Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To investigate the effects of arthroscopic modified suture-bridge surgery on shoulder stability,pain and imaging anatomical parameters of elderly patients with full-thickness rotator cuff injury.Methods A total of 104 elderly patients with full-thickness rotator cuff injury admitted to Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to June 2023 were selected and divided into the suture-bridge group and the modified group according to random number table method,with 52 cases in each group.Patients in the suture-bridge group underwent arthroscopic suture-bridge surgery,and patients in the modified group underwent arthroscopic modified suture-bridge surgery.Perioperative indexes,the range of motion of shoulder joint,American Shoulder and Elbow Surgeons(ASES)score,visual analogue scale(VAS)score,Constant shoulder function score,University of California Los Angeles(UCLA)shoulder score,recovery of shoulder joint,Sugaya classification of imaging before and after surgery,and the rate of complications were compared between the two groups.Results There was no significant difference in the length of incision,operation time,joint perfusion volume,intraoperative blood loss,or hospitalization time of patients between the two groups(P>0.05).The external rotation,forward flexion,and abduction ranges of motion 6 months after surgery of patients in the modified group were greater than those in the suture-bridge group(P<0.05);The ASES,Constant,and UCLA scores 6 months after surgery of patients in the modified group were higher than those in the suture-bridge group,while the VAS score was lower than that in the suture-bridge group,with statistically significant differences(P<0.05);The proportions of patients who experienced complete painlessness in shoulder joint,had the same range of motion as the healthy side,and recovered to work ability before surgery 6 months after surgery in the modified group were higher than those in the suture-bridge group,and the Sugaya classification of imaging in the modified group was better than that in the suture-bridge group,with statistically significant differences(P<0.05);There was no significant difference in the incidence of shoulder joint swelling,limb numbness,bleeding,or retear of patients between the two groups(P>0.05).Conclusion Arthroscopic modified suture-bridge surgery for elderly patients with full-thickness rotator cuff injury can relieve postoperative pain,improve shoulder joint function,expand range of motion of shoulder joint,and improve imaging anatomical parameters without increasing the rate of complications.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective To investigate the application value of systemic inflammatory response index(SIRI)in patients with acute-on-chronic liver failure(ACLF)and co-infection.Methods A retrospective analysis was performed for the clinical data of 579 ACLF patients with co-infection who were diagnosed and treated in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to March 2016,including demographic features,laboratory markers,and complications,and SIRI,Model for End-Stage Liver Disease(MELD)score,MELD combined with serum sodium concentration(MELD-Na)score,and Child-Pugh score were calculated.According to the results of follow-up on day 90,the patients were divided into survival group with 210 patients and death group with 369 patients.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test were used for comparison of categorical data between two groups.The binary logistic regression analysis was used to investigate the independent risk factors for 90-day death.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to assess the performance of SIRI,MELD-Na score,and Child-Pugh score in predicting the prognosis of ACLF patients with co-infection.The Kaplan-Meier survival analysis was performed based on the optimal cut-off value of SIRI.Results Among the 597 ACLF patients with co-infection,384(66.32%)had HBV-related ACLF and 114(19.69%)had alcohol-related ACLF;as for the main infection sites,316(54.58%)had abdominal infection and 133(22.97%)had pulmonary infection;the 90-day mortality rate was 63.73%.The multivariate logistic regression analysis showed that SIRI(odds ratio[OR]=1.177,95%confidence interval[CI]:1.117-1.239,P<0.05),blood ammonia(OR=1.009,95%CI:1.001-1.018,P<0.05),MELD-Na score(OR=1.047,95%CI:1.016-1.080,P<0.05),Child-Pugh score(OR=1.351,95%CI:1.054-1.730,P<0.05),age(OR=1.045,95%CI:1.021-1.070,P<0.05),comorbidity with hepatic encephalopathy(OR=2.269,95%CI:1.305-3.946,P<0.05),and comorbidity with acute kidney injury(OR=1.730,95%CI:0.990-3.023,P<0.05)were independent risk factors for 90-day death in ACLF patients with co-infection.The Pearson correlation analysis showed that SIRI was positively correlated with MELD-Na score(r=0.282,P<0.001)and Child-Pugh score(r=0.168,P<0.001).SIRI,MELD-Na score,and Child-Pugh score had an AUC of 0.855,0.734,and 0.690,respectively,in predicting 90-day death,and SIRI had a higher predictive efficiency than MELD-Na score and Child-Pugh score(Z=4.922 and 6.289,both P<0.001),with a sensitivity of 76.7%and a specificity of 82.9%.In addition,SIRI combined with MELD-Na score or Child-Pugh score improved the predictive efficiency of MELD-Na score(0.854 vs 0.734,Z=6.899,P<0.001)and Child-Pugh score(0.858 vs 0.690,Z=8.725,P<0.001).The patients with high SIRI(≥4.08)had a 90-day survival rate of 11.29%(36/319),which was significantly lower than that in the patients with low SIRI(<4.08)(χ2=225.24,P<0.001).Conclusion SIRI is an independent risk factor for death in ACLF patients with co-infection and has a good clinical value in predicting prognosis,with the advantages of convenience and low costs.

Objective To investigate the application value of systemic inflammatory response index(SIRI)in patients with acute-on-chronic liver failure(ACLF)and co-infection.Methods A retrospective analysis was performed for the clinical data of 579 ACLF patients with co-infection who were diagnosed and treated in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to March 2016,including demographic features,laboratory markers,and complications,and SIRI,Model for End-Stage Liver Disease(MELD)score,MELD combined with serum sodium concentration(MELD-Na)score,and Child-Pugh score were calculated.According to the results of follow-up on day 90,the patients were divided into survival group with 210 patients and death group with 369 patients.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test were used for comparison of categorical data between two groups.The binary logistic regression analysis was used to investigate the independent risk factors for 90-day death.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to assess the performance of SIRI,MELD-Na score,and Child-Pugh score in predicting the prognosis of ACLF patients with co-infection.The Kaplan-Meier survival analysis was performed based on the optimal cut-off value of SIRI.Results Among the 597 ACLF patients with co-infection,384(66.32%)had HBV-related ACLF and 114(19.69%)had alcohol-related ACLF;as for the main infection sites,316(54.58%)had abdominal infection and 133(22.97%)had pulmonary infection;the 90-day mortality rate was 63.73%.The multivariate logistic regression analysis showed that SIRI(odds ratio[OR]=1.177,95%confidence interval[CI]:1.117-1.239,P<0.05),blood ammonia(OR=1.009,95%CI:1.001-1.018,P<0.05),MELD-Na score(OR=1.047,95%CI:1.016-1.080,P<0.05),Child-Pugh score(OR=1.351,95%CI:1.054-1.730,P<0.05),age(OR=1.045,95%CI:1.021-1.070,P<0.05),comorbidity with hepatic encephalopathy(OR=2.269,95%CI:1.305-3.946,P<0.05),and comorbidity with acute kidney injury(OR=1.730,95%CI:0.990-3.023,P<0.05)were independent risk factors for 90-day death in ACLF patients with co-infection.The Pearson correlation analysis showed that SIRI was positively correlated with MELD-Na score(r=0.282,P<0.001)and Child-Pugh score(r=0.168,P<0.001).SIRI,MELD-Na score,and Child-Pugh score had an AUC of 0.855,0.734,and 0.690,respectively,in predicting 90-day death,and SIRI had a higher predictive efficiency than MELD-Na score and Child-Pugh score(Z=4.922 and 6.289,both P<0.001),with a sensitivity of 76.7%and a specificity of 82.9%.In addition,SIRI combined with MELD-Na score or Child-Pugh score improved the predictive efficiency of MELD-Na score(0.854 vs 0.734,Z=6.899,P<0.001)and Child-Pugh score(0.858 vs 0.690,Z=8.725,P<0.001).The patients with high SIRI(≥4.08)had a 90-day survival rate of 11.29%(36/319),which was significantly lower than that in the patients with low SIRI(<4.08)(χ2=225.24,P<0.001).Conclusion SIRI is an independent risk factor for death in ACLF patients with co-infection and has a good clinical value in predicting prognosis,with the advantages of convenience and low costs.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To investigate the effects of arthroscopic modified suture-bridge surgery on shoulder stability,pain and imaging anatomical parameters of elderly patients with full-thickness rotator cuff injury.Methods A total of 104 elderly patients with full-thickness rotator cuff injury admitted to Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to June 2023 were selected and divided into the suture-bridge group and the modified group according to random number table method,with 52 cases in each group.Patients in the suture-bridge group underwent arthroscopic suture-bridge surgery,and patients in the modified group underwent arthroscopic modified suture-bridge surgery.Perioperative indexes,the range of motion of shoulder joint,American Shoulder and Elbow Surgeons(ASES)score,visual analogue scale(VAS)score,Constant shoulder function score,University of California Los Angeles(UCLA)shoulder score,recovery of shoulder joint,Sugaya classification of imaging before and after surgery,and the rate of complications were compared between the two groups.Results There was no significant difference in the length of incision,operation time,joint perfusion volume,intraoperative blood loss,or hospitalization time of patients between the two groups(P>0.05).The external rotation,forward flexion,and abduction ranges of motion 6 months after surgery of patients in the modified group were greater than those in the suture-bridge group(P<0.05);The ASES,Constant,and UCLA scores 6 months after surgery of patients in the modified group were higher than those in the suture-bridge group,while the VAS score was lower than that in the suture-bridge group,with statistically significant differences(P<0.05);The proportions of patients who experienced complete painlessness in shoulder joint,had the same range of motion as the healthy side,and recovered to work ability before surgery 6 months after surgery in the modified group were higher than those in the suture-bridge group,and the Sugaya classification of imaging in the modified group was better than that in the suture-bridge group,with statistically significant differences(P<0.05);There was no significant difference in the incidence of shoulder joint swelling,limb numbness,bleeding,or retear of patients between the two groups(P>0.05).Conclusion Arthroscopic modified suture-bridge surgery for elderly patients with full-thickness rotator cuff injury can relieve postoperative pain,improve shoulder joint function,expand range of motion of shoulder joint,and improve imaging anatomical parameters without increasing the rate of complications.

Objective:To introduce the clinical application of "page-turning" superior pancreatic lymph node dissection in laparoscopic D2 radical gastrectomy for gastric cancer.Methods:Patients who were confirmed to have adenocarcinoma by preoperative gastroscopy and pathological biopsy, with tumor staging evaluated by imaging as cT1~4aN0~3M0, without neoadjuvant therapy, and without absolute surgical contraindications, underwent laparoscopic radical gastrectomy for gastric cancer with "page-turning" superior pancreatic lymph node dissection. The "page-turning" superior pancreatic lymph node dissection was performed in four steps: (1) Expose the posterior gastric mesentery and dissect No.11p lymph nodes; (2) Expose the left gastric mesentery and dissect No.7, No.8a and No.9 lymph nodes; (3) Expose the right gastric mesentery and dissect No.5 lymph nodes; (4) Expose the left edge of the portal vein and dissect No.12a lymph nodes.Results:From April 2018 to October 2024, 112 patients with gastric cancer underwent laparoscopic D2 radical gastrectomy with "page-turning" superior pancreatic lymph node dissection, including 21 cases in the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 78 cases in the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, and 13 cases in the Department of Gastrointestinal Surgery, Jilin Provincial People's Hospital. The TNM staging of all patients was as follows: 31 cases in stage Ⅰ, 24 cases in stage Ⅱ, and 57 cases in stage Ⅲ; 62 cases of differentiated adenocarcinoma and 50 cases of undifferentiated adenocarcinoma; the median length of tumors was 3.8 cm. All patients successfully completed the operation without conversion to open surgery, no intraoperative massive hemorrhage or postoperative death. The median total number of lymph nodes dissected in all patients was 32, and the median number of positive lymph nodes was 4.5. The overall postoperative complication rate was 5.4% (6/112), all of which were Clavien-Dindo grade Ⅱ, including pulmonary infection, pleural effusion, and incisional infection, all cured by symptomatic treatment. The median follow-up was 41.8 (2-78) months, with 7 cases lost to follow-up. During the follow-up period, 27 cases (25.7%) had tumor recurrence and 16 cases (15.2%) died.Conclusions:The "page-turning" superior pancreatic lymph node dissection technique is safe and feasible in laparoscopic radical gastrectomy for gastric cancer.

Objective:To investigate the dynamic characteristics of human papillomavirus (HPV) genomic integration during cervical lesion progression and the clinical value of HPV integration detection in stratify HPV-positive women, and to explore its molecular mechanisms in cervical carcinogenesis.Methods:A prospective cohort study was designed to enroll high-risk HPV (HR-HPV) positive women who underwent cervical cancer screening in Drum Tower Hospital Affiliated to Nanjing University Medical School and Nanjing Maternity and Child Health Care Hospital from July 2022 to July 2024. Cervical exfoliated cells samples were collected, and HPV whole genome targeted capture and high-throughput sequencing technology were used. The HPV integration patterns, host gene functional region distribution and pathway enrichment characteristics of 157 samples with different cervical lesions grades were analyzed, including 31 cases of normal cervix, 40 cases of cervical intraepithelial neoplasia (CIN) Ⅰ, 32 cases of CIN Ⅱ, 42 cases of CIN Ⅲ, and 12 cases of cervical cancer.Results:HR-HPV integration was detected in 80.2% (126/157) of the 157 HR-HPV positive samples. The incidence of HR-HPV integration in cervical cancer patients was 12/12, which was higher than that in normal women (77%, 24/31). The incidence of HPV16 integration was significantly higher in high-grade lesions, and the incidence of HPV16 integration was 43% (18/42) in CIN Ⅲ patients and 8/12 in cervical cancer patients ( P<0.001). A total of 14 438 integration events were detected in 126 samples with HPV integration. The integration sites were mainly distributed in the host intergenic region (51.0%, 7 359/14 438) and intronic region (38.1%, 5 494/14 438), and the integration frequency of viral L1 gene was the highest (28.4%, 4 498/16 781). Functional enrichment analysis showed that HPV integration-related host genes were significantly enriched in transport of small molecules,cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway, and purine ribonucleotide biosynthetic process, which synergistically drove carcinogenesis through multiple mechanisms. Conclusions:HPV integration events are significantly associated with the progression of cervical lesions. HPV integrated detection based on cervical exfoliated cells is expected to optimize the current screening strategy, reduce excessive intervention of HPV positive women and facilitate their accurate triage management.