The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Chest low-dose computed tomography (LDCT) is a widely utilized modality for lung cancer screening and follow-up in high-risk populations, owing to its low radiation dose. However, the diagnostic accuracy of LDCT is significantly constrained by inherent limitations, including elevated image noise and reduced contrast resolution. The potential for deep learning technologies to address these challenges through data-driven LDCT image denoising approaches has been demonstrated. In this review, the advantages and limitations of deep learning models were introduced, including supervised, unsupervised, and self-supervised learning. The potential and challenges of these models in clinical applications were analyzed, thereby providing a reference for subsequent research and clinical practice.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

AIM:To observe the role of enoyl-coenzyme A hydratase/L-3-hydroxyacyl-coenzyme A dehydroge-nase(Ehhadh)in renal tubulointerstitial inflammation in high-fat diet(HFD)fed mice,and to explore its molecular mecha-nism.METHODS:Twenty-four C57BL/6N mice were randomly divided into 4 groups:standard diet(SD)group,HFD group,HFD with Ehhadh overexpression(HFD+Ehh)group and HFD with blank vector(HFD+Vec)group.Each group consisted of 6 mice.The HFD mice were fed with a diet containing 60%fat,20%protein,and 20%carbohydrates for 16 weeks.Briefly,at the end of 8 weeks,the mice in HFD+Ehh or HFD+Vec group were injected with adeno-associated virus 9(AAV9)-Ehhadh or AAV9-vector via the tail vein,and then continued another 8-week HFD feeding.At the end of the experiments,the renal function and morphological changes were observed.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 p10,interleukin-1β(IL-1β)and IL-18 in the kidney were detected by Western blot and immunohistochemistry.Immunofluorescence staining was used to detect the colocalization of Ehhadh and peroxisomal biogenesis factor 14(Pex14).ELISA was used to detect the content of IL-1β and IL-18 in the urine.Lipid droplet formation in renal tissues was detected by Nile red staining.Absolute quantitative lip-idomic analysis were used to detect the differential lipid species in renal cortices of the mice in SD,HFD and HFD+Ehh groups.RESULTS:Compared with SD group,the expression of Ehhadh protein was significantly decreased in the peroxi-some of renal tubular epithelium cells in HFD-fed mice(P<0.01).Overexpression of Ehhadh significantly improved renal function(P<0.01)and alleviated the morphological changes of renal tubular epithelial cells in HFD group.Moreover,it significantly inhibited the expression of inflammatory cytokines IL-1β and IL-18 and macrophage infiltration in renal tu-bule interstitium of HFD-fed mice(P<0.01).At the same time,Ehhadh overexpression inhibited HFD-induced NLRP3 inflammasome activation(P<0.01).It also attenuated lipid deposition in renal tubular epithelium cells(P<0.01)and promoted the β-oxidation of long-chain fatty acid such as cholesterol and phospholipids in peroxisomes.CONCLUSION:The Ehhadh inhibits tubulointerstitial inflammation by promoting long-chain fatty acid β-oxidation in peroxisomes and in-hibiting the activation of NLRP3 inflammasome in HFD-fed mice.

Objective To retrospectively assess the clinical efficacy of acupuncture at the Huiyin point combined with Qingdu wash solution in the treatment of high-risk HPV infection.Methods A total of 264 patients who were initially diagnosed with high-risk HPV infection at the University City Gynecology Department of Guang-dong Provincial Hospital of Traditional Chinese Medicine between January 2022 and June 2024 were enrolled in the study.These patients were divided into two groups based on predefined inclusion and exclusion criteria.The ob-servation group included 134 patients who received acupuncture at the Huiyin acupoint combined with Qingdu wash solution,while the control group consisted of 130 patients who did not receive any intervention.The treatment pe-riod lasted for three months,during which the short-term clinical efficacy and safety profile were evaluated.Results The HR-HPV clearance rates in the observation group at 3 months and 6 months were 61.9%and 65.7%,respectively,which were significantly higher than those in the control group(16.9%and 21.5%),and the differences between the two groups were statistically significant(P<0.001).Following a three-month treatment regimen,the rate of HR-HPV positive-to-negative conversion in the observation group was significantly higher than that in the control group,with a statistically significant intergroup difference(P<0.001).The improvement in tra-ditional Chinese medicine(TCM)-related symptoms was also significantly better in the observation group compared to the control group(P<0.05).During the follow-up period,no cases of recurrence were observed in the observa-tion group,whereas the recurrence rate in the control group was 1.5%.Furthermore,no adverse reactions were re-ported in the observation group throughout the treatment period.Conclusion Acupuncture at the Huiyin point,when combined with Qingdu wash solution,can enhance the therapeutic outcomes of high-risk HPV infection and demonstrates a favorable safety profile.

Objective To retrospectively assess the clinical efficacy of acupuncture at the Huiyin point combined with Qingdu wash solution in the treatment of high-risk HPV infection.Methods A total of 264 patients who were initially diagnosed with high-risk HPV infection at the University City Gynecology Department of Guang-dong Provincial Hospital of Traditional Chinese Medicine between January 2022 and June 2024 were enrolled in the study.These patients were divided into two groups based on predefined inclusion and exclusion criteria.The ob-servation group included 134 patients who received acupuncture at the Huiyin acupoint combined with Qingdu wash solution,while the control group consisted of 130 patients who did not receive any intervention.The treatment pe-riod lasted for three months,during which the short-term clinical efficacy and safety profile were evaluated.Results The HR-HPV clearance rates in the observation group at 3 months and 6 months were 61.9%and 65.7%,respectively,which were significantly higher than those in the control group(16.9%and 21.5%),and the differences between the two groups were statistically significant(P<0.001).Following a three-month treatment regimen,the rate of HR-HPV positive-to-negative conversion in the observation group was significantly higher than that in the control group,with a statistically significant intergroup difference(P<0.001).The improvement in tra-ditional Chinese medicine(TCM)-related symptoms was also significantly better in the observation group compared to the control group(P<0.05).During the follow-up period,no cases of recurrence were observed in the observa-tion group,whereas the recurrence rate in the control group was 1.5%.Furthermore,no adverse reactions were re-ported in the observation group throughout the treatment period.Conclusion Acupuncture at the Huiyin point,when combined with Qingdu wash solution,can enhance the therapeutic outcomes of high-risk HPV infection and demonstrates a favorable safety profile.

AIM:To observe the role of enoyl-coenzyme A hydratase/L-3-hydroxyacyl-coenzyme A dehydroge-nase(Ehhadh)in renal tubulointerstitial inflammation in high-fat diet(HFD)fed mice,and to explore its molecular mecha-nism.METHODS:Twenty-four C57BL/6N mice were randomly divided into 4 groups:standard diet(SD)group,HFD group,HFD with Ehhadh overexpression(HFD+Ehh)group and HFD with blank vector(HFD+Vec)group.Each group consisted of 6 mice.The HFD mice were fed with a diet containing 60%fat,20%protein,and 20%carbohydrates for 16 weeks.Briefly,at the end of 8 weeks,the mice in HFD+Ehh or HFD+Vec group were injected with adeno-associated virus 9(AAV9)-Ehhadh or AAV9-vector via the tail vein,and then continued another 8-week HFD feeding.At the end of the experiments,the renal function and morphological changes were observed.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 p10,interleukin-1β(IL-1β)and IL-18 in the kidney were detected by Western blot and immunohistochemistry.Immunofluorescence staining was used to detect the colocalization of Ehhadh and peroxisomal biogenesis factor 14(Pex14).ELISA was used to detect the content of IL-1β and IL-18 in the urine.Lipid droplet formation in renal tissues was detected by Nile red staining.Absolute quantitative lip-idomic analysis were used to detect the differential lipid species in renal cortices of the mice in SD,HFD and HFD+Ehh groups.RESULTS:Compared with SD group,the expression of Ehhadh protein was significantly decreased in the peroxi-some of renal tubular epithelium cells in HFD-fed mice(P<0.01).Overexpression of Ehhadh significantly improved renal function(P<0.01)and alleviated the morphological changes of renal tubular epithelial cells in HFD group.Moreover,it significantly inhibited the expression of inflammatory cytokines IL-1β and IL-18 and macrophage infiltration in renal tu-bule interstitium of HFD-fed mice(P<0.01).At the same time,Ehhadh overexpression inhibited HFD-induced NLRP3 inflammasome activation(P<0.01).It also attenuated lipid deposition in renal tubular epithelium cells(P<0.01)and promoted the β-oxidation of long-chain fatty acid such as cholesterol and phospholipids in peroxisomes.CONCLUSION:The Ehhadh inhibits tubulointerstitial inflammation by promoting long-chain fatty acid β-oxidation in peroxisomes and in-hibiting the activation of NLRP3 inflammasome in HFD-fed mice.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Digestive tract tumors are currently one of the most common types of cancer,including esophageal cancer,gastric cancer,hepatocellular carcinoma,pancreatic cancer,and colorectal cancer.Their prognoses are poor and the treatments require further improvement.Caveolin-1(CAV1)has a dual regulatory effect on digestive tract tumors as a tumor suppressor and cancer promoter.CAV 1 plays a major role in cell proliferation,invasion,metastasis,angiogenesis,and drug tolerance of digestive tract tumors.The regulation of CAV1 protein and its related signaling pathways may be a strategy for the treatment of digestive tract tumors.This review analyzes the relationship between CAV 1 and digestive tract tumors in terms of structure,function,expression regulation,regulation of epithelial-mesenchymal transition,and drug resistance in digestive tract tumors to provide new ideas for the diagnosis and treatment of digestive tract tumors.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.