Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

The use of CD20 monoclonal antibody in the treatment of children with refractory nephrotic syndrome (RNS) is a novel drug therapy in recent years. Some CD20 monoclonal antibodies have positive efficacy and few adverse reactions, which can reduce the use of hormone drugs and immunosuppressants to a certain extent. However, the treatment of nephrotic syndrome is off-label, and the application time in clinic is not long, especially for children′s RNS, and more high-quality clinical studies are still needed for long-term efficacy and safety. The application and safety research progress of CD20 monoclonal antibody (including rituximab, ofatumumab, obinutuzumab, etc.) in the treatment of children with RNS from the aspects of mechanism of action, clinical application, pharmacokinetic characteristics, adverse reactions monitoring, and prevention are reviewed in this article, so as to provide reference for rational and safe clinical use.

The use of CD20 monoclonal antibody in the treatment of children with refractory nephrotic syndrome (RNS) is a novel drug therapy in recent years. Some CD20 monoclonal antibodies have positive efficacy and few adverse reactions, which can reduce the use of hormone drugs and immunosuppressants to a certain extent. However, the treatment of nephrotic syndrome is off-label, and the application time in clinic is not long, especially for children′s RNS, and more high-quality clinical studies are still needed for long-term efficacy and safety. The application and safety research progress of CD20 monoclonal antibody (including rituximab, ofatumumab, obinutuzumab, etc.) in the treatment of children with RNS from the aspects of mechanism of action, clinical application, pharmacokinetic characteristics, adverse reactions monitoring, and prevention are reviewed in this article, so as to provide reference for rational and safe clinical use.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (T2DM) by enhancing insulin secretion and inhibiting glucagon secretion. GLP-1RA has good efficacy and safety, but it may have the risk of pancreatic injury. Its incidence is low, but it is more harmful. At present, the research conclusions of GLP-1RA-related pancreatic injury are not consistent. This article reviews the research progress of GLP-1RA-related pancreatic injury from the aspects of occurrence, possible mechanism, related clinical research, clinical manifestations, and management measures. The possible mechanisms include activation of stellate cells, induction of proliferation and metaplasia of pancreatic ductal epithelial cells, presence of immune rejection, and influence on the expression of pancreatic injury related genes. Pancreatitis is more common in GLP-1RA-related pancreatic injury, and its clinical manifestations are abdominal pain, nausea, vomiting, and the elevation of lipase and amylase. It is suggested that patients should be given necessary medication education before medication. Once relevant symptoms occur, acute pancreatitis should be considered and the medication should be stopped immediately. If pancreatitis is confirmed, GLP‐1RA treatment is not recommended.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (T2DM) by enhancing insulin secretion and inhibiting glucagon secretion. GLP-1RA has good efficacy and safety, but it may have the risk of pancreatic injury. Its incidence is low, but it is more harmful. At present, the research conclusions of GLP-1RA-related pancreatic injury are not consistent. This article reviews the research progress of GLP-1RA-related pancreatic injury from the aspects of occurrence, possible mechanism, related clinical research, clinical manifestations, and management measures. The possible mechanisms include activation of stellate cells, induction of proliferation and metaplasia of pancreatic ductal epithelial cells, presence of immune rejection, and influence on the expression of pancreatic injury related genes. Pancreatitis is more common in GLP-1RA-related pancreatic injury, and its clinical manifestations are abdominal pain, nausea, vomiting, and the elevation of lipase and amylase. It is suggested that patients should be given necessary medication education before medication. Once relevant symptoms occur, acute pancreatitis should be considered and the medication should be stopped immediately. If pancreatitis is confirmed, GLP‐1RA treatment is not recommended.

Objective:To analyze the relationship between perineural invasion and other clinicopathological factors and its effect on the prognosis of gastric cancer.Methods:The clinicopathological data of 665 patients with gastric cancer were retrospectively analyzed. According to the presence of perineural invasion, the patients were divided into perineural invasion positive group and perineural invasion negative group. The relationship between perineural invasion and other clinicopathological factors and its effect on the prognosis of gastric cancer were analyzed. After eliminating the potential confusion bias between the two groups by propensity score matching (PSM) , the differences of 5-year cumulative survival rate between the two groups of gastric cancer patients were compared.Results:The incidence of perineural invasion was 17.0% (113 cases) . The binary logistic regression analysis showed that the depth of tumor invasion and vascular tumor thrombus were independent factors influencing the occurrence of gastric cancer perineural invasion (all P<0.001) . Univariate analysis showed that age (>60 years) , tumor diameter (>4 cm) , borrmann classification, depth of invasion, lymph node metastasis, TNM stage, degree of differentiation, vascular tumor thrombus, perineural invasion, tumor nodule, tumor site, resection site, and surgical operation were the influencing factors for the prognosis of patients with gastric cancer ( P<0.05) , but multivariate analysis showed that age (>60 years) , tumor diameter (>4cm) , depth of invasion, lymph node metastasis, and positive vascular tumor thrombi were independent risk factors affecting the prognosis of gastric cancer patients ( P<0.05) .However, perineural invasion cannot be an independent factor influencing the poor prognosis of gastric cancer in a multivariate analysis. Survival analysis was performed after propensity matching scores, and it was found that there was no statistically significant difference in the five-year survival rate between the perineural invasion positive group and the perineural invasion negative group (34.6% vs 43.0%; χ2=1.713; P=0.191) ,and there was no significant difference in the survival curve analysis between the two. Conclusion:Most patients with gastric cancer of perineural invasion have poor prognosis, but perineural invasion cannot be an independent prognostic factor for the prognosis of gastric cancer.

Objective:To study the effect of enhanced recovery after surgery (ERAS) on intestinal function and gut microbiota changes in patients who underwent laparoscopic gastrectomy.Methods:From Aug. 2018 to Dec. 2019, 80 patients who underwent laparoscopic radical D2 gastrectomy for gastric cancer in the first Department of Gastrointestinal Surgery of Yantai Yuhuangding Hospital were selected. According to whether it adopts ERAS treatment or not, patients were divided into 2 groups (n=40) : ERAS group and traditional perioperative treatment group. The time of postoperative bowel sounds, the time of first exhaust and defecation, the proportion of antibiotic-related diarrhea and surgical site infection (SSI) were recorded. Stools were collected before operation, first time after operation, 1, 2 weeks and 1 month after operation. 16S rRNA sequencing method was used to identify the diversity and species of gut microbiota. The diversity index of intestinal flora in the perioperative period and changes in the proportion of probiotics (bifidobacterium and lactobacillus) were compared.Results:The appearance time of bowel sounds, the first exhaust and defecation time [ (16.25±6.41) h, (23.95±6.02) h, (34.95±9.34) h] in ERAS group were significantly earlier than those in the traditional treatment group [ (22.3±6.49) h, (28.45±7.12) h, (48.1±15.64) h], and the difference was statistically significant ( P<0.05) . The incidence of antibiotic-related diarrhea was higher in the traditional treatment group (3/40) than in ERAS group (1/40) , but the difference was not statistically significant ( P>0.05) . The ratio of postoperative SSI was slightly higher in ERAS group, but the difference was not statistically significant ( P>0.05) . In the perioperative period, the intestinal flora diversity index (Chao1 and Shannon index) and the proportion of probiotics (lactobacillus acidophilus and bifidobacterium) were not significantly different between the two groups before surgery ( P>0.05) ; while at the first time, one week, 2 weeks after the operation, and 1 month after the operation, ERAS group was higher than the traditional group ( P<0.05) ; and at each postoperative time point, the traditional group decreased significantly than the ERAS group. The first time decrease was the largest, ( P<0.05) ; With the passage of time after operation, the diversity of intestinal flora and the proportion of probiotics gradually recovered. By 1 month after operation, the two groups did not return to the preoperative gut microbiota diversity state or proportion. Conclusion:The concept of enhanced recovery after surgery (ERAS) promotes the recovery of intestinal function in patients with gastric cancer, does not reduce the proportion of antibiotic-associated diarrhea (AAD) or surgical site infections (SSI) , and maintains the diversity of gut microbiota balance and stability.

Objective:To investigate the value of brainstem auditory evoked potential (BAEPs) combined with cochlear electrogram (ECochG) monitoring in the protection of auditory function during microvascular decompression (MVD) for patients with facial spasm (HFS).Methods:Clinical data of 908 patients with HFS who received MVD treatment in our hospital from January 2018 to December 2020 were retrospectively analyzed. The patients were divided into BAEPs group ( n=309), ECochG group ( n=301) and BAEPs+ECochG group ( n=298) according to the different methods of auditory nerve function monitoring. Waveform extraction rate, mean extraction time, amplitude, latency, intraoperative warning effect of 3 monitoring methods, as well as hearing status immediately after surgery and during follow-up were compared in patents from the 3 groups. Results:(1) The overall waveform extraction rate in ECochG group and BAEPs+ECochG group was significantly higher than that in BAEPs group, and the average waveform extraction time in ECochG group and BAEPs+ECochG group was significantly shorter than that in BAEPs group ( P<0.05). The amplitude of compound action potential (CAP) wave in ECochG group was significantly higher than that of V wave in BAEPs group, and the latency of CAP wave was also significantly earlier than that of V wave ( P< 0.05). (2) A total of 48 patients of the 288 patients in the BAEPs group showed warning signs; a total of 73 of the 292 patients in the ECochG group showed warning signs; and a total of 65 of the 292 patients in the BAEPs+ECochG group showed warning signs. (3) There was significant difference in hearing grading (American Association of Otolaryngology Head and Neck Surgery [AAO-HNS] grading) among the 3 groups immediately after surgery ( H=18.041, P=0.000), and the average rank suggested that the hearing of patients in the BAEPs+ECochG group was superior to the other two groups. All patients were followed up for an average of 15 months (ranged 3-24 months); there was still a significant difference in AAO-HNS grading among the 3 groups ( H=29.625, P=0.000), and the hearing of patients in the BAEPs+ECochG group was still superior to the other two groups. Conclusion:The combined application of ECochG and BAEPs monitoring can reflect the changes of intraoperative hearing impairment comprehensively, accurately and timely, which is of great significance for the protection of auditory function in HFS patients during MVD.

Background:Previous study has found that harmine inhibited the proliferation of gastric cancer cells by down-regulating cyclooxygenase-2(COX-2)expression. However,its molecular mechanism is not fully clear. Aims:To investigate the effect of harmine on proliferation and apoptosis of gastric cancer cells,and explore the role of PTEN/Akt/MDM2 signaling pathway in this process. Methods:Human gastric adenocarcinoma cell line SGC-7901 and MKN-45 were treated with harmine at different concentrations(2,4,8,16,32 μg/mL)for 24,48,and 72 hours. The cell proliferation and apoptosis were detected by MTT assay and Hoechst staining,respectively. The expressions of PTEN,COX-2, phosphorylated Akt(p-Akt)and p-MDM2 were measured by Western blotting. Results:Harmine dose- and time-dependently inhibited proliferation and induced apoptosis of SGC-7901 and MKN-45 cells. Also,harmine dose-dependently increased PTEN expression,and inhibited p-Akt,p-MDM2 and COX-2 expressions in SGC-7901 and MKN-45 cells. Conclusions:Harmine may inhibit proliferation and induce apoptosis of gastric cancer cells via down-regulating COX-2 expression through PTEN/Akt/MDM2 signaling pathway.

Objective To investigate the current situation in Chinese rheumatologic physicians' clinical diagnosis and evaluation of Takayasu's arteritis (TA).Methods Nineteen rheumatology experts and three vascular surgery specialists in China were invited to make the nationwide investigation for the first time about the diagnosis and disease activity evaluation of TA in China,through the questionnaire survey on the internet.Weighted average was used to calculate the average scores of corresponding problems.Results Chinese experts mainly adopted 1990 American College of Rheumatology (ACR) classification criteria for clinical diagnosis of TA.In details,symptoms of age,limb claudication and amaurosis,signs including pulselessness or pulse weakening,vascular bruits,increasing bilateral pulse pressure and hypertension and acute phase reactants (APR) were critical to the clinical diagnosis of TA.Besides,noninvasive imaging examinations,such as computed tomography angiography (CTA),magnetic resonance angiography (MRA),vascular ultrasonography,and positron emission tomography (PET) were also of great importance.In the aspect of disease activity assessment,Chinese experts mainly used Kerr scoring tool.APR and noninvasive radiological examinations were considered with vital value.Some TA patients with carotid artery involvement were recommended using vascular ultrasonography,while others with pulmonary artery and thoracic/abdominal aorta trunk involvement were preferred CTA other than MRA.Conclusions APR and noninvasive imaging examinations were thought with great help to make clinical diagnosis and evaluation of TA for Chinese physicians.