Objective:To assess the safety and efficacy of induction chemotherapy with cisplatin and docetaxel followed by radia-tion concurrent with weekly cisplatin for unresectable, locally advanced esophageal cancer. Methods: Thirty-three patients with T3N0M0 to T4N2M0 thoracic esophageal squamous cell carcinoma without celiac lymph node metastasis were included in the study. They were treated with cisplatin (75 mg/m2 d1, d22) and docetaxel (75 mg/m2 d1, d22) neoadjuvant chemotherapy followed by three-dimensional conformal radiotherapy (60Gy/30F/6w) concurrent with cisplatin (30 mg/m2 d1, 8, 15, 22, 29, 36 from the beginning of radiation). Results:Grade 4 hematological toxicities were observed in 13.33%(4/33) of the patients after the neoadjuvant chemother-apy. No grade 3 or above hepatic or renal toxicities were found. During concurrent chemoradiation, the highest grade 3 hematological toxicities were observed in the erythrocyte, granulocyte, and macrophage at 21.21%(7/33), 15.15%(5/33), and 3.01%(1/33), respec-tively. No grade 2 or above hepatic or renal toxicities were observed. Grade 3 radiation esophagitis was observed in 9.1%(3/33) of the patients, whereas grade 3 and above radiation esophagitis or grade 1 and above acute radiation pneumonitis did not occur. The evalua-tion results after treatment completion were 84.85%(28/33), 12.12%(4/33), and 3.03%(1/33) for CR+PR, SD, and PD , respectively. Two months after treatment completion, the results changed to 75.76%(25/33), 9.10%(3/33), and 15.15%(5/33), respectively. Overall, 15 patients died. The one-year survival rate was 66.4%. Local failure was approximately 46.67%(7/15), whereas the local+distant fail-ure was approximately 26.67%(4/15). Therefore, local failure is the main pattern of failure in esophageal cancer. Conclusion:The re-sults indicate that neoadjuvant chemotherapy with cisplatin and docetaxel followed by radiotherapy concurrent with weekly cisplatin for locally advanced esophageal cancer is safe. Local failure remains the main pattern of failure in esophageal cancer.

Objective To investigate the clinical value of serum metabonomic profile of pancreatic cancer using nuclear magnetic resonance (NMR)-based metabonomics.Methods The retrospective case-control study was adopted.The clinical data of 23 patients with pancreatic cancer (PC group) and 16 healthy volunteers (control group) who were admitted to the Fujian Medical University Union Hospital between December 2013 and December 2014 were collected.The serum of the 2 groups was measured by 1H NMR spectroscopy.Multivariate statistical analyses were performed to identify the characteristic metabolites in the 2 groups,including principal component analysis (PCA),partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA).Observation indicators included:(1) multivariate statistical analysis of serum metabonomic profile,results of PCA,PLS-DA and OPLS-DA,(2) screening of metabolites.Measurement data with normal distribution were presented as x ± s.The comparison between groups was evaluated with the t test.The count data were analyzed using the chi-square test.Results (1) The multivariate statistical analysis of serum metabonomic profile:results of PCA showed that expression rates of principal component 1 (PC1) and principal component 2 (PC2) to original data were 54.9％ and 23.5％,with both cumulative contribution rate of 78.4％.Results of PLS-DA showed that the separative trend between PC group and control group was appeared,and variance of X and Y matrixes and predictive value were 0.254,0.816 and 0.385.Results of OPLS-DA showed that the differences of samples between the 2 groups were further increased,and differential metabolites were screened according to the distinction of scores between the 2 groups,value of R2X,R2Y and Q2 was 0.254,0.816 and 0.433.(2) Screening of metabolites:35 serum metabolites were detected in the 2 groups.Compared with the control group,levels of 3-hydroxybuyarate,citrate,formate,glutamate,isoleucine,methionine and phenylalanine in the PC group were elevated (r =0.524,0.511,0.656,0.566,0.503,0.498,0.648,P ＜0.05),and levels of 3-methylhistidine,alanine,glutamine,LDL and VLDL in the PC group were decreased (r =-0.607,-0.508,-0.560,-0.568,-0.559,P ＜ 0.05).Conclusions Compared with healthy controls,several amino acids,citrate and lipoproteins demonstrate the metabolic differences in the serum of patients with pancreatic cancer.NMR based metabonomic profile technology can distinguish the difference of serum metabolites between patients with pancreatic cancer and healthy controls.NMR based metabonomic technology may be a promising method for the diagnosis of pancreatic cancer.

Objective:To investigate the application value of dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death for hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of a male 46-year-old patient with HCC who underwent dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death at the West China Hospital of Sichuan University in October 2019 were collected. He weighed 66 kg and was 171 cm in height. His blood type was A Rh-positive. Graft one was from a female 23-year-old living donor who had a bodyweight of 50 kg, a height of 150 cm, and blood type of A Rh-positive; graft two was from a male 44-year-old brain death donor with the blood type of A Rh-positive. The surgery was performed in three operating rooms, graft one and graft two were obtained simultaneously in two operating rooms, and the recipient′s liver was dissected in the third operating room. When the in vitro splicing of the liver was almost completed, surgeons entirely removed the recipient′s liver and started to transplant the new one. Observation indicators: (1) surgical situations and postoperative recovery of the living donor and the recipient; (2) postoperative pathological examination of the recipient′s liver; (3) follow-up. Follow-up was conducted by outpatient examinations, including monitoring of HCC recurrence, monitoring of new liver function, monitoring and adjustment of immunosuppressive agents, detection of biliary vascular complications, rejection and adverse drug reactions. Regular lifelong follow-up was required for recipients, with the latest follow-up on December 4, 2019. Count data were expressed as absolute numbers or percentages.Results:(1) Surgical situations and postoperative recovery of the living donor and the recipient: operation time, volume of intraoperative blood loss, volume of intraoperative infusion of autologous blood of the living donor were 315 minutes, 200 mL, 200 mL, respectively. The living donor was discharged from hospital on the sixth day after surgery without any complications. The recipient underwent modified piggyback liver transplantation successfully. Graft one was from the right segment free of the middle hepatic vein in the living donor, with a weight of 410 g. Graft two was from the left lateral segment in the donor after brain death, with a weight of 400 g. The graft from donors to recipient weight ratio was 1.2% after splicing. The operation time, duration of anhepatic phase, volume of intraoperative blood loss, volume of intraoperative blood transfusion were 815 minutes, 60 minutes, 1 500 mL, 1 800 mL, respectively. The recipient′s temperature was normal during hospitalization. On the first postoperative day, the level of white blood cell and neutrophilic granulocyte percentage of the recipient reached a peak (17.15×10 9/L and 91.7%, respectively) and then gradually decreased. After anti-infective treatment with piperacillin sodium and sulbactam sodium, both of the two indicators returned to normal on the seventh day after surgery (7.90×10 9/L and 70.9%, respectively), and the antibiotic was discontinued. During the hospitalization, the level of albumin of the recipient fluctuated in 31.0-41.4 g/L, the liver function parameters including total bilirubin, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international normalized ratio gradually returned to normal levels, and the renal function parameters including creatinine and estimated glomerular filtration rate remained within the normal range. On the tenth day after surgery, the recipient was in good condition and discharged from the hospital. (2) Postoperative pathological examination of the recipient′s liver: ① results of the pathological examination showed moderately differentiated HCC with incomplete tumour capsule and no invasion of the liver capsule. The surrounding liver tissues showed hepatitis B-related nodular cirrhosis, and no tumor involvement was detected at the broken end of the hilum. ② The gallbladder presented chronic cholecystitis accompanied by cholesterol deposition, and one abdominal lymph node showed reactive hyperplasia. The immunohistochemical staining showed 10% positive HBsAg and negative HBcAg. (3) Follow-up: the tumor markers of the recipient were tested on November 19, 2019, including α-fetoprotein (2.92 μg/L) and abnormal prothrombin (16 AU/L). Together with the negative result of abdominal colour doppler ultrasound, they collectively indicated no HCC recurrence in the recipient. The liver function parameters including total bilirubin (8.6 μmol/L), alanine aminotransferase (23 IU/L), aspartate aminotransferase (28 IU/L) and albumin (44.0 g/L) of the recipient tested on December 3, 2019, were all in normal levels. Blood concentration of tacrolimus was 4.2 μg/L . The drug dose of mycophenolate mofetil dispersible tablets was adjusted to 250 mg given twice daily, and the drug dose of others was unchanged (tacrolimus 2 mg, once daily; sirolimus 1mg, once daily). No symptoms, signs or examination results indicated biliary vascular complications, rejection or adverse drug reactions. Conclusion:Dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death is safe and effective, which can be used as a suboptimal treatment for patients with HCC beyond Milan criteria.

Objective:To observe the expression, correlation and significance of chemokine (C-X-C motif) ligand 12 (CXCL12) and chemokine (C-X-C motif) receptor 4 (CXCR4) in endometrium and myometrium of adenomyosis.Methods:Totally 38 patients were selected in this study, who underwent hysterectomy for adenomyosis at Beijing Obstetrics and Gynecology Hospital from October 2017 to December 2018 as the adenomyosis group, and, in the same period, selected 31 patients with cervical intraepithelial neoplasia Ⅲ or cervical cancer undergoing hysterectomy served as control group. The expression levels of mRNA and protein for CXCL12, CXCR4 in the endometrium and myometrium of the two groups were detected by immunohistochemistry and real-time PCR.Results:(1) The protein levels of CXCL12 and CXCR4 in endometrium in uterus with adenomyosis (0.229±0.025 and 0.226±0.016) were significantly higher than those in endometrium in uterus without adenomyosis (0.153±0.018 and 0.178±0.026); compared with each other, the differences were statistically significant (all P<0.05). And the expressions of CXCL12 and CXCR4 proteins in uterine myometrium of adenomyosis were 0.222±0.045 and 0.126±0.058, respectively, which were higher than those in the control group (0.091±0.029 and 0.099±0.020); compared with each other, the differences were statistically significant (all P<0.05). (2) The expression levels of CXCL12 and CXCR4 mRNA in endometrium of patients with adenomyosis were 6.31±0.12 and 8.49±0.21, respectively, which were higher than those in the control group (1.23±0.10 and 1.36±0.13); compared with each other, the differences were statistically significant (all P<0.05). Moreover, the expression levels of CXCL12 and CXCR4 mRNA in myometrium of patients with adenomyosis were 9.11±0.12 and 8.45±0.16, respectively, which were higher than those in the control group (1.18±0.08 and 1.46±0.13); compared with each other, the differences were statistically significant (all P<0.05). (3) In endometrium and myometrium of uterus with adenomyosis, CXCL12 and CXCR4 mRNA expression levels were positively associated ( r=0.478, 0.542, all P<0.05). Conclusions:The levels of CXCL12 and CXCR4 in the endometrium and myometrium of adenomyosis are increased and positively correlated. The two chemokine may be involved in the development of adenomyosis.

As a transport channel for amino acids, solute carrier (SLC) exists in all kinds of cells, and its function is to transport various amino acids and provide necessary nutrients for the growth and development of cells. In recent years, SLC7A5 and SLC7A11 genes of SLC7 family members have been found to be highly expressed in various malignant tumors, which can promote the occurrence and development of tumors by providing necessary amino acids for tumors. Studies have shown that these genes are associated with a variety of malignant tumors, and their expression is closely related to the growth, metastasis, treatment and prognosis of tumor cells. Moreover, the results of multiple studies suggest that SLC7A5 and SLC7A11 genes can be used as therapeutic targets for malignant tumors. Clarifying the expression and clinical significance of the above genes in malignant tumors, the molecular biological mechanism and the progress of molecular targeted therapy are helpful to provide a new way for the diagnosis and treatment of malignant tumors.

In recent years, with the continuous development of biotechnology, liquid biopsy techno-logy has gradually become a research hotspot in the field of tumor research. As a non-invasive diagnostic method, liquid biopsy has great advantages compared with traditional methods. The liquid biopsy technology is precise, convenient, non-invasive and safe, and has an increasingly important clinical significance in the early diagnosis, treatment and prognosis assessment of esophageal squamous cell carcinoma.

OBJECTIVES: Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms. METHODS: This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting. RESULTS: Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax). CONCLUSIONS The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.
Humans ; Nasopharyngeal Carcinoma ; Paclitaxel/therapeutic use* ; Nasopharyngeal Neoplasms/metabolism* ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Cell Proliferation ; Cell Line, Tumor

Objective:To investigate the influencing factors for splenomegaly secondary to acute pancreatitis (AP) and construction of a nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 180 patients with AP who were admitted to Xuanwu Hospital of Capital Medical University from December 2017 to December 2021 were collected. There were 124 males and 56 females, aged (49±15) years. Among them, 60 AP patients who developed secondary splenomegaly were taken as the case group, including 48 males and 12 females, aged (47±13)years, and the rest of 120 cases of AP without secondary splenomegaly were taken as the control group, including 76 males and 44 females, aged (50±16)years. Observation indicators: (1) occurrence and clinical characteristics of splenomegaly secondary to AP; (2) influencing factors for splenomegaly secondary to AP; (3) construction and evaluation of a nomogram prediction model for splenomegaly secondary to AP. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the rank sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. The univariate analysis was performed using statistical methods appropriate to the data type. The optimal cut-off value was determined by the receiver operating characteristic curves. Multivariate analysis was conducted using the Logistic regression model with forward method. Based on the results of the multivariate analysis, a nomogram prediction model was constructed. The receiver operating characteristic curve was drawn, and the discrimination was evaluated using the area under curve. The consistency of the nomogram prediction model was evaluated using calibration curve, and its clinical benefit was evaluated using decision curve. Results:(1) Occurrence and clinical characteristics of splenomegaly secondary to AP. The first detection time of 60 patients with splenomegaly secondary to AP was 60(30,120)days after the onset of AP. Cases with persistent respiratory dysfunction, multiple organ failure, severity of illness as mild or moderately severe/severe, pancreatic and/or peripancreatic infection, surgery were 19, 17, 4, 56, 37, 32 for 60 patients with splenomegaly secondary to AP, versus 16, 19, 43, 77, 39, 29 for 120 patients without splenomegaly secondary to AP, respectively, showing significant differences in the above indicators between the two groups ( χ2=8.58, 3.91, 17.64, 13.95, 15.19, P<0.05). (2) Influencing factors for splenomegaly secondary to AP. Resuts of multivariate analysis showed that white blood cell count <5.775×10?/L within 24 hours of AP onset, revised computed tomography (CT) severity index >7 in 3-7 days after onset and the presence of local complications were independent risk factors influencing the splenomegaly secondary to AP ( odds ratio=3.85, 2.86, 6.40, 95% confidence interval as 1.68-8.85, 1.18-6.95, 1.56-26.35, P<0.05). (4) Construction and evaluation of a nomogram prediction model for splenomegaly secondary to AP. The nomogram prediction model was constructed based on white blood cell count within 24 hours of AP onset, revised CT severity index in 3-7 days after onset and local complications. The area under the receiver operating characteristic curve of the nomogram prediction model was 0.76 (95% confidence interval as 0.69-0.83, P<0.05), with a sensitivity of 0.87 and a specificity of 0.55. The calibration curve demonstrated consistency between the predicted rate from the nomogram prediction model and the actually observed rate. The decision curve analysis indicated that the nomogram prediction model had favorable clinical practicability. Conclusions:Patients with AP who develop secondary splenomegaly tend to have a higher severity of illness than those develop no secondary splenomegaly. White blood cell count <5.775×10?/L within 24 hours of AP onset, revised CT severity index >7 in 3-7 days after onset and presence of local complications are independent risk factors influencing splenomegaly secondary to AP, and its nomogram prediction model can predict incidence rate of splenomegaly secondary to AP.

Acute pancreatitis is one of the common acute abdominal conditions in the digestive system,and its incidence is on the rise.Although approximately 80％of cases involve mild patients without local complications,some patients develop local complications in the later stages of the disease,such as pancreatic pseudocysts and walled-off necrosis.Among these,infected pancreatic necrosis(IPN)is the most severe,with a mortality rate of up to 30％.In recent years,treatment approaches centered around minimally invasive surgery have achieved promising results;several recent clinical trials have also provided substantial new insights into the surgical diagnosis and treatment of IPN.However,it is worth noting that IPN exhibits considerable individual variability and complex treatment processes.Therefore,it is necessary to discuss surgical treatment strategies for IPN to offer clinical practitioners a reference for relevant management.