BACKGROUND:The specific molecular mechanism of the transformation from normal healthy people to acute cervical spondylotic radiculopathy has not been clear,which needs to be further studied. OBJECTIVE:To investigate the differential expression of serum proteomics between normal healthy people and patients with acute cervical spondylotic radiculopathy,and to find and identify potential specific serum markers between them. METHODS:The serum samples of eight patients with acute cervical spondylotic radiculopathy and eight normal healthy people were collected,and the proteomic screening and analysis were performed by tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology,in order to explore and identify serum proteins differentially expressed in patients with acute cervical spondylotic radiculopathy. RESULTS AND CONCLUSION:A total of 183 significantly differential proteins were screened by tandem mass tag technology,and 11 significantly differential proteins were identified(P＜0.05).Compared with normal healthy people,three differential proteins were significantly up-regulated,including human leukocyte antigen-A,secretoglobin family 1a member 1,and protein 4-hydroxyphenylpyruvate dioxygenase,and seven differential proteins were significantly down-regulated,such as immunoglobulin heavy constant gamma 3,skin factor,and myosin light chain 3,in patients with acute cervical spondylotic radiculopathy.Gene ontology enrichment analysis showed that these differential proteins participated in antigen binding,immunoglobulin receptor binding and other molecular functions.Protein-protein interaction analysis showed that among the common differential proteins between normal healthy people and patients with acute cervical spondylotic radiculopathy,HLA-A,HPD,PSMA3,DMKN,SCGB1A1,and MYL3 were located at the nodes of the functional network,and were closely related to the systems of body immunity,cellular inflammatory response,energy metabolism,and mechanical pressure.The significantly differential proteins HLA-A,HPD and MYL3 were verified by western blot,and the results were consistent with those of proteomics.To conclude,tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology can be used to find the differentially expressed proteins in serum between normal healthy people and patients with acute cervical spondylotic radiculopathy.It is preliminarily believed that HLA-A,HPD and MYL3 may be specific serum markers of acute cervical spondylotic radiculopathy,providing a new direction for further research on its pathogenesis.

Objective:To explore the prognostic value of tumor deposits (TD) by number and anatomical distribution in gastric cancer (GC) patients without lymph node metastasis.Methods:From Aug 2012 to Aug 2018 all 91 GC patients undergoing radical gastrectomy and without nodal metastasis at Yijishan Hospital of Wannan Medical College were enrolled in this study. Patients were divided into L1, L2, and L3 groups according to the number of TD and into Q1 and Q2 groups according to the anatomical regions of the TD.Results:The 3-year overall survival (OS) rates of groups L1, L2, and L3 were 58.9%, 52.1%, and 31.5%, respectively ( χ2=9.769, P=0.008). The 3-year OS rates of groups Q1 and Q2 were 58.9% and 7.1% ( χ2=46.310, P<0.001). The number of TD, their distribution, neural invasion, vascular invasion, tumor size, and pT stage were all related to prognosis by univariate analysis (all P<0.05). Tumor size>4 cm ( HR=2.460, 95% CI:1.307-4.629, P=0.005), distribution of TD (non-perigastric)( HR=3.959, 95% CI:2.077-7.545, P<0.001), neural invasion ( HR=4.299,95% CI:1.953-9.461, P<0.001), and pT 4 stage ( HR=2.283, 95% CI:1.250-4.171, P=0.007) were independent risk factors for prognosis by multivariate analysis. Conclusion:The distribution of TD (non-perigastric) is an independent risk factor for poor prognosis in gastric cancer patients after radical gastrectomy and with negative lymph node metastasis.

Objective:To explore the risk factors for the occurrence of thrombocytopenia (TCP) within 2 weeks after pediatric liver transplantation (LT) and examine the relationship between the occurrence of TCP and prognosis.Methods:From January 2021 to November 2021, clinical data were retrospectively reviewed for 162 pediatric LT recipients aged under 4 years at Organ Transplantation Center of Tianjin First Central Hospital.Based upon the lowest value of platelet count at Week 2 post-operation, they were assigned into two groups of TCP (n=90) and non-TCP (n=72). General preoperative profiles, intraoperative findings, postoperative complications, types of commonly used antibiotics, anticoagulant dosing and prognosis of two groups were compared.Univariate and multivariate analyses were utilized for examining the independent risk factors for TCP.Receiver operating characteristic (ROC) curve was plotted for examining the cut-off value of independent risk factors for diagnosing TCP.Results:Among them, 90 (55.56%) developed TCP within 2 weeks post-operation and 25(15.43%) developed TCP at Day 1 post-operation.The median preoperative platelet count was 178×10 9/L and the lowest value was 65×10 9/L at Day 3(1-4) post-operation with a declining rate of 63.5% and platelet count of recipient normalized at Day 6(4-7.25) post-operation.The results of univariate analysis showed statistically significant inter-group differences in operative duration[(574.43±80.53)min vs.(526.75±72.42)min], intraoperative blood loss[400(300, 550)ml vs.320(300, 400)ml], red blood cell transfusion[2(2, 3)U vs.2(1.5, 2.0)U], preoperative platelet count[178.5(141.75, 242.5)×10 9/L vs.257 (209.75, 357)×10 9/L], postoperative infection rate[27.8%(25/90)vs.13.9%(10/72)] and dosing rates of piperacillin sodium and tazobactam sodium[8.9%(8/90)vs.25.0%(18/72)] ( P<0.05). Multivariate Logistic regression analysis revealed statistically significant inter-group differences in operative duration( P=0.008), red blood cell transfusion( P=0.01), preoperative platelet count( P<0.01) and postoperative infection rate ( P=0.02). The results of ROC curve analysis showed that the cut-off values of operative duration, red blood cell transfusion and preoperative platelet count were 535 min, 2.75 U and 183.5×10 9/L respectively.Length of ICU stay was higher in TCP group than that in non-TCP group, and the difference was statistically significant [4(3, 5) vs.3(3, 4) day, P=0.006]. Conclusions:LT children aged under 4 years with intraoperative red blood cell transfusion>2.75 U, operative duration>535 min and preoperative platelet count<183.5×10 9/L are more likely to develop post-transplantation TCP.And occurrence of TCP prolongs the length of ICU stay in pediatric recipients.

ObjectiveTo evaluate the efficacy and safety of topical Bisaitong （鼻塞通） in treating moderate-to-severe allergic rhinitis （AR）. MethodsA randomized， positive-controlled， non-inferiority clinical trial design was adopted. Totally， 108 cases of moderate-to-severe AR were randomly divided into Bisaitong group and mometasone furoate group，with 54 cases in each group. The Bisaitong group was treated with Bisaitong smeared at the nasal cavity twice a day， and the mometasone furoate group received inhalation of mometasone furoate nasal spray 100 μg in each nostril， once a day. Both groups were treated for 4 weeks and followed up after additional 4 weeks. Both groups were compared on the rhinoconjunctivitis quality of life questionnaire （RQLQ）， rhinoconjunctivitis total symptom score （RTSS）， visual analogue score （VAS） of sneezing， runny nose， nasal itching， nasal congestion degree， days of AR episodes at enrollment， after 2- and 4-week， and at follow-up. The peripheral blood eosinophil （EOS） count and percentage （EOS%）， serum eosinophil cationic protein （ECP）， serum dust mite， dermatophagoides farinae， and cockroach allergen-specific IgE （sIgE） levels were compared between groups at enrollment and after 4-week treatment. Drug overuse rate was calculated， and the safety was evaluated. The analysis of all efficacy outcomes was based on both full analysis set （FAS） and per-protocol set （PPS）. ResultsThe lower limit of the 95% confidence interval for the differences in RQLQ scores were greater than -0.6 measured after 2- and 4-week treatment and at follow-up compared to that measured at the enrollment in both groups， indicating of the Bisaitong group being non-inferior to the mometasone furoate group. There was no statistically significant difference between groups on RTSS score， VAS scores of sneezing， runny nose， nasal itching， nasal congestion degree and days of episodes at all timepoints （P＞0.05）， but each outcome changed significantly over time in both groups （P＜0.01）. The differences between groups in EOS count， EOS%， ECP levels， serum dust mite， dermatophagoides farinae， cockroach sIgE levels， and drug overuse rate were not statistically significant at enrollment and after 4-week treatment （P＞0.05）. Adverse events occurred in eight cases （15.10%） in the Bisaitong group and five cases （9.30%） in the mometasone furoate group， showing no significant difference between groups （P＞0.05）. ConclusionTopical Bisaitong is non-inferior to mometasone furoate nasal spray in the treatment of moderate to severe AR in terms of clinical symptom relief，reduction in the episodes， improvement of quality of life， and sound safety.

Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Depressive Disorder, Major/metabolism* ; Basal Forebrain ; Depression ; Hippocampus/metabolism* ; Cholinergic Agents

OBJECTIVE To explore the role of Th1/Th2 immune balance in the signal transduction of H1R, PAR-2/TRPV1 itch signal pathway and the intervention mechanism of Fuxian lotion. METHODS There were 60 BALB/c mice randomly divided into 6 groups after 3 days of adaptive feeding, with 10 mice in each group, which were blank control group, model control group, high, medium and low dose group of Fuxian lotion(36, 12, 4 mg·cm-2) and positive drug control group(1 mg·cm-2). Except for the blank control group, all other groups were sensitized with 7% and 0.5% 2,4-dinitrochlorobenzene acetone olive oil solution for multiple times. The abdomen and ears of mice in the blank group were coated with acetone solution for control. The drug was administered 24 hours after challenge, twice a day for 10 consecutive days. The ear thickness and the degree of mice ear swelling were measured and scored. The times of scratching the ears of mice were counted. The spleen index was calculated. HE staining was used to observe the pathological changes in mice ear tissue. The serum TNF-α, IL-1β, IL-31 levels were detected by ELISA, the mRNA level of the above immune factors was detected by realtime PCR, and the expression of H1R, PAR-2 and TRPV1 was detected by immunohistochemistry. RESULTS Compared with the blank control group, the ear thickness, ear allergic reaction score, scratching index, the spleen index of mice in the model control group was significantly increased(P<0.01), the TNF-α, IL-1β, IL-31 protein level and mRNA level were significantly increased(P<0.01), and the contents of H1R, PAR-2 and TRPV1 were significantly increased(P<0.01). There were obvious eczema like pathological changes in chronic dermatitis. Compared with the model control group, Fuxian lotion could effectively reduce the degree of auricle swelling, the score of ear allergic reaction, scratch index and spleen index, significantly reduce the levels of TNF-α, IL-1β, IL-31 protein level and mRNA level(P<0.01). The content of H1R in the high dose group of Fuxian lotion, the medium dose group of Fuxian lotion and the positive drug control group was significantly reduced(P<0.01), and the content of PAR-2 and TRPV1 in all dose groups of Fuxian lotion and the positive drug control group were significantly reduced(P<0.01). CONCLUSION Fuxian lotion can improve chronic dermatitis and eczema by regulating the Th1/Th2 immune balance, down regulating the characteristic immune factor TNF-α, IL-1β, IL-31 and interfering with the itch signal pathway H1R, PAR-2/TRPV1 transmission, so as to anti-itching and inhibit inflammatory response.

The improvement of survival of osteosarcoma patients by the standard treatment strategy of osteosarcoma(neoadjuvant chemotherapy+surgical treatment+adjuvant chemotherapy)has been stabilized in the past 20 years,and the emergence of the slow(controlled)-release drug delivery system has provided a new strategy for the treatment of osteosarcoma.At present,thanks to the development of nanotechnology,great progress had been made to the technology of slow-release chemotherapy for osteosarcoma in China,but the clinical translation of the slow-release chemotherapy system has become the key to constrain its development.Based on this,this review summarizes the preclinical research progress of the main chemotherapeutic agents for osteosarcoma,including methotrexate,doxorubicin,cisplatin,and isocyclophosphamide,in the recent years,with the expectation of clarifying the safety and efficacy of the slow-release chemotherapy system for osteosarcoma,and facilitating the clinical translation of the slow-release chemotherapy system for osteosarcoma.

Germany owns the largest herbal market in Europe and has the world's leading R&D capabilities for herbal medicine products. Chinese herbal medicine (CHM) spreaded to Germany hundreds of years ago. Since the beginning of the 20th century, China and Germany have signed a series of agreements to support traditional medicine cooperation, and the exchange of herbs between China and Germany has become more frequent, bringing opportunities for CHM to enter into Germany. In recent years, China and Germany have gained progress in the fields of CHM research and trade, etc. However, there are differences in the understanding of herbal medicines, quality standard evaluation, usage, and medication rules between the two countries. By doing SWOT analysis of the development of CHM in Germany, this paper suggested to promote Sino-German medical exchanges and build a community of common health for mankind through strengthening the clinical application of CHM, finding new ways of CHM entering into German market, and building an international talent team of traditional Chinese medicine.

Objective:To analyze the diagnostic value of X-ray, CT and MRI multimodal images in the vertebral compression fractures caused by osteolytic metastases and osteoporosis.Methods:The basic clinical data and X-ray, CT, MRI imaging data of 102 patients with vertebral compression fractures from January 2019 to May 2021 in Jiangnan Hospital (Xiaoshan Traditional Chinese Medicine) Affiliated to Zhejiang University of Traditional Chinese Medicine were retrospectively analyzed. Among them, vertebral compression fractures caused by osteolytic metastases was in 47 cases, and vertebral compression fractures caused by osteoporosis was in 55 cases.Results:The age and osteoporosis rate in patients with vertebral compression fractures caused by osteolytic metastases were significantly lower than those in patients with vertebral compression fractures caused by osteoporosis: (61.95 ± 11.84) years old vs. (72.37 ± 12.55) years old and 4.3% (2/47) vs. 83.6% (46/55), the body mass index and pain visual analogue score were significantly higher than those in patients with vertebral compression fractures caused by osteoporosis: (22.58 ± 3.85) kg/m 2 vs. (18.11 ± 2.79) kg/m 2 and (8.31 ± 2.91) scores vs. (7.02 ± 2.72) scores, and there were statistical differences ( P<0.05); there was no statistical difference in gender composition ( P>0.05). The rates of vertebral body wedge shape and double concave shape in patients with vertebral compression fractures caused by osteolytic metastases were significantly lower than those in patients with vertebral compression fractures caused by osteoporosis: 2.80% (3/107) vs. 60.82% (104/171) and 6.54% (7/107) vs. 29.82% (51/171), the rates of flat shape and posterior margin swelling were significantly higher than those in patients with vertebral compression fractures caused by osteoporosis: 75.70% (81/107) vs. 9.36% (16/171) and 14.95% (16/107) vs. 0, and there were statistical differences ( P<0.01); the rates of pedicle involvement and soft tissue mass in patients with vertebral compression fractures caused by osteolytic metastases were significantly higher than those in patients with vertebral compression fractures caused by osteoporosis: 68.09% (32/47) vs. 1.82% (1/55) and 46.81% (22/47) vs. 0, while the rate of linear image signal in vertebral body was significantly lower than that in patients with vertebral compression fractures caused by osteoporosis: 0 vs. 96.36% (53/47), and there were statistical difference ( P<0.01); there was statistical difference in MRI signals ( P<0.01), vertebral compression fractures caused by osteolytic metastases were mainly characterized by low T 1 high T 2 and low T 1 low T 2, while vertebral compression fractures caused by osteoporosis was mainly characterized by low T 1 high T 2; the rates of disc compression and widening in patients with vertebral compression fractures caused by osteolytic metastases were significantly lower than those in patients with vertebral compression fractures caused by osteoporosis: 4.26%(2/47) vs. 34.55% (19/55) and 2.13%(1/47) vs. 18.18% (10/55), and there were statistical differences ( P<0.01 or <0.05). The accuracies of multimodal imaging in the diagnosis of vertebral compression fractures caused by osteolytic metastases and osteoporosis were significantly higher than those of X-ray, CT and MRI (89.4% vs. 51.1%, 72.3%, 83.0%; 90.9% vs. 52.7%, 60.0%, 78.2%), and there were statistical differences( P<0.05). Conclusions:Multimodal imaging is helpful to improve the diagnostic accuracy of vertebral compression fractures caused by osteolytic metastases and osteoporosis, to reduce the clinical misdiagnosis rate, with important reference value for the differential diagnosis of the two diseases.

The association of Zika virus (ZIKV) infection with microcephaly has raised alarm worldwide. Their causal link has been confirmed in different animal models infected by ZIKV. However, the molecular mechanisms underlying ZIKV pathogenesis are far from clear. Hence, we performed global gene expression analysis of ZIKV-infected mouse brains to unveil the biolog-ical and molecular networks underpinning microcephaly. We found significant dysregulation of the sub-networks associated with brain development, immune response, cell death, microglial cell acti-vation, and autophagy amongst others. We provided detailed analysis of the related complicated gene networks and the links between them. Additionally, we analyzed the signaling pathways that were likely to be involved. This report provides systemic insights into not only the pathogenesis, but also a path to the development of prophylactic and therapeutic strategies against ZIKV infection.