OBJECTIVE To explore the effect and mechanism of warming channels and activating blood circulation external treat-ment to alleviate peripheral hyperalgesia in knee osteoarthritis(KOA)based on NGF/TrKA signaling pathway.METHODS 30 SD rats were randomly divided into normal group,KOA group and Yiceng group.KOA model was established by anterior cruciate ligament transection(ACLT).14 days after model establishment,rats in Yiceng group were treated with Yiceng patch.The peripheral pain threshold of rats was measured at different time points.The cartilage sections were stained with HE,Aggrecan and type II collagen.The synovial sections were stained with HE,Sirius red,silver and performed with immunostaining.The protein expression of key molecules NGF and TrKA of NGF/TrKA signaling pathway,inflammatory index IL-1β,pain mediator TRPV1,pan-neural mark-ers PGP9.5 and S100 in synovium and complexes transported to dorsal root ganglia(DRG)tissues via nerve endings was determined by Western Blot.The corresponding gene expression was determined by qPCR.The levels of NGF and SP in peripheral blood of rats were determined by ELISA.RESULTS Compared with the KOA group,the cold allodynia and mechanical allodynia thresholds of the rats in the Yiceng group increased(P<0.05,P<0.01);the protein and gene expression of NGF,TrKA,TRPV1,IL-1β,PGP9.5 in the synovial tissue decreased(P<0.05,P<0.01);the protein and gene expression levels of TRPV1,PGP9.5,S100 in the DRG tissue were downregulated(P<0.05,P<0.01).CONCLUSION The warming channels and activating blood circulation external treatment can inhibit the NGF/TrKA signaling pathway,downregulate the gene and protein expressions of NGF,TrKA,TRPV1,IL-1β,PGP9.5,and may inhibit the sprouting of sensory nerve fibers and improve the peripheral hyperalgesia state of rats with KOA.

Percutaneous dilatational tracheostomy (PDT) is a surgical method for quickly establishing an artificial airway, which has been favored by clinicians because of its simple operation, small trauma and bedside operation. However, for patients with tracheal intubation in intensive care unit (ICU), the tip and balloon of the existing endotracheal tube will not only hinder percutaneous puncture, but also hinder insertion of guidewire and tracheotomy tube, and consequently affect the process of PDT. On the contrary, blind withdrawal of the existing endotracheal tube may cause the tracheal tube tipleave the glottis, leading to an emergency airway situation that endangers the patient's life. Therefore, the medical staff from intensive care medicine department of the First People's Hospital of Chenzhou designed a laryngeal mask and its monitoring device, which is convenient for withdrawal of endotracheal tube, and obtained the national utility model patent of China (patent number: ZL 2020 2 2795887.1). The device is composed of a laryngeal mask and a monitoring device. The laryngeal mask mainly includes a laryngeal mask body, a vent tube, a guidance tube and other components. The laryngeal mask body is mainly used to seal the throat and provide the air supply channel for the patient together with the ventilation tube. The main function of the guidance tube is to accommodate the tracheal tube and facilitate the withdrawal of the inserted tracheal tube. During percutaneous dilatation tracheotomy, this device can monitor the withdrawal of tracheal catheter in real time, and immediately ensure the airway patency of patients without re-intubation when the cuff of tracheal catheter exits the glottis. The utility model has the advantages of real-time monitoring, simple operation, safety and convenience, and is worthy of transformation and promotion.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To evaluate the effect of esketamine on postoperative acute lung injury (ALI) in pediatric patients undergoing living donor liver transplantation.Methods:Sixty pediatric patients of either sex with biliary atresia, aged 0-36 months, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, with cardiac function grade I or Ⅱ, with Child-Pugh grade B or C, undergoing living donor liver transplantation, were divided into 2 groups ( n=30 each) using a computer-generated table of random numbers: control group (group C) and esketamine group (group S). Combined intravenous-inhalational anesthesia was performed with propofol and sevoflurane in both groups, and in addition esketamine was intravenously infused continuously after induction in group S. After anesthesia induction (T 0), at 60 min after start of surgery (T 1), at 10 min after anhepatic phase (T 2), at 60 min after portal vein opening (T 3), and immediately after abdominal closure (T 4), central venous blood samples were collected for determination of the serum concentrations of Clara cell secretory protein 16, surface active protein D, soluble receptor for advanced glycation end-products, high mobility group protein B1, interleukin-1beta and tumor necrosis factor-alpha (using enzyme-linked immunosorbent assay), concentrations of malondialdehyde (using TBA method), and activity of superoxide dismutase (using hydroxylamine method). The dynamic lung compliance was recorded from T 0 to T 4. Blood samples were taken from the radial artery at T 0 and 24 h after surgery (T 5) for blood gas analysis, and oxygenation index and respiratory index were calculated. Lung ultrasound scores were recorded at 24 h before surgery and T 5. The postoperative mechanical ventilation time and duration of intensive care unit stay were recorded. The occurrence of ALI within 7 days after liver transplantation was observed. Results:Compared with group C, the serum concentrations of Clara cell secretory protein 16, surface active protein D, soluble receptor for advanced glycation end products, high mobility group protein B1, interleukin-1beta, tumor necrosis factor-alpha and malondialdehyde were significantly decreased, and the activity of superoxide dismutase was increased at T 3, 4, the oxygenation index was increased and respiratory index was decreased at T 3-T 5, lung ultrasound C score and B score were decreased at T 5, the postoperative mechanical ventilation time and duration of intensive care unit stay were shortened, and the incidence of ALI was decreased in group S ( P<0.05). Conclusions:Esketamine can alleviate postoperative ALI in pediatric patients undergoing living donor liver transplantation.

Objective:To investigate the efficacy of plasma exchange (PE) in treatment of patients with acute respiratory distress syndrome (ARDS).Methods:Forty-two patients who met the inclusion criteria in the intensive care unit of Chenzhou First People′s Hospital were randomly divided into control group and plasma exchange (PE) group with 21 cases in each group. The control group received conventional treatment; while the PE group received conventional treatment plus PE. The mechanical ventilation time (MVT), length of ICU stay (ICU LOS), 28-day mortality and 90-day mortality of patients were analyzed. The oxygenation index, SOFA score, norepinephrine (NE) dose, C-reactive protein (CRP), procalcitonin (PCT) and IL-6 levels were evaluated before and after treatment.Results:In the control group the oxygenation index, IL-6, PCT and CRP were significantly improved after treatment ( t=-4.50, 2.46, Z=-3.53, t=5.55, all P<0.05), but the SOFA score and NE dose were not significantly changed ( t=1.98, Z=-0.47,all P>0.05). In the PE group, the oxygenation index, SOFA score, IL-6, PCT, CRP were significantly improved and the NE dose was reduced after treatment ( t=2.18, 9.23, 5.26, Z=-3.77, t=7.27 and Z=-2.54,all P<0.05). The oxygenation index, SOFA score, IL-6, CRP were significantly better after treatment and NE dose was lower in PE group than those in the control group ( t=2.18, -2.21, -2.12, -2.61 and Z=-2.11, all P<0.05). Compared with the control group, the MVT(14.0±5.2d vs. 18.4±6.3d), ICU LOS(19.3±4.9d vs. 23.2±7.3d) and 28-day mortality (14.3%(3/21) vs. 42.8%(10/21)) in the PE group were significantly decreased ( t=-2.48, -2.04 and χ2=4.20,all P<0.05). There was no significant difference in the 90-d mortality between the two groups (28.6%(6/21) vs. 52.4%(11/21), χ2=2.47, P=0.208). Conclusion:Therapeutic plasma exchange can significantly reduce the inflammatory response, improve the organ function and reduce the short-term mortality of ARDS patients.

OBJECTIVE: To investigate the expression of citrullinated epitopes in articular cartilage protein and whether its expression is sufficient to induce anti-citrullinated protein antibody (ACPA) response in mice. METHODS: The experimental group was treated with different concentrations of lipopolysaccharide (LPS), heat-inactivated bacteria ( and ) or specific monoclonal antibody against type Ⅱ collagen to induce citrullination of articular cartilage protein, with PBS as the control. Immunohistochemistry with the monoclonal antibody ACC4 (IgG1) that specifically binds to the citrullinated epitope of cartilage protein was performed for detecting the expression of citrullinated protein, with ACC1 (IgG2a) as a positive control antibody and L243 (IgG2a) and Hy2.15 (IgG1) as the negative isotype control. In the in vivo experiment, SD rats were subjected to injection of different doses of LPS in the right knee (with PBS as the controls in the left knee), and 3 days later frozen sections were prepared for immunohistochemical detection of the expression of citrullinated protein. Models of collagen-induced arthritis (CIA) established in different mouse strains were observed for incidence and severity of CIA. Serum samples collected from these models and the sera from rheumatoid arthritis patients were examined for anti-citrullinated protein antibody, and immunohistochemistry was performed to detect the expression of citrullinated protein in the cartilage of the mouse. RESULTS: The citrullinated CII epitope-specific antibody ACC4 did not bind to articular cartilage tissues with different treatments as compared with the positive control antibody ACC1. The ACC4 antibody and the antibodies from patients with rheumatoid arthritis with high titers of anti-citrullinated protein antibody were capable of binding to the synovial tissue around the articular cartilage of the CIA. Luminex analysis showed that the anti-citrullinated protein antibody was lowly expressed in mouse serum, but the anti-type Ⅱ collagen triple helix structure peptide antibody exhibited strong reactivity. CONCLUSIONS Mild acute inflammatory response is not enough to cause citrullination of articular cartilage protein, and the expression of specific epitope requires a high-intensity inflammatory response. Inflammatory articular cartilage protein can express citrullinated epitopes in type Ⅱ collagen-induced arthritis in mice, but the expression of citrullinated epitopes is not sufficient to induce an immune response to anti-citrullinated antibodies. Stronger stimulation signals are required to induce an immune response for producing anti-citrullinated protein antibodies.
Animals ; Arthritis, Experimental ; Autoantibodies ; Cartilage, Articular ; Citrulline ; Humans ; Inflammation ; Mice ; Rats ; Rats, Sprague-Dawley

Objective: Computed tomography (CT)-guided percutaneous lung biopsy is difficult for small nodules and lesions that are adjacent to large blood vessels. This study investigated the validity of CT-guided percutaneous lung biopsy in the diagnosis of pulmo-nary nodules with a digital angle instrument. Methods: This study was a retrospective analysis of 35 patients with lung mass≤60 mm, who underwent CT-guided percutaneous lung biopsy from January 2018 to September 2018. Patients were assigned in to three groups. Group A and B were patients with pulmonary nodules≤30 mm. Biopsy of group A was performed with the help of a digital an-gle instrument, and group B didn’t use digital angle instrument. Group C had lung mass of>30 mm, and the biopsy was performed without using the instrument. The size of the mass, frequency of punctures, distance of the puncture, and complication of pneumotho-rax after puncture were compared among the three groups. Results: The maximum diameter of pulmonary nodules in group A (18.4 ± 2.1) mm was significantly lower than that in groups B (28.3 ± 2.0) mm and C (43.2 ± 3.6) mm, and their P value were 0.0034 and 0.0028, respectively. Some patients in group A were at risk because of severe chronic obstructive pulmonary disease and proximity of lesions to large blood vessels. The puncture distance in group A was also significantly more than groups B (P<0.039). However, the probability of puncture success in group A was 100%, which was significantly higher than groups B and C. The postoperative complica-tions in group A were also significantly fewer than in other two groups. Conclusions: CT-guided percutaneous lung biopsy with a digital angle instrument is a safe, simple, and accurate diagnostic method, especially in patients with pulmonary nodular lesions.

Objective To understand the management status quo of migrant workers with chronic hepatitis B (CHB) to ex‐plore the management countermeasures and improve the survival quality for tamping the foundation of the healthy project .Methods Totally 300 migrant workers with CHB were performed the living quality evaluation and investigation on the service needs ,com‐pliance ,economic condition ,categories and proportion of reimbursement by adopting the supplementary revision of SF‐36 living quality scale and general information questionnaire ;the influencing factors of their living quality were performed the univariate anal‐ysis and multivariate stepwise regression analysis .Results The statistical analysis found that whether convenient for outside visit‐ing hospital ,categories and proportion of reimbursement ,whether normalized antiviral therapy ,whether conducting examination and follow up at regular intervals and liver disease specific symptoms were the influencing factors of living quality in the migrant work‐ers with CHB(P<0 .05);the living quality in the patients with outside convenient visiting hospital ,high reimbursement proportion , normalized antiviral therapy and examination and follow up at regular intervals was significantly higher than that in the patients with inconvenient outside visiting hospital ,low reimbursement proportion ,non‐normalized anti‐viral therapy and examination and follow up without regular intervals(P<0 .05);the liver disease specific symptom score showed the positive correlation trend with the living quality score (B=7 .657 ,SD=2 .650 ,t=2 .889 ,P=0 .004) .Conclusion It is necessary to improve the patient′s medical needs ,reimbursement type and proportion ,increase the compliance of patient′s normalized examination and follow‐up at regular in‐tervals and standard antiviral treatment ,thus to realize the standardized examination and treatment in CHB patients ,prevent or de‐lay the disease progression ,avoid liver cirrhosis and decompensated hepatopathy ,reduce the occurrence of HCC ,improve the quality of life and prolong the survival period .

OBJECTIVETo explore the effects of different concentrations of putrescine on the proliferation, migration and apoptosis of human skin fibroblasts (HSF).

METHODSHSF cultured in the presence of 0.5, 1.0, 5.0, 10, 50, 100, 500, and 1000 µg/ putrescine for 24 h were examined for the changes in the cell proliferation, migration, and apoptosis using MTS assay, Transwell migration assay, and flow cytometry, respectively.

RESULTSCompared with the control cells, HSF cultured with 0.5, 1.0, 5.0, and 10 µg/ putrescine showed significantly increased cell proliferation (P<0.01), and the effect was the most obvious with 1 µg/ putrescine, whereas 500 and 1000 µg/ putrescine significantly reduced the cell proliferation (P<0.01); 50 and 100 µg/ did not obviously affect the cell proliferation (P>0.05). Putrescine at 1 µg/ most significantly enhanced the cell migration (P<0.01), while at higher doses (50, 100, 500, and 1000 µg/) putrescine significantly suppressed the cell migration (P<0.05); 0.5, 5.0, and 10 µg/ putrescine produced no obvious effects on the cell migration (P>0.05). HSF treated with 0.5, 1.0, 5.0, and 10 µg/ putrescine obvious lowered the cell apoptosis rate compared with the control group (P<0.01), and the cell apoptosis rate was the lowest in cells treated with 1 µg/ putrescine; but at the concentrations of 100, 500, and 1000 µg/, putrescine significantly increased the cell apoptosis rate (P<0.01), while 50 µg/ml putrescine produced no obvious effect on cell apoptosis (P>0.05).

CONCLUSIONLow concentrations of putrescine can obviously enhance the proliferation ability and maintain normal migration ability of HSF in vitro, but at high concentrations, putrescine can obviously inhibit the cell migration and proliferation and induce cells apoptosis, suggesting the different roles of different concentrations of putrescine in wound healing.

Apoptosis ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Fibroblasts ; cytology ; drug effects ; Flow Cytometry ; Humans ; Putrescine ; administration & dosage ; pharmacology ; Skin ; cytology ; Wound Healing