The clinical data of 10 patients with pathologically confirmed primary hepatic neuroendocrine neoplasms (PHNENs) were retrospectively analyzed. The cohort included 8 males and 2 females, with a median age of 63 years. None presented with carcinoid syndrome. Three cases were detected incidentally during health check-ups, 2 presented with painless jaundice, and 5 reported abdominal distension or pain (1 with concurrent jaundice). Elevated tumor markers included carbohydrate antigen 19-9 in 4 cases, alpha-fetoprotein in 2 cases, and neuron-specific enolase in 1 case. All patients underwent surgical resection, including hepatectomy and hilar cholangiocarcinoma resection, combining with resection and reconstruction of right hepatic artery, resection of liver metastases and pancreaticoduodenectomy according to the extent of tumor invasion.Preoperative imaging failed to diagnose neuroendocrine neoplasms in all cases. Final pathological diagnoses were neuroendocrine tumor (NET) G2 in 5 cases, NET G3 in 1 case, and neuroendocrine carcinoma (NEC) in 4 cases. During the follow-up, 4 patients died and 6 survived. The study demonstrates that PHNENs lack specific clinical or imaging features, and the diagnosis relies on pathological examination after excluding metastatic disease. Radical resection remains the primary treatment, with prognosis varying significantly by tumor grade.
Humans ; Middle Aged ; Male ; Female ; Neuroendocrine Tumors/pathology* ; Liver Neoplasms/pathology* ; Retrospective Studies ; Aged ; Adult

Objective:To detect the expressions of S100P, mucin 5A, mucin 6, estrogen-inducing protein pS2, C-reactive protein (CRP), N-cadherin and CD56 in intrahepatic cholangiocarcinoma (ICC) and to analyze the sensitivity and specificity in the diagnosis of large and small bile duct cholangiocarcinoma.Methods:Clinical data of 47 patients (22 patients small bile duct and 25 patients large bile duct ICC) diagnosed with ICC at Ningbo Clinical Pathology Diagnosis Center from January 2018 to September 2019 were retrospectively analyzed, including 29 males and 18 females, aged (64.0±11.1) years. Cancer tissue specimens were collected. The expressions of S100P, mucin 5A, mucin 6, estrogen-induced protein pS2, CRP, N-cadherin and CD56 in cancer tissues were detected by immunohistochemical method, and the sensitivity and specificity of these proteins in the diagnosis of small bile duct and large bile duct ICC were analyzed.Results:In 22 patients with small bile duct type ICC, CD56 expression was positive in 12 (54.5%), CRP expression in 22 (100.0%) and N-cadherin expression in 21 (95.5%), large bile duct type ICC were 8.0%(2/25), 28.0%(7/25), 40.0%(10/25). In 25 cases of large bile duct type ICC, S100 calcium-binding protein P expression was positive in 23 cases (92.0%), estrogen-induced protein pS2 expression in 21 (84.0%) and mucin 5A expression in 23 (92.0%), small bile duct type ICC were 9.1%(2/22), 36.4%(8/22), 0. The positive expression rates of CD56, CRP and N-cadherin in small bile duct type ICC were significantly higher than those in large bile duct type ICC, while S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A were lower than those in large bile duct type ICC (all P<0.05). The sensitivity of CD56, CRP and N-cadherin in the diagnosis of small bile duct type ICC were 54.5%, 100.0% and 95.5%, and the specificity were 92.0%, 72.0% and 60.0%, respectively. The sensitivity of S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A in the diagnosis of large bile duct type ICC were 92.0%, 84.0% and 92.0%, and the specificity were 90.9%, 63.6% and 100.0%, respectively. Conclusion:The positive expressions of CD56, CRP, N-cadherin, S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A are of great value in the differential diagnosis of large bile duct type and small bile duct type ICC, and the diagnostic accuracy is reasonable, which could facilitate the accurate histological classification of ICC.

Objective:To compare the prognosis of patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV)-associated ICC after radical resection.Methods:The clinicopathological and survival data of 69 patients with ICC undergoing radical resection in the Department of Hepatobiliary and Pancreatic Surgery, Lihuili Hospital Affiliated to Ningbo University from January 2012 to February 2024 were retrospectively analyzed, including 40 males and 29 females, aged (62.9±10.2) years. Patients were divided into the stone group ( n=40, with hepatolithiasis) and HBV group ( n=29, with HBV). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison. Cox proportional hazard regression model was used for multivariate analysis to analyze the effect of hepatolithiasis and HBV on the prognosis. Results:The median overall survival of ICC patients in the stone group was 16 months, and that in the HBV group was 27 months. The 1-, 3-, and 5-year cumulative survivals of the stone group were 56.6%, 23.2%, and 10.3%, respectively, which were lower than those of the HBV group (72.0%, 50.7%, and 43.4%, respectively, χ2=5.95, P=0.015). The median recurrence-free survivals (RFS) of the stone group and the HBV group were 12 months and 23 months, respectively. The 1-year and 3-year RFS of the stone group were 49.2% and 18.1%, which were lower than those of the HBV group (65.0% and 39.8%, respectively, χ2=3.94, P=0.047). Univariate analysis showed that hepatolithiasis was assciated with prognosis ( χ2=5.95, P=0.015). Multivariate Cox regression analysis showed that hepatolithiasis and hepatitis B virus infection had no effect on the prognosis of ICC patients after surgery (all P>0.05). Conclusion:Compared to HBV infection, ICC patients with hepatolithiasis have a worse prognosis. Hepatolithiasis and HBV infection have no effect on the prognosis of ICC after radical resection.

Objective:To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment.Methods:A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples.Results:The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor′s surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34βE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC ( P=0.002), TP63 ( P=0.002), CDKN1C ( P=0.002) and NFE2L2 ( P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway ( P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway ( P=0.013) and PI3K pathway ( P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion:Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.

Objective:To analyze the correlation between the histological classification of hepatocellular carcinoma (HCC), especially macrotrabecular-massive (MTM), tumor invasiveness, and prognosis.Methods:The clinical and follow-up data of 246 consecutive HCC cases who met the inclusion criteria from 2015 to 2018 were retrospectively analyzed. They were divided into trabecular/pseudoglandular, trabecular/patchy, and MTM types according to the histological classification. The relationship between each type and related clinicopathological features was analyzed. The Kaplan-Meier method was used to plot tumor-free survival (DFS) and overall survival (OS) curves. Log rank tests, COX univariate, and multivariate regression analyses were conducted to analyze the relationship between clinical features, including histological classification, DFS, and OS.Results:Trabecular/pseudoglandular, trabecular/nodular, and MTM type proportions were 44.7% (110 cases), 32.9% (81 cases), and 22.4% (55 cases), respectively. The results of the clinicopathological features showed that MTM-type HCC was significantly more invasive than the other two types, with alpha-fetoprotein (AFP) ≥400 ng/ml, tumor diameter≥8 cm, no tumor capsule, poor differentiation, and MVI positivity proportions, and the differences were statistically significant (P < 0.05).The proportion of MTM-type HCC patients with American Joint Committee on Cancer TNM Stage III to IV and Chinese Liver Cancer Staging (CNLC) II to II was significantly higher than that of the first two types, and the differences were statistically significant (P < 0.05). In addition, the proportion of MTM subtypes undergoing transcatheter arterial chemoembolization was also raised (P < 0.05). The DFS and OS were significantly lower for MTM-type HCC compared to trabecular/pseudoductal-type HCC at 1-, 3-, and 5-years, and the differences were statistically significant (P < 0.05). Univariate analysis indicated that strongly invasive clinical pathological features such as alpha fetoprotein (AFP) ≥400 ng/ml, tumor diameter ≥ 8 cm, no tumor capsule, poor differentiation, positive microvascular invasion, tumor stage, and MTM staging were all risk factors affecting DFS and OS (P < 0.05). Multivariate COX analysis showed that MTM histological staging, AFP ≥ 400 ng/ml, tumor non-encapsulation, satellite nodules, CNLC stages II~III, and TNM stages III~IV were independent risk factors for DFS (P < 0.05), while AFP ≥ 400 ng/ml, tumor non-encapsulation, and CNLC stage II~III were independent risk factors for OS ( P < 0.05).Conclusion:Histological classification is highly correlated with tumor invasiveness and HCC prognosis. Trabecular/pseudoglandular types have lower malignancy and a better prognosis, while MTM types exhibit strong invasive features and a poor prognosis.

Objective:To investigate the clinical, endoscopic and pathological features, and treatment and prognosis of gastric adenocarcinoma of fundic gland type of chief cell predominant type (GA-FG-CCP).Methods:Data of 40 GA-FG-CCP patients with 41 lesions diagnosed by histopathology at Ningbo Medical Center Lihuili Hospital and Shanghai East Hospital from January 2018 to May 2023 were collected. Their clinical and endoscopic features, pathological features, immunohistochemical results, endoscopic treatment, and prognosis were analyzed.Results:Among the 40 GA-FG-CCP patients, there were 15 males and 25 females, and the mean age was 60.03 years. Most of them had no obvious clinical symptoms or family history of tumor. Except one case, others had no helicobacter pylori infection. The endoscopic features of white light observation were: ① the main location was the upper part of the gastric body (63.41%, 26/41); ② faded or whitish mucosal surface (56.10%, 23/41); ③ dilated vessels with branch architecture (78.05%, 32/41); ④ no background mucosal atrophy (100.00%, 41/41). The features of magnifying endoscopy with narrow band imaging (ME-NBI) were: ① no obvious demarcation line (85.37%, 35/41); ② enlargement of the crypt opening (87.80%, 36/41); ③ widening of the intervening part (92.68%, 38/41); ④ lack of irregular microvascular pattern (95.12%, 39/41). All patients were confirmed gastric adenocarcinoma of the fundic gland by biopsy. The glands showed a low degree of dysplasia, similar to the differentiation of chief cell predominant pattern, also with scattered parietal cells, forming irregular and anastomosing cords. In the 40 patients, 20 did not receive endoscopic therapy. Twelve out of 21 lesions in 20 cases treated with endoscopic resection infiltrated into the submucosa (20-520 μm), 9 cases were intramucosal carcinoma. There was no lymphatic or venous infiltration, and horizontal and vertical margins were negative. Immunohistochemical staining results showed that the tumor was postive for pepsinogen-Ⅰ and MUC 6, with scattered postive for H +-K +-ATPase, but negative for MUC5AC, MUC2 and CD10, and the Ki-67 labeling index was low. No patients had recurrence or metastasis during mean follow-up of 15.85 months. Conclusion:GA-FG-CCP is rare and very well differentiated. Its clinical symptoms are not obvious, but there is endoscopic characteristics. The detection rate of GA-FG-CCP can be improved by white light and ME-NBI, and the diagnosis can be confirmed by pathology and immunohistochemical staining.

Objective To synthesize and investigate cytotoxicity of an indole-chalcone derivative FC58. Methods The target compound was synthesized through the Aldol condensation with 1-(3,4,5-trimethoxyphenyl)ethan-1-one and 1H-indole-3-carbaldehyde. The Cell Titer-Blue method was used to determine in vitro cytotoxicity. The cell cycle experiment was performed to analyze the action characteristics of FC58. Results FC58 exhibited high cytotoxicity against various leukemia cells and resulted in G2/M phase arrest. It showed stronger drug resistant index than traditional tubulin inhibitors such as paclitaxel, vinblastine and doxorubicin. Conclusion FC58 represents a promising lead compound for multi-drug resistant leukemia.

Objective:To study the relationship between morphologic classification and prognosis of patients with intrahepatic cholangiocarcinoma (ICC).Methods:The clinicopathologic data of 125 ICC patients who underwent R 0 resection at the Ningbo Medical Center Li Huili Hospital from January 2011 to May 2019 were retrospectively analyzed. This cohort consisted of 67 males and 58 females, aged 26.0 to 82.0 (63.5±9.5) years old. Based on the resected specimens, the patients were divided into the mass forming type, periductal infiltrating type and mixed type. The survival rates and recurrence-free survival outcomes of the patients among the three types were compared, and the risk factors that influenced prognosis were analyzed. Results:Using the predetermined inclusion and exclusion criteria, 16 patients with missing data and other causes of death were excluded from the initial 125 patients. Also, as the number of the mixed type was small, these patients were excluded. Finally 62 patients in the mass forming type and 42 patients in the periductal infiltrating type were analyzed. In the mass forming group, there were 32 males and 30 females, aged (63.1±9.1) years. In the perivascular infiltration group, there were 22 males and 20 females, aged (64.1±10.2) years. The 1-, 3-, 5-year survival rates of the mass forming group were 78.1%, 33.2%, 18.9% (median survival 25 months). The 1-, 3-, 5-year survival rates of the periductal infiltrating type were 63.3%, 8.3%, 6.1% (median survival 15 months). There were statistically significant differences between the two groups ( P<0.05). The median recurrence-free survival for the mass forming and the periductal infiltrating groups were 18 and 11 months, respectively, with a statistically significant differences between them ( P<0.05). Univariate and multivariate analysis showed that TNM staging Ⅲ~Ⅳ ( HR=2.966, 95% CI: 1.549-5.679) and periductal infiltrating type ( HR=2.403, 95% CI: 1.236-4.670) were independent risk factors for survival of these patients after operations. TNM staging Ⅲ~Ⅳ ( HR=2.466, 95% CI: 1.325-4.589), low grade differentiation ( HR=0.528, 95% CI: 0.299-0.934) and periductal infiltrating type ( HR=2.432, 95% CI: 1.295-4.565) were independent risk factors for relapse-free survival of these patients ( P<0.05). Conclusions:Morphological classification was found to be an independent risk factor for prognosis of ICC patients in this study, with significantly worse long-term prognosis when compared with the mass forming type.

Coronavirus infection seriously threatens human health. There is no specific medication or vaccine so far. In recent years, domestic and foreign researchers have developed a variety of small-molecule inhibitors against the ligand S protein, RdRp, PL^pro and 3CL^pro of three highly pathogenic coronavirus, SARS-CoV，MERS-CoV，SARS-CoV-2. This article reviews the characteristics of these coronaviruses, action targets, small molecule inhibitors, and structure-activity relationships.

Scutellaria baicalensis (S. baicalensis) and Scutellaria barbata (S. barbata) are common medicinal plants of the Lamiaceae family. Both produce specific flavonoid compounds, including baicalein, scutellarein, norwogonin, and wogonin, as well as their glycosides, which exhibit antioxidant and antitumor activities. Here, we report chromosome-level genome assemblies of S. baicalensis and S. barbata with quantitative chromosomal variation (2n = 18 and 2n = 26, respectively). The divergence of S. baicalensis and S. barbata occurred far earlier than previously reported, and a whole-genome duplication (WGD) event was identified. The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement. Comparative genome analysis of the congeneric species revealed the species-specific evolution of chrysin and apigenin biosynthetic genes, such as the S. baicalensis-specific tandem duplication of genes encoding phenylalanine ammonia lyase and chalcone synthase, and the S. barbata-specific duplication of genes encoding 4-CoA ligase. In addition, the paralogous duplication, colinearity, and expression diversity of CYP82D subfamily members revealed the functional divergence of genes encoding flavone hydroxylase between S. baicalensis and S. barbata. Analyzing these Scutellaria genomes reveals the common and species-specific evolution of flavone biosynthetic genes. Thus, these findings would facilitate the development of molecular breeding and studies of biosynthesis and regulation of bioactive compounds.
Evolution, Molecular ; Flavonoids/biosynthesis* ; Genome, Plant ; Plant Extracts/genetics* ; Scutellaria/metabolism* ; Whole Genome Sequencing