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Introduction: Long‐term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression. Aims: This study aimed to identify changes in hippocampus synaptic plasticity under LSCS. Methods: The present study simulated the real long‐term space station environment by conducting a 42‐day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch‐clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting. Results: The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel. Conclusion: These results suggested that LSCS‐induced depressive behaviors by impairing synaptic plasticity in rat hippocampus. [ABSTRACT FROM AUTHOR]

The mechanism of Rehmanniae Radix Praeparata against osteoarthritis was investigated based on network pharmacology, molecular docking, and in vitro experiments in the present study. Osteoclast models were established via receptor activator of nuclear factor-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) inducing RAW264.7 cells. Further, the influence of Rehmanniae Radix Praeparata on the activity of tartrate-resistant acid phosphatase(TRAP) was evaluated and the efficacy of Rehmanniae Radix Praeparata in the treatment of osteoarthritis was verified. The active components of Rehmanniae Radix Praeparata were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and literature, and the potential targets of the components were collected from SwissTargetPrediction. Osteoarthritis disease targets were searched in Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), GeneCards, and DisGeNET. The intersection targets of Rehmanniae Radix Praeparata and osteoarthritis were obtained by Venny platform. The protein-protein interaction(PPI) network was constructed by Cytoscape 3.8.2, and key targets were obtained based on topology algorithm. The Database for Annotation, Visualization and Integrated Discovery(DAVID) was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally, the mRNA expression of the key targets was determined by RT-qPCR and the binding activity between the components and key targets was validated by molecular docking. The results showed that Rehmanniae Radix Prae-parata inhibited the TRAP activity, thus inhibiting bone resorption by osteoclasts and treating osteoarthritis. By network pharmacology, 14 active components of Rehmanniae Radix Praeparata and 126 intersection targets were obtained. The network pharmacology enrichment results revealed 432 biological processes and 139 signaling pathways. Key targets such as proto-oncogene tyrosine-protein kinase Src(SRC), signal transducer and activator of transcription 3(STAT3) and transcription factor p65(RELA) were obtained according to the degree in topological analysis. SRC was highly expressed in osteoclasts, which accelerated the development of osteoarthritis. Therefore, SRC was selected for subsequent verification, and Rehmanniae Radix Praeparata decreased the gene expression level of SRC. The molecular docking showed that acteoside, isoacteoside, raffinose had good bonding activity with SRC, suggesting that they might be the critical components in treating osteoarthritis. In conclusion, Rehmanniae Radix Praeparata can inhibit bone resorption by osteoclasts and balance the metabolism of articular cartilage and subchondral bone via acting on SRC, thus playing a therapeutic role in osteoarthritis. In addition, Rehmanniae Radix Praeparata may exert overall efficacy on osteoarthritis through other targets such as STAT3 and RELA, and other related pathways such as PI3 K-AKT and IL-17 signaling pathways.

Objective: To investigate the differential plasma protein profiles in patients with hyperlipidemia & atherosclerosis (H&A) of different patterns of phlegm-stasis syndrome (PSS) for seeking their biomarker proteins., Methods: Two-dimensional gel electrophoresis and gel screening graphical analysis were performed on plasma proteins got from 146 patients; corresponding protein spots were fetched from the gel for two-stage mass-spectrometric analysis by quadruple time-of-flight mass spectrometry; then the differential proteins for PSS were discriminated by Fisher discriminate analysis., Results: Excepting two uncertain proteins, 7 differential proteins were screened out from the 11 differentially expressed plasma protein spots with variability over 100% in the inter-block matching. Classic analysis found that haptoglobin precursor and fibrinogen gamma chain were possibly the plasma biomarker proteins for H & A; fibrinogen beta chain and apolipoprotein A-I precursor were that set apart PSS from non-PSS; fibrinogen gamma chain, albumin and apolipoprotein A-I precursor were for phlegm syndrome; haptoglobin precursor, adrenomedullin binding protein precursor, albumin and complement component C4 were for stasis syndrome; albumin and adrenomedullin binding protein precursor were for the phlegm-stasis mutual blocking syndrome. Moreover, the above mentioned expressions of possible marker proteins had their own special rule of changing in the transforming progress of PSS., Conclusion: This study reported, for the first time, the existence of evident variation of functional protein constitution in different patterns of PSS, and definite compatibility being detected in some functional proteins, which may be the marker proteins for making diagnosis and prognosis of PSS in H&A. Besides, preliminary proof for the transformation of PSS has gained at the functional protein level.

Objective: To investigate the relationship between the plasma biomarker proteins and the states of Zang-Fu organs in patients with phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis., Methods: The states of Zang-Fu organs in 146 patients with hyperlipidemia and atherosclerosis were diagnosed by syndrome differentiation of traditional Chinese medicine. The plasma proteins from these patients were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE). Differential protein profiling was established by Image Master 6.0 software, and the differential proteins were analyzed by quadrupole time of flight mass spectrometry (Q-TOF-MS). The association between the plasma biomarker proteins and the states of Zang-Fu organs was analyzed by graphical models., Results: The biomarker proteins such as fibrinogen gamma chain, albumin and apolipoprotein AI (precursor) in discrimination of the patients with phlegm syndrome from phlegm accumulating with stagnation syndrome were correlated with the deficiency of kidney-qi, heart-qi and spleen-qi. Among the four biomarker proteins in discrimination of the patients with phlegm syndrome from blood stagnation syndrome, albumin, adrenomedullin binding protein (precursor) and haptoglobin (precursor) were correlated with the deficiency of kidney-qi and heart-qi, but complement component C4 was independent of the deficient Zang-Fu organs. The biomarker albumin was associated with the deficiency of kidney-qi, heart-qi and spleen-qi, and adrenomedullin binding protein (precursor) was correlated with the deficiency of spleen-qi in discrimination of the patients with blood stagnation syndrome from phlegm accumulating with stagnation syndrome. As the potential biomarker proteins in discrimination of the patients with non-phlegm and non-stagnation syndrome from phlegm accumulating with stagnation syndrome, the fibrinogen beta chain was related with the deficiency of kidney-qi, and apolipoprotein AI (precursor) was correlated with both the deficiency of kidney-qi and heart-qi., Conclusion: There exists inherent correlation between the states of Zang-Fu organs and the plasma probable biomarker proteins in the patients with different phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis.

To detect HPV in genital warts (Condylomata acuminata, CA) for infection rate and association of specific HPV types between males and females, and to provide support for the development of HPV vaccines, we designed HPV type-specific oligonucleotide primers to amplify DNA fragments encoding L1 viral capsule protein. SSP-PCR was conducted in duplication for each CA sample from male and female patients. DNA of TA-cloned HPV was used as positive control, and deionized H2O was used as negative control. A total of 22 clinical samples, 13 from males and 9 from females, was collected from patients diagnosed with CA at hospitals in Beijing and Handan. HPV viral DNA was amplified in all 22 samples analyzed, with 100% detection rate. TA-cloning and sequencing of the PCR products confirmed correct amplification of HPV type-specific fragments. Of the 13 samples from males, 5 were infected with HPV6, 6 with HPV11, and 2 with HPV6 + HPV11. Of the 9 samples from females, 3 were infected with HPV6, 2 with HPV11, and 4 with both HPV6 and HPV11 infection. In addition, high-risk types HPV16, HPV18, HPV33, HPV35, HPV45, HPV54, HPV56 and HPV58 were also detected in 4 female samples that were mixed with cervical cell debris during sample collection. However, no HPV types other than HPV6 and HPV11was detected in all CA-only samples in this study. We have established a sensitive and reliable laboratory procedure for HPV detection and classification. Using the method, we reached 100% detection rate of HPV in the CA samples. Our results confirm that HPV6 and HPV11 are primarily responsible for CA, and there is no specific association of HPV types between warts in males and females.

Objective: To study the relationship between human herpesvirus 6 (HHV-6) and oral squamous cell carcinoma., Methods: The serum anti-HHV-6 antibody titers from oral squamous cell carcinoma patients and control subjects were detected by indirect immunofluorescence assay. HHV-6 DNA in peripheral blood mononuclear cells from oral squamous cell carcinoma patients and control subjects was amplified by PCR with primers from sequence of HHV-6 and the specificity was confirmed by Southern-blot hybridization with an internal probe oligonucleotide. An immunohistochemical staining using rabbit anti-HHV-6 antibody was used to detect HHV-6 antigen in oral tumor tissues from oral squamous cell carcinoma patients., Results: Significantly higher proportion of patients with oral carcinoma (16/16) had IgG antibody to HHV-6 in sera compared with those (12/16) in control subjects, and geometric mean titer of these two groups was 1:118 and 1:64 respectively (P less than 0.05). The detectable rate of HHV-6 DNA in peripheral blood mononuclear cells for the above groups was 10/16 and 6/16 respectively (P less than 0.05). HHV-6 antigens were positive in 9 out of 12 oral tumor cases and in only 2 out of 8 pericancerous tissues the difference between these two groups was also significant (P less than 0.05)., Conclusion: These results demonstrated the frequent presence of HHV-6 in oral squamous cell carcinoma, therefore, HHV-6 possibly play a role in the pathogenesis of oral squamous cell carcinoma.

Aim: To establish an indirect immunofluorescence assay(IFA) for detection of serum IgG antibody against human herpesvirus 6(HHV-6)., Methods: Cord blood mononuclear cells infected by HHV-6 strain CN(5) were used to prepare cell antigen smear, so as to establish an IFA and make an epidemical investigation on serum specimens of child-bearing age, women., Results: The specificity of the IFA for HHV-6 was confirmed by absorption assay(test). The IFA detection showed that in serum specimens from 116 cases of child-bearing age, women, the positive rate of anti-HHV-6 IgG was 72.4% and geometric mean titer(GMT) was 1:61. The positive rate and GMT of serum anti-HHV-6 IgG had no differences between pregnant women and unpregnant women, neither among pregnant women at different pregnant stages., Conclusion: A specific IFA has been developed successfully for epidemical investigation of HHV-6 infection rate in child-bearing women.