AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P＜0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P＜0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P＜0.01),which was improved by GL treatment(P＜0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P＜0.01),which was restored in CDDP+GL group(P＜0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P＜0.01),which was restored in CDDP+GL group(P＜0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.

Objective:To investigate the mechanism of Yunshi Ganmao Heji against respiratory syncytial virus (RSV) infection based on network pharmacology and in vivo experiments. Methods:Network pharmacological prediction: Several databases including TCMSP and GeneCards were used to predict the active ingredients and targets of Yunshi Ganmao Heji in the intervention of RSV infection. Cytoscape 3.2.1 software was used to construct the traditional Chinese medicine component-disease target network diagram. The interactions between proteins were analyzed by STRING database. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using Metascape database. Molecular docking technology was used to verify the results of network pharmacology. Experimental verification of Yunshi Ganmao Heji for the intervention of RSV infection: A mouse model of RSV infection was established through intranasal infection. After the administration of Yunshi Ganmao Heji, blood routine test results, lung indexes and pathological changes in lung tissue were analyzed. Peripheral blood T cell subsets were detected by flow cytometry. The levels of TNF-α, IL-6 and IL-1β in serum were detected by ELISA. RT-PCR was used to detect the relative expression of TLR4, NF-κB and RSV-N gene at mRNA level in lung tissues.Results:A total of 41 active ingredients of Yunshi Ganmao Heji and 111 drug targets for RSV infection were obtained. Besides, 167 signaling pathways mainly including PI3K/AKT, MAPK and Toll-like receptor signaling pathways were obtained. Molecular docking results showed that the binding energies of luteotin, kaempferol and quercetin, three active ingredients of Yunshi Ganmao Heji, with RSV-G, RSV-F, PI3K, AKT1 and Bcl-2 were less than 0 kcal/mol. In vivo experiment results showed that compared with RSV group, the counts of white blood cells and lymphocytes increased and the lung index decreased in high-dose Yunshi Ganmao Heji group, with statistically significant difference ( P<0.05). HE staining showed pulmonary hyperplasia, thickened alveolar wall and inflammatory cell infiltration in interstitium in RSV group. Alveoli in ribavirin group as well as low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups tended to be of uniform size, and the alveolar walls was roughly uniform in thickness. Compared with RSV group, the low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups showed significantly increased numbers of CD3 +, CD4 + and CD8 + T lymphocytes, decreased CD4 + /CD8 + T cell ratio, lower levels of TNF-α, IL-6, IL-1β in serum, and reduced viral load and inhibited expression of TLR4 and NF-κB at mRNA level in lung tissues ( P<0.05). Conclusions:Yunshi Ganmao Heji can regulate RSV infection by targeting multiple targets and pathways with several active ingredients. Its main functions are to alleviate pathological injury in lung tissues and reduce inflammatory response, and the possible mechanism underlying the antiviral functions may be related to its inhibitory effect on the activation of TLR4/NF-κB pathway.

Compared with other drug loading methods,PLGA drug-loaded microspheres have the advantages of sustained and con-trolled release ability,biodegradability,drug release stability,and targeted delivery function,which have become a research hotspot in pharmaceutics.With the improvement of the preparation technology and the quality of microspheres,they have been gradually promoted in clinical practice,and have achieved remarkable results in the treatment of tumors,osteoarthritis,diabetes,eye diseases and so on.However,there is still a lack of systematic review on the application of PLGA microspheres in stomatology.This article aims to intro-duce the clinical application characteristics of PLGA microspheres,and review their application prospect in oral and maxillofacial tumors,temporomandibular joint diseases,periodontitis,caries and alveolar bone defects,so as to provide reference for their applica-tion in stomatology.

Objective:To investigate the efficacy and safety of tocilizumab in the treatment of critically ill children with acute necrotizing encephalopathy (ANE).Methods:It is a retrospective cohort study. The children with ANE admitted to the pediatric intensive care unit of 4 Chinese tertiary hospitals from December 2022 to November 2023 were divided into conventional treatment group and tocilizumab group, and the comparison between groups was performed by using Mann ‐ Whitney U test or Chi-square test. Results:Among 21 cases of severe ANE, there were 11 males with the onset age of 65 (27, 113) months. The duration from onset to PICU admission was 2 (1, 2) days. There were 13 cases of ultra-high fever (greater than 40 ℃), including 18 cases of convulsions, and 19 cases with a GCS score of less than 8 points. The causative agent was novel coronavirus Omicron in 7 cases and influenza A in 14 cases. All cases had central respiratory failure requiring mechanical ventilation. Of the 21 cases, 18 were shock, 15 were coagulopathy, 10 were kidney injury and 13 were liver dysfunction. Of these hospitalized patients, 8 children with ANE were treated with tocilizumab. Eight cases received continuous blood purification (CBP) treatment, 5 of them were combined with plasmapheresis. Serum cytokine levels were elevated in 21 children with ANE, including (interleukin, IL)-6 and IL-8 (61 (22, 1 513) and 68 (5, 296) ng/L). There were 14 cases (67%) deaths, including 11 cases in the conventional treatment group and 3 cases in the tocilizumab group. There was no significant difference in the mortality rate between the two groups ( P=0.056). Tocilizumab-related rash or other adverse events were not observed. Conclusions:The motality of critically ill ANE patients was high. The combination of Tocilizumab with conventional treatment did not reduce the motality of severe ANE patients, and no adverse reactions of tocilizumab were observed.

Objective:To systematically evaluate the clinical efficacy and safety of Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction.Methods:All RCTs about Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction were retrieved from CNKI, Wanfang Database, VIP database, PubMed and CBM. The search period was from the database establishment to December 31, 2021. Two researchers independently extracted the basic literature data and evaluated the methodological quality, then used RevMan5.4 software for meta-analysis.Results:Totally 9 articles were included, involving a total of 988 patients, including 505 cases in the observation group and 483 cases in the control group. Meta-analysis showed that the total effective rate of Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction was higher than that of conventional Western medicine [ RR=1.20, 95% CI (1.13, 1.27), P<0.05]. At the same time, the effect of NIHSS score, Barthel score and FIB were better than those of conventional Western medicine [respectively: MD=-3.21, 95% CI (-4.45, -1.97), P<0.05; MD=11.83, 95% CI (10.66, 13.00), P<0.05; MD=-0.95, 95% CI (-1.36, -0.54), P<0.05]. After treatment with Xixian Tongshuan Capsules/Pills combined with Western medicine, the adverse reactions mainly included dizziness, nausea, indigestion, rash, facial blushing, etc. There was no statistically significant difference in safety between the two groups [ RR=1.50, 95% CI (0.75, 3.01), P>0.05]. Conclusions:Under the treatment of conventional Western medicine, the addition of Xixian Tongshuan Capsules/Pills can improve the clinical efficacy of cerebral infarction treatment, effectively improve the symptoms of neurological impairment, improve the ability of daily life, and promote the prognosis and recovery, and without increasing the incidence of adverse reactions. However, large sample and high quality studies are still needed to support the conclusion.

The interleukin (IL) -23/IL-17 axis is the main pathway in the pathogenesis of plaque-type psoriasis vulgaris, and IL-17A plays a key role in the relevant immune pathways. IL-17A mediates overlapping inflammatory pathways in atherosclerosis and psoriasis, promotes inflammation, coagulation and thrombosis, and plays an important role in the occurrence and development of cardiovascular comorbidities in patients with psoriasis. Inhibiting the inflammatory effect of IL-17A can reduce the incidence and mortality of cardiovascular comorbidities in patients with severe psoriasis. This review summarizes recent research progress in IL-17A-mediated systemic inflammation and cardiovascular comorbidities in patients with psoriasis, and provides a reference for prevention and reduction of cardiovascular comorbidities in patients with psoriasis in clinical practice.

Objective:To analyze clinical characteristics of neurosyphilis patients with abnormal mental behaviors as the initial symptom, and to provide a reference for clinical classification of, as well as outcome prediction and efficacy monitoring in neurosyphilis.Methods:Clinical data were collected from 67 HIV-negative neurosyphilis patients with abnormal mental behaviors as the initial symptom in the Second Affiliated Hospital of Soochow University from November 2012 to November 2019, and retrospectively analyzed. Statistical analysis was carried out by using t test. Results:Among the 67 patients, 52 (77.6%) were males, and 15 (22.4%) were females; there were 63 (94.0%) middle-aged and elderly patients and 4 (6.0%) adolescent patients; 38 (56.7%) patients were diagnosed with progressive general paresis, 21 (31.3%) with meningovascular neurosyphilis, 1 (1.5%) with meningeal neurosyphilis, 3 (4.5%) with tabes dorsalis, and 4 (6.0%) with mixed-type neurosyphilis. As laboratory examination showed, 67 patients all presented with positive serum rapid plasma reagin (RPR) test, serum Treponema pallidum particle agglutination (TPPA) test, and cerebrospinal fluid TPPA test, 55 (82.1%) had positive cerebrospinal fluid RPR test, 47 (70.1%) had elevated cerebrospinal fluid protein levels of > 0.45 g/L, 50 (74.6%) had increased white blood cell counts of > 8 ×10 6/L in cerebrospinal fluids, and 28 (41.8%) had elevated IgG levels in cerebrospinal fluids. Magnetic resonance imaging of the brain revealed multiple ischemic foci in 21 (31.3%) cases, multiple leukodystrophy in 17 (25.4%) , cerebral atrophy in 15 (22.4%) , infarction in 8 (11.9%) , and encephalitis-like changes in 2 (3.0%) . Of the 67 patients, 48 were treated with penicillin in aqueous solutions, 15 with ceftriaxone, and 4 with doxycycline. Six months later, the follow-up showed that 46 (68.7%) patients responded to the treatment, and the early course of disease was significantly shorter in the highly responsive group than in the poorly responsive group ( P < 0.05) . Conclusion:The middle-aged and elderly males were predominant in the neurosyphilis patients with abnormal mental behaviors as the initial symptom, magnetic resonance imaging is helpful for clinical classification and prognosis prediction of neurosyphilis, and early and standardized antisyphilitic treatment can markedly improve the prognosis of patients.

【Objective】 To detect the piperacillin and amoxicillin antibodies in suspicious blood samples from pre-transfusion compatibility tests in Wuxi and analyze the general characteristics of them, so as to eliminate the interference of drug-induced antibodies with compatibility tests and provide reference for safe and effective blood transfusion, 【Methods】 Drug-sensitized RBCs and low-ion anti-globulin microcolumn gels were used to detect piperacillin and amoxicillin antibodies in 128 plasma samples which were initially undetermined in pre-transfusion compatibility tests. Data were analyzed by Chi-square test or fisher′s exact test. P<0.05 was statistically significant. 【Results】 Among these 128 undetermined samples, including 31 cases of type A, 48 type B, 14 type AB and 35 type O, the overall positive rate of piperacillin and amoxicillin antibodies was 28.9%(37/128), in which the positive rates of piperacillin and amoxicillin antibodies were 20.3%(26/128) and 8.6%(11/128), respectively. The difference between these two drug-induced antibodies was significant(P<0.05). Further analysis showed that the piperacillin antibodies in patients over 50 years old was 25.3%(24/95), while under 50 years old was 6.1%(2/33)(P<0.05). In contrast, the amoxicillin antibodies in patients over 50 years old was 5.3%(5/95), while under 50 years old was 18.2%(6/33), with statistically significant differences between each other(P<0.05). 【Conclusions】 In patients with suspicious antibodies in pre-transfusion detection, except for the allotype antibodies, drug-induced antibodies should be more considered in combination with medication history to better ensure the safety and effectiveness of blood transfusion.