Objective:To evaluate the feasibility of a novel flexible ultrasound imaging catheter for high-resolution real-time imaging of deep abdominal structures via percutaneous intervention.Methods:A self-developed flexible ultrasound catheter system（outer diameter：3.3 mm，integrated with a 10.5 MHz high-frequency linear array transducer and 4-degree-of-freedom active deflection）was used to image abdominal organs（liver，gallbladder，pancreas，etc.）in two healthy beagles via percutaneous puncture，with comparison to conventional surface convex array probes（3.6 MHz）. Image quality was assessed using a double-blind design，independently scored by five ultrasound physicians with over 10 years of experience on a 6-point scale. Mixed-effects ordinal logistic regression（adjusted for dog，organ，and evaluator variability）was employed for inter-group comparisons，with effect sizes quantified by Cliff's delta. Characteristic anatomical structure detection rates were analyzed using generalized linear mixed models（Firth correction for zero events）. Inter-rater reliability was assessed via intraclass correlation coefficient（ICC，two-way random model）and Kendall's coefficient of concordance.Results:The flexible catheter group demonstrated significantly superior image quality compared to the surface probe group . The most pronounced improvement was observed in adrenal imaging（5 points vs. 1 point， P<0.001，δ=0.92），while pancreatic imaging showed no significant difference（2 points vs. 2 points， P=0.812，δ=0.05）. Other organs exhibited significant quality enhancements（all P<0.05，δ=0.63～0.81）. The catheter significantly improved detection rates of characteristic structures：gastric wall stratification（90% vs. 10%， OR=36.0， P<0.001），adrenal corticomedullary differentiation（80% vs. 0， OR=∞， P<0.001），and gallbladder/small intestinal wall trilaminar structure（80% vs. 20%， OR=12.0， P=0.003）. The high-quality image rate（≥5 points）reached 77.8%，representing an 11.6-fold improvement over surface ultrasound（6.7%， P<0.001）. Inter-rater reliability was excellent（ICC=0.85，W=0.79）. Conclusions:Percutaneous flexible ultrasound catheter imaging significantly enhances resolution and anatomical detail visualization of deep abdominal structures. Combining minimally invasive access with operational flexibility，this technology shows promise for providing precise image guidance in minimally invasive procedures.

To study the immunoregulatory effects of lycorine on mice infected with Toxoplasma gondii(T.gondii),BALB/c mice were treated with 20 mg/kg lycorine solution after peritoneal in-fection with T.gondii RH strain.The serum and spleen of mice were collected at the 1st,3rd,5th and 7th day,respectively,and the spleen index of mice was calculated.The proportion of T lympho-cyte subtypes and NK cells were detected in mice by flow cytometry,and the changes of cytokine levels in mice were measured using ELISA kit,so as to evaluate the immunomodulatory effect of lycorine on mice infected with T.gondii.At the same time,the heart,liver,spleen,lungs,and kid-neys of mice were collected at the 7th day,and the pathological changes of the mouse organs were observed through pathological tissue sections,and the amount of the parasite in the liver,lung,kid-ney,and brain of the mice was detected by fluorescence quantitative PCR.The results showed that the survival time of the mice treated with lycorine was significantly extended,and the survival rate reached 80％.The spleen index of mice treated with lycorine was lower than that of the control group.Lycorine up-regulates the ratio of the CD4+T lymphocytes and NK cells in the spleen of mice infected with T.gondii,and helps to improve the ability of mice to resist T.gondii infection.Lycorine can up-regulate the levels of anti-inflammatory cytokine IL-4 and down-regulate the lev-els of pro-inflammatory factors IFN-γ,IL-1β,and IL-9 in serum of mice infected with T.gondii,which is conducive to reducing the damage of inflammatory response and enhancing the ability of anti-T.gondii infection.In addition,lycorine can alleviate the pathological damage of T.gondii to the liver,lungs,spleen,and kidneys of mice,and significantly reduce the amount of the parasite in the lung of mice.The results showed that lycorine could up-regulate the proportion of immune cells CD4+T lymphocytes and NK cells,inhibit the inflammatory response of mice infected with T.gondii,reduce the pathological damage of mice organs,and enhance the ability of mice to resist T.gondii infection,which is expected to become a novel anti-T.gondii drug.

Objective To investigate the efficacy of Yiqi Wenyang Sanjie Decoction in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution,and to observe its effect on serum inflammatory factors and immune function.Methods From January 2020 to June 2024,a total of 106 patients with pulmonary ground glass nodules and yang-deficiency constitution admitted to the Department of Respiratory Medicine and Preventive Treatment of Disease Center of Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine were selected.The patients were randomly divided into control group and Chinese medicine group by random number table method,with 53 cases in each group.The patients in the control group were only given follow-up without any intervention,and the patients in the Chinese medicine group were treated with Yiqi Wenyang Sanjie Decoction for 3 months.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,maximum diameter of pulmonary ground glass nodules,serum levels of inflammatory factors of interleukin-6(IL-6),interleukin-17A(IL-17A),and tumor necrosis factor-α(TNF-α),and levels of immune function indicators of peripheral blood CD3+,CD4+cell percentage and CD4+/CD8+ratio.After treatment,the efficacy and safety of the two groups were evaluated.Results(1)During the trial,5 cases fell off from the control group and 3 cases fell off from the Chinese medicine group.A total of 98 cases were eventually included,and 48 cases were in the control group and 50 cases were in the Chinese medicine group.(2)After 3 months of treatment,the total effective rate of the Chinese medicine group was 46.00%(23/50),and that of the control group was 10.42%(5/48).The intergroup comparison(tested by chi-square test)showed that the efficacy of the Chinese medicine group was significantly superior to that of the control group(P＜0.01).(3)After treatment,the TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group were lowered(P＜0.05),while the TCM syndrome score and the maximum diameter showed no obvious changes compared with those at enrollment(P＞0.05);the intergroup comparison showed that the reduction of TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the levels of serum inflammatory factors of IL-6,IL-17A and TNF-α in the Chinese medicine group were significantly lowered compared with those at enrollment(P＜0.05),while there was no significant change in serum IL-6,IL-17A and TNF-α levels of the control group(P＞0.05);the intergroup comparison showed that the decrease of serum IL-6,IL-17A and TNF-α levels in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the percentage of T lymphocyte subset CD4+and the ratio of CD4+/CD8+in the Chinese medicine group were significantly increased compared with those at enrollment(P＜0.05),while there was no significant change in the percentage of CD3+,CD4+cells and the ratio of CD4+/CD8+of the control group and in the percentage of CD3+cells of the Chinese medicine group(P＞0.05).The intergroup comparison showed that the increase of CD4+percentage and CD4+/CD8+ratio in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(6)There were no obvious adverse reactions occurring in the Chinese medicine group during the treatment,showing relatively high safety.Conclusion Yiqi Wenyang Sanjie Decoction exerts certain effect in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution.It can effectively promote the reduction of nodules,relieve clinical symptoms,decrease serum levels of inflammatory factors,improve immune function,and has good safety.

To study the immunoregulatory effects of lycorine on mice infected with Toxoplasma gondii(T.gondii),BALB/c mice were treated with 20 mg/kg lycorine solution after peritoneal in-fection with T.gondii RH strain.The serum and spleen of mice were collected at the 1st,3rd,5th and 7th day,respectively,and the spleen index of mice was calculated.The proportion of T lympho-cyte subtypes and NK cells were detected in mice by flow cytometry,and the changes of cytokine levels in mice were measured using ELISA kit,so as to evaluate the immunomodulatory effect of lycorine on mice infected with T.gondii.At the same time,the heart,liver,spleen,lungs,and kid-neys of mice were collected at the 7th day,and the pathological changes of the mouse organs were observed through pathological tissue sections,and the amount of the parasite in the liver,lung,kid-ney,and brain of the mice was detected by fluorescence quantitative PCR.The results showed that the survival time of the mice treated with lycorine was significantly extended,and the survival rate reached 80％.The spleen index of mice treated with lycorine was lower than that of the control group.Lycorine up-regulates the ratio of the CD4+T lymphocytes and NK cells in the spleen of mice infected with T.gondii,and helps to improve the ability of mice to resist T.gondii infection.Lycorine can up-regulate the levels of anti-inflammatory cytokine IL-4 and down-regulate the lev-els of pro-inflammatory factors IFN-γ,IL-1β,and IL-9 in serum of mice infected with T.gondii,which is conducive to reducing the damage of inflammatory response and enhancing the ability of anti-T.gondii infection.In addition,lycorine can alleviate the pathological damage of T.gondii to the liver,lungs,spleen,and kidneys of mice,and significantly reduce the amount of the parasite in the lung of mice.The results showed that lycorine could up-regulate the proportion of immune cells CD4+T lymphocytes and NK cells,inhibit the inflammatory response of mice infected with T.gondii,reduce the pathological damage of mice organs,and enhance the ability of mice to resist T.gondii infection,which is expected to become a novel anti-T.gondii drug.

Objective:To evaluate the feasibility of a novel flexible ultrasound imaging catheter for high-resolution real-time imaging of deep abdominal structures via percutaneous intervention.Methods:A self-developed flexible ultrasound catheter system（outer diameter：3.3 mm，integrated with a 10.5 MHz high-frequency linear array transducer and 4-degree-of-freedom active deflection）was used to image abdominal organs（liver，gallbladder，pancreas，etc.）in two healthy beagles via percutaneous puncture，with comparison to conventional surface convex array probes（3.6 MHz）. Image quality was assessed using a double-blind design，independently scored by five ultrasound physicians with over 10 years of experience on a 6-point scale. Mixed-effects ordinal logistic regression（adjusted for dog，organ，and evaluator variability）was employed for inter-group comparisons，with effect sizes quantified by Cliff's delta. Characteristic anatomical structure detection rates were analyzed using generalized linear mixed models（Firth correction for zero events）. Inter-rater reliability was assessed via intraclass correlation coefficient（ICC，two-way random model）and Kendall's coefficient of concordance.Results:The flexible catheter group demonstrated significantly superior image quality compared to the surface probe group . The most pronounced improvement was observed in adrenal imaging（5 points vs. 1 point， P<0.001，δ=0.92），while pancreatic imaging showed no significant difference（2 points vs. 2 points， P=0.812，δ=0.05）. Other organs exhibited significant quality enhancements（all P<0.05，δ=0.63～0.81）. The catheter significantly improved detection rates of characteristic structures：gastric wall stratification（90% vs. 10%， OR=36.0， P<0.001），adrenal corticomedullary differentiation（80% vs. 0， OR=∞， P<0.001），and gallbladder/small intestinal wall trilaminar structure（80% vs. 20%， OR=12.0， P=0.003）. The high-quality image rate（≥5 points）reached 77.8%，representing an 11.6-fold improvement over surface ultrasound（6.7%， P<0.001）. Inter-rater reliability was excellent（ICC=0.85，W=0.79）. Conclusions:Percutaneous flexible ultrasound catheter imaging significantly enhances resolution and anatomical detail visualization of deep abdominal structures. Combining minimally invasive access with operational flexibility，this technology shows promise for providing precise image guidance in minimally invasive procedures.

Anesthesia, General/adverse effects* ; Hypertension/etiology* ; Humans

Glycyrrizae Radix et Rhizoma has high medicinal value and is widely used in compatibility. It is used most frequently in the compatibility of Chinese medicine prescriptions，and is known as ''Guolao''（national medicine） and "master of all medicines". The characteristic active ingredients are mainly liquitin，glycyrrizic acid，glycyrrizin，and licochalcone. In different compatibilities，based on traditional and modern pharmacological theories，the corresponding effect of Glycyrrizae Radix et Rhizoma are brought into play through different mechanisms. Based on the traditional pharmacology of Glycyrrizae Radix et Rhizoma for tonifying spleen，replenishing Qi，clearing heat，removing toxin，dispelling phlegm，relieving cough and pain，and harmonizing various medicines，this paper used herbal authentication to analyze its compatibility application and mechanism. It was found that Glycyrrizae Radix et Rhizoma played corresponding effect in compatibilities through "tonification"，"harmonization"，and "regulation". For example，Glycyrrizae Radix et Rhizoma was combined with tonics including Ginseng Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma to tonify the five Zang-organs through its strong tonifying effect，combined with Paeoniae Radix Alba and Aconiti Lateralis Radix Praeparata to relieve emergencies and pains through harmonizing medicine power and properties，and combined with Rhei Radix et Rhizoma and Natrii Sulfas to reduce medicine intensity through regulating medicine properties and body characteristics. The application law and mechanism of the modern pharmacological compatibility of Glycyrrizae Radix et Rhizoma were analyzed by data mining and network pharmacology. It was found that the modern clinical formula was often compatible with Glycyrrizae Radix et Rhizoma for anti-inflammation，cardiovascular and cerebrovascular protection，anti-virus，and anti-tumor，Ephedrae Herba and Scutellariae Radix for anti-inflammation，Bambusae Caulis in Taenias，Salviae Miltiorrhizae Radix et Rhizoma，and Aurantii Fructus Immaturus for cardiovascular and cerebrovascular protection，and Ophiopogonis Radix and Chuanxiong Rhizoma for nerves protection. Meanwhile，the important targets of the characteristic ingredients were protein kinase B1 （Akt1），interleukin-6 （IL-6），tumor necrosis factor （TNF），and epidermal growth factor receptor （EGFR）. The important characteristic pathways such as tyrosine kinase inhibitor resistance pathway and cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG） signal pathway played the role of cardiovascular and cerebrovascular protection，and proteoglycan pathway in cancer played a neuroprotective role. This study is expected to provide references for the rational compatibility and application of Glycyrrizae Radix et Rhizoma，as well as the compatibility application of Chinese medicine prescriptions.

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.
Biomarkers, Tumor ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Kidney ; Kidney Neoplasms/genetics* ; Male ; Middle Aged ; Prognosis

Objective: To investigate the clinicopathological features, molecular characteristics, differential diagnosis and prognosis of anaplastic lymphoma kinase (ALK)-translocation renal cell carcinoma. Methods: Two cases of ALK-translocation renal cell carcinoma diagnosed from January 2011 to December 2020 were retrospectively analyzed to characterize their morphological features, immunohistochemical expression and prognosis. Multiple molecular studies including fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and next-generation sequencing were performed to characterize the genetic alterations. Results: Two patients included one male and one female, with 59 and 57 years old, respectively. Morphologically, case 1 resembled collecting duct carcinoma or renal medullary carcinoma, which demonstrated tubular, microcapsule and reticular structures, with a remarkable myxoid background and lymphocytes infiltration; case 2 resembled Xp11.2 translocation renal cell carcinoma or type 2 papillary renal cell carcinoma, which demonstrated tubular papillary and focal solid structures, with flocculent cytoplasm and many foamy histiocytes, but without myxoid background and lymphocytes infiltration. Immunohistochemistry showed strongly positive expression of ALK. CK7, E-cadherin, vimentin, PAX8 and CD10 showed various degrees of expression, and other antibodies were nonreactive. A variety of molecular assays showed definite ALK gene translocation, with rare VCL-ALK gene fusion (VCL exon and 16-ALK exon 20) in case 1, and EML4-ALK gene fusion (EML4 exon and 2-ALK exon 20) in case 2. Conclusions: ALK-translocation renal cell carcinoma is rare with various morphological features, and is easy to miss and misdiagnose. The characteristic ALK expression and molecular detection of ALK translocation are helpful for diagnosing this type of renal cell carcinoma.
Anaplastic Lymphoma Kinase/genetics* ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Kidney Neoplasms/genetics* ; Lung Neoplasms ; Male ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies

Objective: To investigate the immunohistochemical expression of NKX3.1 and NKX2.2 in mesenchymal chondrosarcoma (MC), and to explore the differential diagnostic value of NKX3.1 and NKX2.2 in MC and other types of small round cell malignant tumors. Methods: A total of 12 cases of MC and 97 other small round cell malignant tumors diagnosed in Jinling Hospital, Nanjing University School of Medicine from 2001 to 2020 were collected for NKX3.1 and NKX2.2 immunohistochemical detection. Among them, two kinds of NKX3.1 antibodies [rabbit polyclonal antibody and rabbit monoclonal antibody (EP356)] were used for detection in 12 cases of MC, and one NKX3.1 antibody (rabbit polyclonal antibody) was detected in 97 cases of other small round cell malignant tumors, and the relevant literature was reviewed. Results: The 12 MC patients included 7 females and 5 males, with a mean age of 33 years (14-54 years). Nine cases were from bone and three from soft tissue. Among the 12 MC patients, 8 patients had postoperative recurrence or metastasis, and 3 of them died of tumor recurrence or metastasis. Histologically, 12 cases of MC showed typical bidirectional differentiation.The positive rate of both NKX3.1 antibodies in MC was 12/12, NKX3.1 was focal weakly positive in only one of 12 chondrosarcomas (grade 3), 5 alveolar rhabdomyosarcomas, 5 embryonal rhabdomyosarcomas, and 5 solitary fibrous tumors, respectively. The remaining 70 cases of other small round cell malignant tumors were negative. The positive rates of NKX2.2 in MC, Ewing sarcoma and olfactory neuroblastoma were 12/12, 15/15 and 4/5, respectively. In 12 cases of chondrosarcoma (grade 3), 5 cases of poorly differentiated synovial sarcoma, 5 cases of alveolar rhabdomyosarcoma, and 5 cases of solitary fibrous tumor, NKX2.2 was focally and weakly positive in only one case, respectively, and all the remaining 50 cases of other small round cell malignant tumors were negative. Conclusions: The expression of NKX3.1 and NKX2.2 proteins are significant indicators in the diagnosis of MC, and the combined detection of NKX3.1 and NKX2.2 can help distinguish MC from most other small round cell malignant tumors.
Biomarkers, Tumor ; Chondrosarcoma, Mesenchymal/diagnosis* ; Diagnosis, Differential ; Female ; Homeodomain Proteins ; Humans ; Immunohistochemistry ; Male ; Nuclear Proteins