Generalized anxiety disorder (GAD) belongs to the category of emotional diseases in TCM, and its occurrence is closely related to liver depression and qi stagnation, and liver depression and fire syndrome is one of the TCM syndromes of GAD. With the deepening of modern medical research on GAD, microglia have been found to play an important role in the development of liver depression and fire syndrome of GAD. Excessive activation of microglia and transformation to M1 type would cause inflammatory mediator secretion up-regulation and destruction of neurons, etc. When using liver-soothing and heat-clearing medicines such as Bupleuri Radix, Gardeniae Fructus, Dangzhi Xiaoyao San, Yuejiu Pills and other Chinese materia medica or compounds, activation of microglia would be suppressed, and the inflammatory mediators mediated by microglia would also be suppressed, and the neurons could be protected. Therefore, this article discussed the modern biological connotation of the liver depression and fire syndrome of GAD from the perspective of microglia, and summarized the effects of TCM modulation of microglia on the liver depression and fire syndrome of GAD, and concluded that microglia could mediate the development of liver depression and fire syndrome of GAD.

Cetuximab is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR) for the treatment of metastat-ic colorectal cancer (mCRC). However,most patients treated with cetuximab experience disease progression due to the development of sec-ondary drug resistance,presenting a significant challenge in managing cetuximab therapy. Existing studies have found that cetuximab resist-ance mechanisms are not only linked to the RAS/RAF/PIK3CA genetic mutations but also closely associated with the abnormal activation of PI3K/AKT/mTOR,Wnt/β-catenin,c-MET/HGF,and RAS-MAPK signaling pathways. Additionally,HER2 and MET amplification,microsatellite instability,changes in tumor metabolism,and alterations in the tumor microenvironment may also contribute to cetuximab resistance in pa-tients. This review focuses on the potential molecular mechanisms of cetuximab resistance in the treatment of mCRC,and provides new ideas for overcoming cetuximab resistance in clinic.

Objective:To analyze the epidemiological features of respiratory syncytial virus (RSV) infection in Beijing, and monitor the sequence variations in RSV glycoprotein (G) gene and clinical features of infected children.Methods:Respiratory tract specimens were collected from children with acute respiratory infection in the Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 1, 2023 to December 31, 2023. RSV-positive specimens screened by multiple nucleic acid testing were subjected to PCR to amplify the full-length RSV G gene. A phylogenetic tree was constructed after gene sequencing to analyze RSV subtypes and trace G gene variants. Clinical data were retrieved from the medical record system to analyze the clinical features of children with RSV infection in Beijing.Results:A total of 5 489 respiratory specimens were collected from 3 046 male patients and 2 443 female patients. The average age of the patients was 4.36 years. A total of 589 RSV-positive specimens (10.7%, 589/5 489) were detected with 349 from male patients and 240 from female patients. The average age of children with RSV infection was (2.51±2.78) years and the median age was 0.48 years. RSV had been circulating among children in Beijing since March 2023 with two epidemic peaks in May (24.6%, 122/496) and December (18.2%, 126/693). The predominant subtype of RSV in the first half of 2023 was subtype A, but it was replaced by subtype B from November 2023. Phylogenetic analysis revealed a novel G gene of RSV subtype B (RSV-B-BA9-954bp) with a length of 954 bp, which belonged to a new cluster in the phylogenetic tree. The percentage of patients admitted to the Intensive Care Unit (ICU) was higher in children with new variant of RSV subtype B infection than in those with common RSV subtype B infection [44.1% (15/34) vs 25.2% (31/123), χ 2=4.600, P=0.032], while the counts of white blood cells and the levels of C-reactive protein were lower in the children with new variant infection ( P<0.05). Conclusions:RSV has been prevalent among children in Beijing since March 2023 with two epidemic peaks. The predominant A subtype is gradually replaced by to B subtype. A new variant of RSV B G gene (RSV-B-BA9-954bp) is detected among the children.

Objective:To analyze the differentially expressed genes of human respiratory syncytial virus (RSV) subtype A genotype ON1, a predominant genotype in Beijing, after infecting A549 cells using transcriptomic sequencing, and provide potential targets for RSV prevention and treatment.Methods:A local strain (61397-ON1) identified by whole-genome sequencing as ON1 genotype of RSV subtype A was selected to infect A549 cells. Total mRNA was extracted, and the differentially expressed genes in infected and uninfected A549 cells were screened by transcriptomic sequencing. GO analysis and KEGG pathway analysis were performed. Besides, six genes with differential expression ratio greater than two times were randomly selected for qRT-PCR verification.Results:There were 1 632 differentially expressed genes between infected and uninfected A549 cells, of which 807 genes were up-regulated and 825 genes were down-regulated. The differentially expressed genes were mainly involved in immune response-related biological processes such as cytokine response and positive regulation of MAPK cascades, and were enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, p53 signaling pathway, TNF signaling pathway, IL-17 signaling pathway and NF-κB signaling pathway. The results of qRT-PCR for six differentially expressed genes were consistent with the trend of transcriptome data.Conclusions:The differentially expressed genes of RSV A subtype ON1 genotype after infecting A549 cells are mainly involved in cytokine response and immune-related signaling pathways. This study provides basic data for further study of the molecular mechanism of RSV infection and the development of prevention and treatment strategies.

Cetuximab is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR) for the treatment of metastat-ic colorectal cancer (mCRC). However,most patients treated with cetuximab experience disease progression due to the development of sec-ondary drug resistance,presenting a significant challenge in managing cetuximab therapy. Existing studies have found that cetuximab resist-ance mechanisms are not only linked to the RAS/RAF/PIK3CA genetic mutations but also closely associated with the abnormal activation of PI3K/AKT/mTOR,Wnt/β-catenin,c-MET/HGF,and RAS-MAPK signaling pathways. Additionally,HER2 and MET amplification,microsatellite instability,changes in tumor metabolism,and alterations in the tumor microenvironment may also contribute to cetuximab resistance in pa-tients. This review focuses on the potential molecular mechanisms of cetuximab resistance in the treatment of mCRC,and provides new ideas for overcoming cetuximab resistance in clinic.

Objective:To investigate the application value of mixed reality technology in surgical conversation of laparoscopy radical resection of gastric cancer.Methods:The prospective randomized controlled study was conducted. There were 80 family members of patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June 2021 to December 2022 being selected as subjects. All patients underwent laparoscopic radical resection of gastric cancer. Based on random number table, all subjects were allocated into the control group and the experiment group. Subjects in the control group performed routine surgical conversation and subjects in the experiment group performed surgical conversation based on mixed reality technology. Observation indicators: (1) baseline data of the subjects; (2) anxiety assessment of the subjects. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for inter-group comparison. Repeated measurement data were analyzed using the repeated ANOVA. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. Results:(1) Baseline data of the subjects. A total of 80 subjects were selected for eligibility, including 40 subjects in the control group and 40 subjects in the experi-ment group. There were 44 males and 36 females, aged (40±9)years. The gender (male, female), age, education background (primary school education, middle school education, high school education, junior college education, undergraduate education, postgraduate education) were 23, 17, (39±9)years, 1, 3, 9, 16, 9, 2 in subjects of the control group, versus 25, 15, (42±10)years, 0, 8, 6, 11, 14, 1 in subjects of the experiment group, showing no significant difference in the above indicators between the two groups ( χ2=0.20, t=?1.64, Z=?0.10, P>0.05). (2) Anxiety assessment of the subjects. The scores of self-rating Anxiety Scale (SAS) and Hospital Anxiety Scale (HADS) before surgical conversation, after surgical conversation, after surgery were 41±10 and 26±5, 49±11 and 32±3, 40±13 and 15±8 in subjects of the control group, versus 44±9 and 23±3, 66±16 and 28±6, 34±14 and 8±3 in subjects of the experiment group, showing significant differences in the above indicators between the two groups ( FSAS组间=8.83, FSAS时间=40.41, FSAS交互=12.21, FHADS组间=32.42, FHADS时间=321.28, FHADS交互=6.15, P<0.05). Conclusion:Compared with traditional surgical conversation, mixed reality technology based surgical conversation can relieve the postoperative conxiety of subjects.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To investigate the application value of Overlap guiding tube (OGT) in Overlap esophagojejunostomy of laparoscopic total gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June to July in 2021 were collected. There were 3 males and 2 females, aged from 48 to 61 years, with a median age of 54 years. Patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone interview to detect postoperative anastomotic stenosis and esophageal reflux up to September 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations: 5 patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy and D 2 lymph node dissection success-fully, achieving R 0 resection. There was no combined organ resection, intraoperative conversion to laparotomy or combined thoracotomy. There was no intraoperative conversion to other esophagoje-junostomy method either. The tumor diameter, length of surgical incision, the number of lymph nodes dissected, time of esophagojejunal anastomosis, time of digestive reconstruction, operation time, volume of intraoperative blood loss of 5 patients were 3.0(2.8)cm, 5.0(2.0)cm, 47.0(21.0), 21.0(5.0)minutes, 62.0(23.0)minutes, 295.0(75.0)minutes, and 50.0(60.0)mL, respectively. The anvil fork of linear stapler was successfully inserted into esophageal lumen by once operation in 4 cases of 5 patients and by twice operation in 1 case to complete the esophagojejunostomy. (2) Post-operative situations: the time to first out-of-bed activities, time to postoperative first anal flatus, time to postoperative initial liquid diet intake, time to postoperative initial semi-liquid diet intake, time to abdominal drainage tube removal, duration of postoperative hospital stay of 5 patients were 2.0(1.0)days, 3.0(2.0)days, 4.0(3.0)days, 6.0(3.0)days, 7.0(4.0)days, and 9.0(6.0)days, respectively. Results of postoperative pathological examination of 5 patients showed gastric adenocar-cinoma in all the 5 patients, with the TNM staging as stage pT2-4aN0M0. The esophageal surgical margin was negative in all cases, and the length of proximal margin from esophagus was 5.0(4.0)cm. None of the 5 patients developed anastomotic leakage, anastomotic bleeding or anastomotic stenosis. Two cases with mild pneumonia (Clavien-Dindo grade Ⅱ) were cured by conservative treatment such as anti-infection and expectoration promotion. There was no unplanned secondary surgery or perioperative death occurred to the 5 patients. (3) Follow-up: 5 patients were followed up for 3 months. None of the 5 patients developed anastomotic stenosis or esophageal reflux during the follow-up. Conclusion:OGT-assisted Overlap esophagojejunostomy of laparoscopic total gas-trectomy is safe and feasible, with good short-term effects.

Objective:To analyze the risk of diabetes mellitus related to immune checkpoint inhibitors (ICI).Methods:The adverse event (AE) reports on fulminant type 1 diabetes mellitus (FT1DM), type 1 diabetes mellitus (T1DM), diabetic ketoacidosis (DKA), which were related to duvalizumab, pabolizumab, nivolumab, and atezolizumab in the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, were collected.The correlation between the 4 drugs and FT1DM, T1DM,and DKA were evaluated using proportional reporting odds ratio ( PRR) method.AE with reports ≥3, PRR value≥2, and χ2≥4 were judged to have statistical correlations with drugs. The greater the PRR value, the stronger the correlation between AE and drugs and the stronger the risk signals. Results:A total of 1 468 AE reports on diabetes mellitus were collected, 53, 386, 957, and 72 of which were related toduvalizumab, pabolizumab, nivolumab, and atezolizumab, respectively. For duvalizumab, pabolizumab, nivolumab, and atezolizumab, the PRR reflecting the correlation with FT1DM were 21.97 ( χ2=40.71), 71.50 ( χ2=3 531.21), 294.30 ( χ2=4 3915.75), and 33.58 ( χ2=279.70), respectively; the PRR reflecting correlation with T1DM were 12.12 ( χ2=162.08), 21.04 ( χ2=3391.17), 20.99 ( χ2=5816.11), and 9.71 ( χ2=224.81), respectively; the PRR reflecting correlation with DKA were 6.93 ( χ2=161.26), 4.78 ( χ2=426.52), 6.82 ( χ2=1797.15), and 3.04 ( χ2=41.84), respectively. The 4 drugs were statistically correlated with their corresponding AE. The order of risk signal intensity for corresponding AE was FT1DM > T1DM > DKA. The order of risk signal intensity for FT1DM were nivolumab > pabolizumab > duvalizumab > atezolizumab, for T1DM were pabolizumab ≈ nivolumab > duvalizumab > atezolizumab, for DKA were duvalizumab ≈ nivolumab > pabolizumab > atezolizumab. Conclusions:Duvalizumab, pabolizumab, nivolumab, and atezolizumab all can cause diabetes mellitus. The risk signal intensity was the strongest for FT1DM, followed by T1DM and DKA in order.

Objective:To understand the main adverse event (AE) related to denosumab and the risks and provide reference for the safe use of the drug in clinic.Methods:The AE reports on denosumab included in the US FDA Adverse Event Reporting System from the second quarter of 2010 to the first quarter of 2021 were collected, and the AE risk signals was explored using proportional reporting odds ratio ( PRR) method. AEs with ≥3 reports, PRR value ≥2, and χ2≥4 were defined as positive risk signals. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities 24.0. The PTs of top 50 adverse event reports and signal intensity were selected and analyzed. Results:A total of 132 764 AE reports with denosumab as the primary suspected drug were collected, involving 5 571 PTs, and 641 positive risk signals were selected. After the second screening, the top 50 PTs in the number of AE reports and the top 50 PTs with great PRR values were obtained, and 93 PTs were included in the analysis after sifting out the repeated, involving 114 617 AE reports. The top 5 PTs in the number of AE reports were off-label use (28.7%, 32 863/114 617), death (14.2%, 16 230/114 617), osteonecrosis of the jaw (6.0%, 6 861/114 617), arthralgia (4.7%, 5 420/114 617), and limb pain (4.1%, 4 727/114 617). The top 5 PTs with the high signal intensity were giant-cell tumour of bone ( PRR=402.7), malignant giant-cell tumour of bone ( PRR=325.2), C-telopeptide increase ( PRR=169.4), exostosis of jaw ( PRR=163.2), and ionised calcium abnormal ( PRR=158.1). The top 5 SOC involving AE reports were injury, poisoning and procedural complications (35.9%, 41 757/114 617), musculoskeletal and connective tissue disorders (32.7%, 37 455/114 617), general disorders and administration site conditions (18.2%, 20 814/114 617), surgical and medical procedures (4.1%, 4 744/114 617), and investigations (2.9%, 3 290/114 617). Forty-four PTs were not included in the drug instructions, of which 23 were related to the oral cavity. Conclusions:Denosumab AE with the most reports were off-label use and osteonecrosis of the jaw. The risk signals of osteonecrosis of the jaw and recurrence or deterioration of giant-cell tumor of bone was strong. Most of the AE risk signals that were not included in the instructions are oral problems.