Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

To report 3 cases of acute generalized exanthematous pustulosis (AGEP) caused by hydroxychloroquine. All the 3 patients were females, aged 23, 30, and 28 years respectively. In cases 1 and 3, the rashes appeared 4 days and 12 days respectively after the treatment with hydroxychloroquine for systemic lupus erythematosus; case 2, who was 8 weeks pregnant, developed rashes 10 days after starting hydroxychloroquine treatment for antiphospholipid syndrome. All the 3 patients had high fever, and clinically presented with generalized round or oval-shaped edematous erythema on the face, neck, trunk and limbs, covered with a large number of pinhead-sized pustules, and with multiple erythema multiforme-like lesions on the trunk and both upper limbs, including targetoid lesions. Mutations in the IL36RN gene were identified in all the 3 patients: a homozygous mutation c.115+6T>C in the IL36RN gene was found in case 1, and her parents were heterozygous carriers; case 2 inherited the heterozygous mutation c.115+6T>C in the IL36RN gene from her mother; the heterozygous mutation c.115+6T>C found in case 3 was a de novo mutation. A diagnosis of AGEP was made in all the 3 cases. Cases 1 and 2 received subcutaneous injections of adalimumab in addition to the treatment of their underlying diseases, and skin lesions markedly regressed after 1 week of treatment; case 3 was treated with high-dose glucocorticoids, and lesions subsided after 4 weeks; no significant adverse reactions were observed in cases 1 and 2, however, femoral head necrosis was noted in case 3. During a follow-up period of 42 months, none of the patients experienced recurrence, and case 2 gave birth to a healthy baby boy after 8-month treatment.

Objective:To investigate the transcriptomic signature of refractory nasal polyps (NP) after endoscopic sinus surgery.Methods:Tissue samples were collected from 36 patients with NP who underwent endoscopic sinus surgery at the Seventh Affiliated Hospital of Sun Yat-sen University and the First Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021. Raw sequencing data of normal nasal mucosa samples were downloaded from publicly available GEO database (Accession Number: GSE136825). Differential expression genes (DEGs) and Gene Ontology (GO) enrichment analysis were conducted to analyze the differences between refractory NP and normal controls, as well as among refractory, controlled, and partially controlled NP. Hierarchical clustering method was employed to analyze the inflammatory endotypes of NP. Weighted Gene Co-expression Network Analysis (WGCNA) and STRING database were used in combination with Cytoscape software to identify the characteristic transcriptional expression profiles of refractory NP. R software (version 4.3.1) was used for statistical analysis.Results:Refractory NP patients had significantly higher asthma comorbidity rates than controlled/partially controlled groups ( P<0.05). The numbers and percentages of peripheral blood and tissue eosinophilic granulocytes were significantly higher in the refractory subgroup than in the other two subgroups ( P<0.05). Compared to normal mucosa, controlled and partially controlled NP groups, 27 genes were consistently upregulated in refractory NP. Hierarchical cluster analysis showed that the refractory NP exhibited a mixed endotype dominated by type 2 inflammation with co-existing type 1 features. Differential genes were enriched in extracellular matrix organization, leukocyte activation, cytokine receptor activation, cystatin-mediated protease inhibition, granule exocytosis, and olfactory nerve development regulation. Further WGCNA analysis and protein-protein interaction network identified 33 hub genes represented by ITGAM, NCF1, NCF2, CD1C, PTAFR, CLEC10A, SIRPA, TREM2, ALOX5AP, PTGDR2 (officially PTGDR), F13A1, DUOX2, NOS2, CTSG, and SALL1.Conclusion:This study reveals the distinctive transcriptional signature of refractory NP through transcriptomic methods, providing novel research avenues and therapeutic targets for the treatment of refractory NP after surgery.

To report 3 cases of acute generalized exanthematous pustulosis (AGEP) caused by hydroxychloroquine. All the 3 patients were females, aged 23, 30, and 28 years respectively. In cases 1 and 3, the rashes appeared 4 days and 12 days respectively after the treatment with hydroxychloroquine for systemic lupus erythematosus; case 2, who was 8 weeks pregnant, developed rashes 10 days after starting hydroxychloroquine treatment for antiphospholipid syndrome. All the 3 patients had high fever, and clinically presented with generalized round or oval-shaped edematous erythema on the face, neck, trunk and limbs, covered with a large number of pinhead-sized pustules, and with multiple erythema multiforme-like lesions on the trunk and both upper limbs, including targetoid lesions. Mutations in the IL36RN gene were identified in all the 3 patients: a homozygous mutation c.115+6T>C in the IL36RN gene was found in case 1, and her parents were heterozygous carriers; case 2 inherited the heterozygous mutation c.115+6T>C in the IL36RN gene from her mother; the heterozygous mutation c.115+6T>C found in case 3 was a de novo mutation. A diagnosis of AGEP was made in all the 3 cases. Cases 1 and 2 received subcutaneous injections of adalimumab in addition to the treatment of their underlying diseases, and skin lesions markedly regressed after 1 week of treatment; case 3 was treated with high-dose glucocorticoids, and lesions subsided after 4 weeks; no significant adverse reactions were observed in cases 1 and 2, however, femoral head necrosis was noted in case 3. During a follow-up period of 42 months, none of the patients experienced recurrence, and case 2 gave birth to a healthy baby boy after 8-month treatment.

Objective:To investigate the transcriptomic signature of refractory nasal polyps (NP) after endoscopic sinus surgery.Methods:Tissue samples were collected from 36 patients with NP who underwent endoscopic sinus surgery at the Seventh Affiliated Hospital of Sun Yat-sen University and the First Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021. Raw sequencing data of normal nasal mucosa samples were downloaded from publicly available GEO database (Accession Number: GSE136825). Differential expression genes (DEGs) and Gene Ontology (GO) enrichment analysis were conducted to analyze the differences between refractory NP and normal controls, as well as among refractory, controlled, and partially controlled NP. Hierarchical clustering method was employed to analyze the inflammatory endotypes of NP. Weighted Gene Co-expression Network Analysis (WGCNA) and STRING database were used in combination with Cytoscape software to identify the characteristic transcriptional expression profiles of refractory NP. R software (version 4.3.1) was used for statistical analysis.Results:Refractory NP patients had significantly higher asthma comorbidity rates than controlled/partially controlled groups ( P<0.05). The numbers and percentages of peripheral blood and tissue eosinophilic granulocytes were significantly higher in the refractory subgroup than in the other two subgroups ( P<0.05). Compared to normal mucosa, controlled and partially controlled NP groups, 27 genes were consistently upregulated in refractory NP. Hierarchical cluster analysis showed that the refractory NP exhibited a mixed endotype dominated by type 2 inflammation with co-existing type 1 features. Differential genes were enriched in extracellular matrix organization, leukocyte activation, cytokine receptor activation, cystatin-mediated protease inhibition, granule exocytosis, and olfactory nerve development regulation. Further WGCNA analysis and protein-protein interaction network identified 33 hub genes represented by ITGAM, NCF1, NCF2, CD1C, PTAFR, CLEC10A, SIRPA, TREM2, ALOX5AP, PTGDR2 (officially PTGDR), F13A1, DUOX2, NOS2, CTSG, and SALL1.Conclusion:This study reveals the distinctive transcriptional signature of refractory NP through transcriptomic methods, providing novel research avenues and therapeutic targets for the treatment of refractory NP after surgery.

Objective To observe the value of spectral CT multi-parameter imaging for preoperative predicting lymph node metastasis(LNM)of gastric cancer.Methods Totally 136 patients with gastric adenocarcinoma were retrospectively enrolled.The patients were further divided into LNM group(n=74)and non-LNM group(n=62)according to postoperative pathological findings of lymph nodes status.Clinical data,conventional CT findings and spectral CT parameters were compared between groups.Factors being significant different between groups were included in multivariate logistic regression analysis to screen independent predictors of gastric cancer LNM.Clinical+conventional CT model(model 1),spectrum CT model(model 2)and combined model(model 3)were constructed based on the above independent predictors,respectively.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for preoperative predicting LNM of gastric cancer.Results CT-N stage,CT-T stage,70,100 and 140 keV CT valuestumor at arterial phase(AP),arterial enhancement fraction(AEF)and normalized iodine concentration at venous phase(NICVP)were all independent predictors of gastric cancer LNM(all P＜0.05).AUC of model 3 was 0.846,higher than that of model 1 and model 2(AUC=0.767,0.774,Z=-0.368,-2.373,both P＜0.05)for preoperative predicting LNM of gastric cancer,while the latter two were not significantly different(Z=-0.152,P=0.879).Conclusion Spectral CT multi-parameter imaging could effectively predict LNM of gastric cancer preoperatively.

Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.

Objective:To explore the application effect of the teaching method combining process-oriented-guided inquiry learning (POGIL) theory and micro-class in orthopedic clinical internship.Methods:The 118 interns who completed internship from January 2022 to December 2022 were randomly divided into a control group (58) and an experimental group (60). The control group received traditional teaching, while the experimental group received a teaching method combining POGIL theory and micro-class. After the internship, the two groups were compared for assessment scores (basic theoretical knowledge and professional theoretical knowledge), learning status (classroom performance and self-learning ability), clinical practice ability (Leicester Assessment Scale), and teaching satisfaction. The t-test and chi-square test were performed using SPSS 21.0. Results:After the internship, the assessment scores, classroom performance, self-directed learning ability scores, clinical skills, case writing scores, and teaching satisfaction of the experimental group were all higher than those of the control group ( t/ χ2=5.01, 3.72, 2.20, 6.57, 3.56, 4.52, P<0.05). Conclusions:The teaching method combining POGIL theory and micro-class can enhance the master of theoretical knowledge by orthopedic interns, optimize classroom performance, cultivate self-learning ability, and improve clinical practice ability and teaching satisfaction.

Mild autonomous cortisol secretion (MACS) is a condition indicated by biochemical testing for autonomous cortisol secretion, yet it lacks the classical signs of Cushing's Syndrome, such as moon face, buffalo hump, plethoric appearance, and purple striae. It is predominantly observed in middle-aged women and is commonly associated with adrenal incidentalomas. Due to the lack of significant clinical signs, the diagnosis of MACS primarily relies on hormonal testing. Patients with MACS often present with comorbidities such as hypertension, diabetes, and osteoporosis. For those with comorbid conditions, surgical treatment is the principal therapeutic approach. This article summarizes recent national and international guidelines and research to elucidate the updates to the diagnostic criteria for MACS, with a particular focus on the interpretation of the 1 mg overnight dexamethasone suppression test results. It also details the treatment and follow-up strategies for MACS. Furthermore, the article highlights the urgent need for more extensive prospective studies to refine the existing diagnostic criteria and to develop surgical guidelines for a wider range of patients with MACS.

Background/Aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options. Results: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. Conclusions Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.