

Carcinoma, Renal Cell ; complications ; Guillain-Barre Syndrome ; complications ; Humans ; Kidney Neoplasms ; complications ; Meningeal Neoplasms ; complications ; Meningioma ; complications

Objective:To investigate the clinicopathological characteristics, gene mutation profile, and prognostic factors of diffuse large B-cell lymphoma (DLBCL) in female genital tract.Methods:A retrospective analysis was performed on the clinicopathological data of 30 patients with female genital tract DLBCL who were admitted to Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2003 to October 2021. Targeted sequencing was used to detect 55 lymphoma-related genes, and the gene mutation status of patients was evaluated. Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed by Cox proportional hazards model.Results:The median age of 30 female genital tract DLBCL patients at diagnosis was 58 years old (23-77 years old). The initial symptoms mainly included abdominal pain, distension, and masses (8 cases, 32%). Tumors most commonly located in the adnexal region (including ovaries and fallopian tubes) (13 cases, 45%), of which 9 cases were unilateral. Twenty-one cases (70%) had multiple extra-nodal involvements, 22 cases (73%) had Ann Arbor stage Ⅲ-Ⅳ, 8 cases (27%) had Eastern Cooperative Oncology Group (ECOG) score of ≥2, and 22 cases (73%) had elevated lactate dehydrogenase (LDH), 21 cases (70%) had International Prognostic Index (IPI) score of 3-5. Within 30 patients, 11 patients (37%) received surgery, and all patients received R-CHOP regimen-based chemotherapy. All 30 cases were evaluated for efficacy, the complete remission rate was 83% (25/30), the 5-year progression-free survival (PFS) rate was 69.7%, and the 5-year overall survival (OS) rate was 79.6%. Univariate analysis showed that ECOG score ≥2 was associated with worse OS ( P = 0.048). Among the 30 patients, 7 patients (23%) were primary and 23 patients (77%) were secondary. The proportions of patients with Ann Arbor stage Ⅲ-Ⅳ, IPI score 3-5 and elevated LDH in secondary patients were higher than those in primary patients (all P < 0.001), but there were no significant differences in PFS and OS between the two ( P values were 0.261 and 0.671). The targeted sequencing results of 16 patients showed that the mutation rates of PIM1, MYD88, KMT2D, TP53, CARD11, CCND3 and GNA13 were all > 20%, and TP53 mutation was associated with poorer PFS and OS ( P values 0.012 and 0.002). Conclusions:Female genital tract DLBCL is a rare invasive extranodal DLBCL with similar survival prognosis in primary and secondary patients. High-frequency mutations of PIM1, MYD88 and TP53 genes may provide new directions for treatment.