Objective:To assess the long-term outcome of sequential radical surgery after immune combined with targeted therapy for patients with initially unresectable hepatocellular carcinoma (HCC).Methods:Clinical data of 100 patients with initially unresectable HCC undergoing sequential radical surgery after immune combined with targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital from December 2018 to August 2023 were prospectively collected, including 87 males and 13 females, with a median age of 55 (24-73) years. The pre-treatment tumor staging was determined using the China liver cancer staging (CNLC). The efficacy of immune combined with targeted therapy was accessed using the modified response evaluation criteria in solid tumor (mRECIST). The cycles of immune combined with targeted therapy were analyzed. The tumor residual of resected tissue was analyzed through a standard pathological protocol. The prognosis was analyzed using the Kaplan-Meier method.Results:Upon initial diagnosis, there were 46 cases (46.0%) staged CNLC-Ⅲa and 40 (40.0%) staged CNLC-Ⅲb. There were also 14 cases (14.0%) staged CNLC-Ⅰb, Ⅱa, and Ⅱb who underwent immune combined with targeted therapy due to rupture of tumor or insufficient liver remnant. All patients received a median of 5 (3-28) cycles of immune combined with targeted therapy and underwent radical surgery after successful conversion. According to mRECIST, 14 (14.0%) were determined as complete remission, 63 (63.0%) as partial remission, 18 (18.0%) as stable disease, and 5 (5.0%) as disease progression. Of 24 (24.0%) were defined as pathologically complete remission by postoperative pathology. Furthermore, pathological tumor residue was less than 10% in 61 (61.0%) cases and less than 50% in 82 (82.0%) cases. The 1, 3, and 5 year-overall survival rates of patients were 98.0%, 83.1%, and 74.5%, respectively. The 1, 2 and 3 year-recurrence-free survival rates were 67.5%, 54.8%, and 49.6%, respectively.Conclusion:Sequential radical surgery after immune combined with targeted therapy benefits the long-term survival of patients with initially unresectable HCC.

Objective:To explore the clinicopathological and molecular genetic features of adult hepatic mesenchymal hamartoma (MHL).Methods:A total of five confirmed adult MHL cases diagnosed at the Pathology Department of the First Medical Center of the People's Liberation Army General Hospital between 2009 and 2022 were collected. Histomorphological observation and immunohistochemical staining were conducted. Gene detection was performed by next-generation sequencing.Results:Among the five cases, four were male and one was female, aged 46-67 years, with an average age of 56.2 years. The maximum diameter was 5.3-13.5cm, and the average diameter was 9.2cm. Tumors were generally cystic, solid, or mixed cystic-solid. Histopathologically, in four out of five cases of MHL, malignant transformation occurred, of which three cases were malignantly transformed into undifferentiated embryonal sarcoma and one case was malignantly transformed into a malignant solitary fibrous tumor. NAB2-STAT6 gene rearrangements were identified.Conclusion:Adult MHL is a rare kind of tumor with malignant potential, and it is difficult to diagnose with preoperative imaging examinations. A fine-needle biopsy is rarely used for diagnosis, but surgical resection of symptomatic or enlarged lesions is recommended to rule out the possibility of malignancy and further diagnosis. Genetic testing results revealed the complex genetic alterations in MHL, and it was found that adult MHL can malignantly transform into malignant solitary fibrous tumors. We believe that genome-wide analysis is necessary to determine the unique molecular characteristics of MHL and identify potential targets for therapeutic intervention.

Objective To explore the feasibility of minimally invasive autopsy by natural orifice transluminal endoscopic surgery.Methods Autopsy was performed on a deceased patient with COVID-19 via transesophageal,transtrachea,and transgastric natural orifice transluminal endoscopic surgery.The white light endoscopic manifestations of the corresponding organs were observed,and organ tissue specimens were obtained for routine pathological examination.Results All four pathways reached the corresponding organs successfully.Diffuse congestion and submucous bleeding were seen in the trachea,bronchus and bronchus of the pulmonary lobes.The bronchus of the left lower lobe was filled with dark red sputum;the surface of the left lung was congested obviously.Four thrombi and plaque rupture were seen on the aortic wall.The gastric mucosa was congested,eroded,and had active ulcers.The surface of heart and liver was smooth.Small lamellar panniculitis was seen in the omentum.Routine pathology showed chronic inflammation with acute inflammation of the bronchial mucosa and inflammatory exudation,and partial squamous metaplasia of the epithelium.In lung tissue,some alveolar epithelial hyperplasia,a little fibrin-like exudation,widened alveolar septa,and infiltration of acute and chronic inflammatory cells were seen.The columnar epithelial mucosa of the gastric mucosa showed chronic inflammation with acute inflammation and exudates and fungal masses.Conclusion Natural orifice transluminal endoscopic surgery is feasible for autopsy,and covid-19 virus can cause multi-system and multi-organ damage.

Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.

Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.

Objective: To construct the key elements of mental care program for cancer patients based on Swanson′s caring theory. Methods: Based on Swanson′s caring theory, using expert group discussion and Delphi expert inquiry, screening indicators to establish psychosocial care program for cancer patients. Results: The effective recovery rates of the two rounds of expert inquiries were 100% (34/34) and 94.12% (32/34), respectively. The coefficient of authority of experts was 0.89, and the coefficient of coordination of expert opinions was 0.411. The final training system includes five first-level indicators, 17 second-level indicators and 89 third-level indicators. Conclusion The mental care program can provide reference for clinical practice.

OBJECTIVE： To establish content determination method for simultaneously determining aucubin，geniposidic acid，catechin，chlorogenic acid，asperuloside，rutin，isoquercitrin and astragalin in Eucommia ulmoides leaves. METHODS：HPLC method was adopted. The determination was performed on Agilent ZORBAX SB-C18 column with the mobile phase consisted of acetonitrile-0.1％ phosphoric acid（gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was set at 203 nm for aucubin and catechin，239 nm for geniposidic acid and asperuloside，220 nm for chlorogenic acid，354 nm for rutin and isoquercitrin，and 266 nm for astragalin. The sample size was 5 μL. RESULTS： The linear range of aucubin， geniposidic acid， catechin， chlorogenic acid， asperuloside， rutin， isoquercitrin and astragalin were 0.812-6.090 μg（r＝0.999 3），0.438-3.285 μg（r＝0.999 2），0.045-0.336 μg（r＝0.999 2），0.882-6.615 μg（r＝0.999 3），0.097-0.726 μg（r＝0.999 1），0.064-0.483 μg（r＝0.999 3），0.048-0.360 μg（r＝0.999 1） and 0.014-0.108 μg（r＝0.999 7），respectively. RSDs of precision， stability and reproducibility tests were all lower than 3.5％（n＝6）. The average recovery rates were 101.60％，103.06％，99.77％，96.93％，98.17％，96.75％，98.97％ and 99.60％，with RSDs of 1.42％，2.65％，2.78％，2.05％，2.26％，0.93％，2.79％ and 3.08％，respectively（n＝6）. The contents of aucubin， geniposide， catechin， chlorogenic acid， plantain， rutin， isoquercetin and astragaloside in 12 batches of E. ulmoides leaves from different collection time and planting varieties were 10.903-17.245， 5.578-7.892， 0.198-0.440， 13.890-19.782， 1.008-1.547， 1.102-2.396， 0.267-0.701， 0.150-0.412 mg/g， respectively. The content fluctuated greatly. The contents of aucubin， geniposide， catechin， chlorogenic acid， rutin and pinoresinol diglucoside in cortex of E. ulmoides were 0.299， 0.123， 0.580， 0.112， 0.026，1.961 mg/g， respectively. CONCLUSIONS： The method is simple， reproducible and accurate. It can be used to evaluate the quality of E. ulmoides leaves. There are obvious differences in composition and content of components in different medicinal parts （cortex， leaves） of E. ulmoides.

Objective: To explore the value of CT texture analysis (CTTA) in differentiating the pathological grade of urothelial carcinoma of the bladder (UCB). Methods: A total of 53 lesions from 43 patients with bladder cancer confirmed by postoperative pathology were retrospectively analyzed, including 27 cases of high-grade urothelial carcinoma (HGUC) and 26 cases of low-grade urothelial carcinoma (LGUC). All the patients took pelvic CT and enhanced scanning in the same CT scanner with same scanning parameters. Lesions on both plain and enhanced CT images were delineated on software by two radiologists to extract the corresponding volumes of interest (VOI) and then 92 parameters based on feature classes were generated. The average values of two radiologists were obtained. The difference parameters between HGUC group and LGUC group were screened by nonparametric test, and the receiver operating characteristic (ROC) was drawn. The corresponding optimal thresholds were determined and diagnostic effect was assessed. Results: Nine difference texture parameters between HGUC group and LGUC group were selected, including 5 parameters on unenhanced images, namely, skewness, root mean squared, cluster shade, zone percentage and large area high gray level emphasis. There were 4 parameters on enhanced images, namely, skewness, kurtosis, cluster shade and zone percentage. The largest area under curve of 0.840±0.058 (95% CI 0.726-0.955) was obtained from skewness generated by VOI of unenhanced images. The cut-off value of skewness was 0.186 5, which permitted the diagnosis of HGUC with sensitivity of 92.59%, specificity of 73.08%, positive predictive value of 78.13%, negative predictive value of 90.48% and accuracy of 83.02%. Conclusion CTTA can effectively distinguish between LGUC and HGUC. Skewness from unenhanced CT images had the optimal diagnostic performance.

The aim of this paper was to investigate the absorption mechanism of silybin(SLB)in Caco-2 cells. Concentrations of samples in the study were determined by developing LC/MS/MS method of SLB, propranolol and atenolol in HBSS buffer to calculate apparent permeability coefficient(Papp). When Caco-2 cells were cultured to the 21st day, the TEER were above 350 Ω ·cm2. The Papp of Lucifer yellow was far less than 1 × 10-7 cm/s. As the positive control drugs, The Papp of atenolol and propranolol were similar to those reported in the literature, indicating that the Caco-2 monolayer model was successfully established in this experiment. The Papp(AP-BL) of SLB at 5, 20, and 50 μg/mL were all more than 2×10-6 cm/s, which showed that SLB was a moderately permeable drug. The efflux ratio was greater than 2 indicating the efflux transporter may be involved in the absorption process of SLB. The Papp of silybin-N-meglumine was similar to that of SLB, suggesting that salt formation did not alter the membrane permeability of SLB. In conclusion, the membrane permeability of SLB is good, and its solubility is low. SLB is a BCS class 2 drug. The release of SLB in the gastrointestinal tract is an important factor in its absorption process.

To investigate the effect of combination of schisandrin B and doxorubicin on the pharmacokinetic behavior of doxorubicin in SD rats. An LC-MS/MS method was established for the determination of doxorubicin and its main metabolite doxorubicinol in SD rats plasma. Separation was performed on Agilent Eclipse XDB-C18 column(100 mm×2. 1 mm, 3. 5 μm)using 0. 1% formic acid solution and acetonitrile as mobile phase with a liner gradient program. The ion transitions were performed under ESI position model at m/z 544. 2→397. 3(doxorubicin), m/z 546. 2→399. 2(doxorubicinol), m/z 528. 2→381. 2(daunorubicin, internal standard). Calibration curves of doxorubicin(0. 500-500 ng/mL)and doxorubicinol(0. 200-50. 0 ng/mL)showed good linear regression. The precision and accuracy met the requirements. The variation coefficient of extraction recovery and matrix effect was less than 15%. The AUC0-t of doxorubicin were(605. 69±145. 84)and(564. 53±23. 99)ng ·h/mL in alone and combined group, respectively. The AUC0-t of doxorubicinol were(26. 69±13. 41)and(29. 00±2. 78)ng ·h/mL, respectively. Results indicated that, schisandrin B had not affected the pharmacokinetic behavior of doxorubicin in SD rats.