OBJECTIVES: Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets. METHODS: Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2. RESULTS: The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2. CONCLUSIONS EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals ; Microglia/metabolism* ; Phagocytosis/physiology* ; Rats, Sprague-Dawley ; Neuralgia/physiopathology* ; Early Growth Response Protein 2/metabolism* ; Male ; Rats ; Spinal Cord/metabolism* ; Sciatic Nerve/injuries*

OBJECTIVES: To investigate the effect of amentoflavone (AF) for alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and inhibiting NLRP3/ASC/Caspase-1 axis-mediated pyroptosis. METHODS: Female BALB/c mice were randomly divided into control group, LPS group, and AF treatment groups at low, moderate and high doses (n=12). ALI models were established by tracheal LPS instillation, and in AF treatment groups, AF was administered by gavage 30 min before LPS instillation. Six hours after LPS instillation, the mice were euthanized for examining lung tissue histopathological changes, protein levels in BALF, and MPO levels in the lung tissue. In the in vitro experiment, RAW264.7 cells were pretreated with AF, AC (a pyroptosis inhibitor), or their combination for 2 h before stimulation with LPS and ATP. The changes in cell proliferation and viability were detected using CCK-8 assay, and IL-1β, IL-6, IL-18, and TNF-α levels were determined with ELISA. Immunohistochemistry, immunofluorescence assay, and immunoblotting were used to detect the protein levels of NLRP3, ASC, cleaved caspase-1, and GSDMD N in rat lung tissues and the treated cells. RESULTS: In mice with LPS exposure, AF treatment significantly improved lung pathologies and edema, reduced protein levels in BALF and pulmonary MPO level, inhibited the high expression of NLRP3/ASC/Aspase-1 axis, reduced the expression of GSDMD N, and lowered the release of IL-1β, IL-6, IL-18, and TNF‑α. In RAW264.7 cells with LPS and ATP stimulation, AF pretreatment effectively reduced cell death, inhibited activation of the NLRP3/ASC/Aspase-1 axis, and reduced GSDMD N expression and the inflammatory factors. The pyroptosis inhibitor showed a similar effect to AF, and their combination produced more pronounced effects in RAW264.7 cells. CONCLUSIONS Amentoflavone can alleviate ALI in mice possibly by inhibiting NLRP3/ASC/Caspase-1 axis-mediated cell pyroptosis.
Animals ; Pyroptosis/drug effects* ; Acute Lung Injury/pathology* ; Mice ; Mice, Inbred BALB C ; Female ; Lipopolysaccharides ; Biflavonoids/pharmacology* ; RAW 264.7 Cells ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1/metabolism* ; Lung

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.

Objective:To assess the efficacy of high-flow nasal cannula oxygen therapy for the respiratory support after tracheal extubation under general anesthesia in neonates.Methods:This was a prospective randomized controlled study. Ninety-four neonates undergoing general surgery under general anesthesia with endotracheal intubation and endotracheal tube removal following surgery from December 2022 to November 2023 in the Third Affiliated Hospital of Zhengzhou University were selected and divided into 2 groups ( n=47 each) by the random number table method: conventional oxygen therapy group (group C) and high-flow nasal cannula oxygen therapy group (group H). After the endotracheal tube was removed, group H underwent high-flow nasal cannula oxygen therapy: oxygen flow was 2 L·kg -1·min -1, the concentration and humidity of oxygen were both 100%, and the temperature was 37 ℃. Group C underwent conventional mask ventilation with the oxygen flow rate 5 L/min, oxygen concentration 100%, ventilation frequency about 25-35 times/min. The outcome measures were recorded from the time after extubation to the time before discharge from the operating theatre. The main outcome measures were the minimum SpO 2 and hypoxemia (SpO 2<90%), choking, laryngospasm and asphyxia. The secondary outcome measures were respiratory rate (immediate extubation, immediate discharge), minimum HR, and time to discharge from the operating theatre. Results:Compared with group C, the lowest SpO 2 was significantly increased, the incidence of hypoxemia and respiratory rate immediately after discharge from the operating room was decreased ( P<0.05), and no significant changes were found in the incidence of choking, laryngospasm and asphyxia, the lowest heart rate, respiratory rate immediately after tracheal extubation and time to discharge from the operating theatre in group H( P>0.05). Conclusions:High-flow nasal cannula oxygen therapy can improve oxygenation and significantly reduce the risk of hypoxemia when used for the respiratory support after tracheal extubation under general anesthesia in neonates.

OBJECTIVE: To investigate the effectiveness of finger reconstruction using nail flap anastomosing the nerve branch of the first toe nail bed. METHODS: Between January 2016 and December 2022, 18 patients (18 fingers) with thumb or finger nail bed defects were admitted. There were 12 males and 6 females, with an average age of 32 years (range, 19-42 years). Four cases were finger tip tissue damage caused by machine compression, and 4 cases were distal tissue necrosis after finger replantation. There were 9 cases of thumb injury, 3 cases of index finger injury, 5 cases of middle finger injury, and 1 case of ring finger injury. There were 11 cases of distal nail damage and 7 cases of distal nail root (including nail root) damage. The time from injury to admission was 1-5 hours, with an average of 2 hours. After debridement and anti-infection treatment for 5-7 days, the wounds in size of 1 cm×1 cm to 4 cm×3 cm were reconstructed by using nail flaps anastomosing the nerve branches of the first toe nail bed. The size of the nail flaps ranged from 1.5 cm×1.5 cm to 4.5 cm×3.5 cm. The donor sites were repaired with the flaps in 16 cases and skin graft in 2 cases. RESULTS: All nail flaps, flaps, and skin grafts survived after operation and the wounds healed by first intention. All patients were followed up 6-12 months (mean, 10 months). The nails of 18 cases were all grown, in which 16 cases had smooth nails with satisfactory appearances, 1 case had uneven nails, and 1 case had obvious scar hyperplasia around the suture opening. At 6 months after operation, the two-point discrimination of the skin flap was 4-8 mm (mean, 6 mm). Meanwhile, the skin grafts and flaps at the donor sites regained protective sensation, good abrasion resistance, and had no negative effect upon walking and wearing shoes. CONCLUSION The application of a nail flap that anastomoses the nerve branch of the first toe nail bed for finger reconstruction has minimal damage and can achieve good nail bed repair results.
Male ; Female ; Humans ; Adult ; Nails/injuries* ; Plastic Surgery Procedures ; Finger Injuries/surgery* ; Surgical Flaps/innervation* ; Skin Transplantation/methods* ; Toes/injuries* ; Soft Tissue Injuries/surgery* ; Treatment Outcome

Objective:To examine the effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA).Methods:The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up.Results:The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively ( W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively ( W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion:The use of thin struct bare stents for SIDSMA could obtained the expected safety and efficacy.

Objective:To examine the effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA).Methods:The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up.Results:The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively ( W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively ( W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion:The use of thin struct bare stents for SIDSMA could obtained the expected safety and efficacy.

Objective To investigate the changes in the expression of cold-inducible RNA-binding protein (CIRBP) in a radiation-induced lung injury model. Methods Thirty male C57BL/6 mice were randomly divided by body weight into control group (no intervention) and model group (single chest X-ray irradiation with a dose of 20 Gy to build a radiation-induced lung injury model). The mice were dissected five weeks after irradiation. Hematoxylin-eosin staining and Masson staining were used to observe the pathological changes of the lung tissue and the deposition of collagen fibers. Immunohistochemistry was used to measure the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the lung tissue. qRT-PCR was used to measure the expression of CIRBP mRNA in the lung tissue. The expression of CIRBP protein in the lung tissue was determined by the immunofluorescence assay and Western blot. Results Compared with the control group, the model group showed significant pulmonary vascular congestion, significant inflammatory cell infiltration, significant thickening of some alveolar septa, significantly increased IL-6 expression [(129.41 ± 5.58) vs (187.22 ± 34.77), t = 3.179, P < 0.05], significantly increased TNF-α expression [(137.52 ± 23.53) vs (187.02 ± 19.16), t = 5.069, P < 0.05], significantly increased CIRBP mRNA expression [(1 ± 0.08) vs (1.97 ± 0.39), t = 3.45, P < 0.05], and significantly increased CIRBP protein expression [(9.32 ± 1.26) vs (14.76 ± 1.61), t = 3.751, P < 0.05], by the immunofluorescence assay; [(1.13 ± 0.17) vs (1.49 ± 0.14), t = 2.819, P < 0.05], by Western blot). Conclusion The expression of CIRBP is significantly increased in the radiation-induced lung injury model, which may be an important pro-inflammatory factor in radiation-induced lung injury.

Objective:To learn about the levels of serum iodine and thyroid function indicators in adults with normal thyroid function in Liaoning Province, to establish the medical reference value range of serum iodine, and to explore the relationship between serum iodine and thyroid function indicators.Methods:From February 2017 to December 2018, one subdistrict and one rural township were selected as the survey sites in the coastal area (Gaizhou City of Yingkou) and inland area (Kangping County of Shenyang) of Liaoning Province, respectively. Permanent residents aged 18 and older who have lived there for 5 years or more were selected as the survey subjects. Blood samples were collected to test the levels of serum iodine and thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb)]. The percentile method was used to establish the 95% medical reference value range of serum iodine in adults with normal thyroid function, and Pearson correlation analysis was used to analyze the correlation between serum iodine and thyroid function indicators. Results:A total of 1 621 adults with normal thyroid function were examined, the median serum iodine was 62.0 μg/L, and the 95% medical reference value range was preliminarily determined as 37.0-103.0 μg/L. Among them, the medians serum iodine of males and females (826 and 795 cases) were 62.3 and 61.0 μg/L, respectively, and there was no significant difference between genders ( Z=- 1.26, P = 0.210). The medians serum iodine of adults in coastal and inland areas (827 and 794 cases) were 61.7 and 61.9 μg/L, respectively, and there was no significant difference between areas ( Z = - 0.16, P = 0.870). The medians serum iodine of adults aged 18 - 29, 30 - 39, 40 - 49, 50 - 59 and 60 - 80 (385, 392, 378, 253 and 213 cases) were 61.0, 61.0, 63.0, 65.0 and 62.0 μg/L, respectively, and the difference between ages was statistically significant ( H = 14.52, P = 0.006). Pearson correlation analysis showed that serum iodine was weakly correlated with the level of FT 4 ( r = 0.17, P < 0.001), but not with the levels of TSH, TPOAb and TgAb ( P > 0.05). Conclusions:This study has established the medical reference value range of serum iodine in adults with normal thyroid function in Liaoning Province. Serum iodine is not correlated with the levels of TSH, TPOAb and TgAb.