Wnt5a up-regulates Periostin through CaMKII pathway to influence periodontal tissue destruction in early periodontitis.

Periostin is essential for periodontal tissue integrity and homeostasis and also associated with periodontitis and periodontitis healing. This study aims to investigate the temporal and spatial expression of Periostin and Wnt5a/CaMKII in periodontitis and how the Wnt5a regulates Periostin through CaMKII signaling pathway in PDLCs in inflammatory environment. The experimental periodontitis mice were adopted to clarify the temporal and spatial expression of Wnt5a, CaMKII and Periostin during early periodontitis. And the Wnt5a, CaMKII and Periostin expression pattern and regulation mechanism in PDLCs were clarified in Porphyromonas gingivalis Lipopolysaccharide (P.g. LPS) induced inflammatory condition. Along with the periodontitis development, Wnt5a, CaMKII and Periostin significantly increased in periodontal ligament and partially increased in gingiva during 0 to 6 day (P < 0.05). They were involved in early periodontitis homeostasis especially in periodontal ligament tissue. Meanwhile, Wnt5a, CaMKII and Periostin were significantly decreased at 12 h (P < 0.05) and increased at 48 h (P < 0.05) in PDLCs after induced by P.g. LPS. Besides, Wnt5a significantly enhanced total CaMKII protein (P < 0.05), pCaMKII (P < 0.001) and Periostin (P < 0.001), and this could be blocked by CaMKII inhibitor KN93 (P < 0.05). In conclusions, in early periodontitis, Wnt5a/CaMKII and Periostin should be involved in maintaining periodontal homeostasis and Wnt5a could up-regulate Periostin via CaMKII pathway in inflammation, which would provide new clues for us to understand the pathogenesis of periodontitis and develop better therapeutic strategies.

Antibody landscape against SARS-CoV-2 proteome revealed significant differences between non-structural/ accessory proteins and structural proteins

The immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N protein before death was observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology. HighlightsO_LIAn antibody response landscape against SARS-CoV-2 proteome was constructed C_LIO_LINon-structural/accessory proteins elicit prevalent antibody responses but likely through a different mechanism to that of structural proteins C_LIO_LIIgG antibodies against non-structural/accessory proteins are more associated with disease severity and clinical outcome C_LIO_LIFor non-survivors, the levels of IgG antibodies against S1 and N decline significantly before death C_LI

Antibody dynamics to SARS-CoV-2 in Asymptomatic and Mild COVID-19 patients

ImportanceAsymptomatic COVID-19 infections have a long duration of viral shedding and contribute substantially to disease transmission. However, the missing asymptomatic cases have been significantly overlooked because of imperfect sensitivity of nucleic acid testing. We aimed to investigate the humoral immunity in asymptomatics, which will help us develop serological tests and improve early identification, understand the humoral immunity to COVID-19, and provide more rational control strategies for the pandemic. ObjectiveTo better control the pandemic of COVID-19, dynamics of IgM and IgG responses to 23 proteins of SARS-CoV-2 and neutralizing antibody in asymptomatic COVID-19 infections after exposure time were investigated. Design, setting, and participants63 asymptomatic individuals were screened by RT-qPCR and ELISA for IgM and IgG from 11,776 personnel returning to work, and close contacts with the confirmed cases in different communities of Wuhan by investigation of clusters and tracing infectious sources. 63 healthy contacts with both negative results for NAT and antibodies were selected as negative controls. 51 mild patients without any preexisting conditions were also screened as controls from 1056 patients during hospitalization in Tongji Hospital. A total of 177 participants were enrolled in this study and serial serum samples (n=213) were collected. The research was conducted between 17 February 2020 and 28 April 2020. Serum IgM and IgG profiles of 177 participants were further probed using a SARS-CoV-2 proteome microarray. Neutralizing antibody responses in different population were detected by a pseudotyped virus neutralization assay system. The dynamics of IgM and IgG antibodies and neutralizing antibodies were analyzed with exposure time or symptoms onset. ResultsAsymptomatics were classified into four subgroups based on NAT and serological tests. In particular, only 19% had positive NAT results while approximately 81% detected positive IgM/IgG responses. Comparative SARS-CoV-2 proteome microarray further demonstrated that there was a significantly difference of antibody dynamics responding to S1 or N proteins among three populations, although IgM and IgG profiles could not be used to differentiate them. S1 specific IgM responses were elicited in asymptomatic individuals as early to the seventh day after exposure and peaked on days from 17d to 25d, which might be used as an early diagnostic biomarker and give an additional 36.5% seropositivity. Mild patients produced stronger both S1 specific IgM and neutralizing antibody responses than asymptomatic individuals. Most importantly, S1 specific IgM/IgG responses and the titers of neutralizing antibody in asymptomatic individuals gradually vanished in two months. Conclusions and relevanceOur findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health and immunization strategies.

Preparation and Quality Evaluation of Pogostone Transfersomes / 中国药房

OBJECTIVE： To prepare pogostone transfersomes， and to evaluate its quality. METHODS： Film dispersion method was used to prepare pogostone transfersomes. Using the accumulative penetration volume （Qn） and accumulative penetration ratio （PR） of pogostone as evaluation indexes， the types of surfactant， formulation were screened in respects of the dosage of surfactant and the dosage of pogostone. The pogostone transfersomes were prepared with optimal formulation； the morphology， particle size distribution and Zeta potential were observed and the entrapment efficiency was measured. RESULTS： The optimal formulation was as follows as the sodium cholate was selected as surfactant； the dosage of sodium cholate was 0.25 g； the dosage of pogostone was 15 mg. The optimal pogostone transfersomes were ivory-white suspension； average particle size was （115.6±3.65） nm （RSD＝3.20％，n＝3）； PDI was 0.185±0.008 （RSD＝4.30％， n＝3）； Zeta potential was （－13.76±0.225） mV （RSD＝1.70％，n＝3）； entrapment efficiency of pogostone was （46.01±0.40）％ （RSD＝0.87％，n＝3）； Qn was （378.76±0.61）   μg/cm2 （RSD＝0.20％，n＝3）； PR was （89.02±0.96）％ （RSD＝1.10％，n＝3）. CONCLUSIONS： Prepared pogostone transfersomes are in line with quality requirements， which can provide reference for the further study of new dosage form of pogostone.

Combined treatment of perianal condyloma acuminatum inHIV seropositive men who have sex with men with microwave and photo-dynamic therapy / 中华实验和临床病毒学杂志

Objective@#To analyze the clinical features of perianal condyloma acuminatum in HIV infected men who have sex with men (MSM) and assess the effects of combined treatment of microwave and photodynamic therapy.@*Methods@#Clinical and laboratory data of 260 male patients with perianal condyloma acuminatum were collected and microwave combined with photodynamic therapy was applied on them.@*Results@#The majority of the patients with perianal condyloma acuminatum were young people (243/260). Warts were mainly located in the anus or from the outside to inside of the anus (245/260). Among them, the proportion of warts position of extraanal in HIV-infected group (8/220) was lower than that of non-HIV-infected group (7/40). HPV types 11 (70/118), 6 (44/118) and 16 (40/118) were the most common types of HPV infection. People with HIV infection were more likely to develop high-risk, mixed types HPV infection and multiple HPV infection than those without HIV infection. More than half of the patients (146/260) needed only 1-3 sessions of photodynamic treatments. There was no significant difference in the times of photodynamic treatments and the numbers of photosensitizers required between the HIV-infected and non-HIV-infected groups. The recurrence rate of HIV-infected group (13.6%, 30/220) was also similar to that of non-HIV-infected group (15.0%, 6/40), but far lower than those who underwent microwave therapy alone (45%, 18/40).@*Conclusions@#The combination therapy significantly reduced the recurrence rate of perianal condyloma acuminatum in HIV infected MSM.

Analgesia,Sedation Effects and Safety of Flurbiprofen Axetil Combined with Hydromorphone for PCIA after Orthopedics Surgery / 中国药房

OBJECTIVE:To observe analgesia,sedation effects and safety of flurbiprofen axetil combined with hydromorphone for postoperative patient-controlled intravenous analgesia (PCIA) after orthopedics surgery. METHODS:Totally 90 patients with combined spinal epidural anesthesia underwent lower limb surgery were selected from anesthesology department in the Affiliated Hospital of Chengde Medical College during May 2016-Jan. 2018. They were divided into SF group,H group and KH group according random number table,with 30 cases in each group. The postoperative PCIA pump drug liquid formula of SF group included Sufentanil citrate injection 2-3 μ g/kg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL;that of H group included Hydromorphone hydrochloride injection 0.12 mg/kg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL;that of KH group included Hydromorphone hydrochloride injection 0.12 mg/kg+Flurbiprofen axetil injection 50 mg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL. The operation time, intraoperative medication (epidural application frequency of additional ropivacaine,frequency of ephedrine and atropine),effective pressing times of analgesic pump and the analgesic effect of PCIA were observed in 3 groups. VAS score and Ramsay sedation score were observed 2,6,12,24,48 h after surgery. The hospital anxiety and depression scale (HAD) score,profile of mood states (POMS) score and the occurrence of ADR were observed before and after surgery. RESULTS:There was no statistical significance in operation time,epidural application frequency of additional ropivacaine or frequency of ephedrine and atropine among 3 groups (P＞0.05). The effective pressing times of analgesic pump in KH group were significantly lower than SF group and H group. The proportion of patients with excellent and good anesthesia effect in KH group was significantly higher than SF group and H group (P＜0.05);there was no statistical significance between SF group and H group(P＞0.05). VAS score of 3 groups 48 h after surgery were significantly lower than 6, 12,24 h after surgery;that of KH group was significantly lower than SF group and H group(P＜0.05);there was no statistical significance between SF group and H group(P＞0.05). There was no statistical significance in Ramsay score among 3 groups at different time points(P＞0.05). Before surgery,there was no statistical significance in HAD score or POMS score among 3 groups (P＞0.05). After surgery,HAD score and POMS score of KH group and H group were significantly lower than before surgery and SF group(P＜0.05);there was no statistical significance in KH group and H group,before and after surgery in SF group(P＞0.05). No vomiting,respiratory depression,pruritus and digestive tract bleeding were observed in 3 groups. The incidence of dizziness and nausea in H group and KH group were significantly lower than SF group (P＜0.05);there was no statistical significance between KH group and H group(P＞0.05). CONCLUSIONS:The flurbiprofen axetil combined with hydromorphone show good analgesic and sedative effect for PCIA after orthopedics operation,and can significantly improve emotion and mood of patients with good safety.

[Research progression of the relationship between integrin α2ß1 and drug-induced gingival overgrowth].

Drug-induced gingival overgrowth (DIGO) is characterized by fibrous gingival hyperplasia and increased gingival volume. DIGO is histologically associated with proliferation of cells and deposition of extracellular matrices, particularly collagen. Integrin α2ß1 is related to collagen phagocytosis and involved in the occurrence and progression of DIGO. This paper reviews the progress of research on the relationship between integrin α2ß1 and DIGO.

Research progression of the relationship between integrin α2β1 and drug-induced gingival overgrowth / 华西口腔医学杂志

Drug-induced gingival overgrowth (DIGO) is characterized by fibrous gingival hyperplasia and increased gingival volume. DIGO is histologically associated with proliferation of cells and deposition of extracellular matrices, particularly collagen. Integrin α2β1 is related to collagen phagocytosis and involved in the occurrence and progression of DIGO. This paper reviews the progress of research on the relationship between integrin α2β1 and DIGO.