Objective:To investigate whether neoadjuvant therapy can improve the prognosis of patients with pancreatic cancer.Methods:A retrospective case-control study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database on 12, 103 patients who underwent surgical treatment between January 1, 2010, and December 31, 2021. Patients were divided into the neoadjuvant therapy group ( n=3 276) and the upfront surgery group ( n=8 827) based on whether they received neoadjuvant treatment. The neoadjuvant therapy group included 2 342 patients receiving neoadjuvant chemotherapy and 934 patients receiving neoadjuvant chemoradiotherapy. The upfront surgery group consisted of 4 335 patients receiving adjuvant chemotherapy, 1 987 patients receiving adjuvant chemoradiotherapy, 63 patients receiving adjuvant radiotherapy, and 2 442 patients undergoing surgery alone. Propensity score matching was used to eliminate group differences and create a cohort with no statistical differences in other clinicopathological features except for the grouping variable. Variables such as age, gender, tumor location, race, population of residence, tumor diameter, household income, TNM stage, and information on radiotherapy and chemotherapy were used for 1∶1 case matching. T stage, N stage, and the use of radiotherapy or chemotherapy were matched exactly. After matching, 1 182 patients were included in each group: the neoadjuvant therapy group contained 1 155 patients receiving neoadjuvant chemoradiotherapy and 27 receiving neoadjuvant chemotherapy, while the upfront surgery group comprised 848 patients receiving adjuvant chemotherapy and 334 receiving adjuvant chemoradiotherapy. TNM staging was reported according to the 7th edition of the AJCC guidelines. The primary outcome was overall survival. Measurement data with skewed distributions were expressed as M( Q1, Q3), and intergroup comparisons were conducted using the Wilcoxon rank-sum test. Categorical data were compared using the chi-square test or the Fisher′s exact test. The Log-rank test and subgroup analyses to assess interactions between neoadjuvant therapy and subgroup in COX regression models were used to compare survival benefits across variables. Landmark analysis was performed to create segmented survival curves, studying the impact of neoadjuvant therapy on prognosis during different follow-up periods. Results:The neoadjuvant therapy group had a higher proportion of T 4 tumor involving celiac axis, superior mesenteric artery, and/or common hepatic artery compared to the upfront surgery group (14.7% vs 2.8%, P<0.001). Additionally, significant differences were observed between groups in terms of race, location, population of residence, age, tumor diameter, tumor stage, and adjuvant therapy regimen ( P<0.05). The median overall survival time in the neoadjuvant therapy group was 30 months, compared to 22 months in the upfront surgery group ( P<0.001). In the neoadjuvant therapy group, the median survival was 30 months for both neoadjuvant chemotherapy and chemoradiotherapy patients; in the upfront surgery group, it was 26 months for both adjuvant chemotherapy and chemoradiotherapy patients, 17 months for adjuvant radiotherapy patients, and 12 months for surgery-only patients. After propensity score matching, there were no differences in the distribution of clinical characteristics between groups ( P>0.05), and all patients in the matched cohort had received chemotherapy. The matched neoadjuvant therapy group had a longer median overall survival compared to the upfront surgery group (30 months vs 27 months, P<0.001). Subgroup interaction analysis revealed that T stage had a significant interaction with neoadjuvant therapy, both before (T 4 stage: HR=0.382, 95% CI: 0.319-0.458; T 2-T 3 stages: HR=0.696, 95% CI: 0.656-0.738; T 1 stage: HR=1.199, 95% CI: 0.867-1.657; interaction P<0.001) and after matching (T 4 stage: HR=0.581, 95% CI: 0.414-0.814; T 2-T 3 stages: HR=0.827, 95% CI: 0.734-0.931; T 1 stage: HR=1.320, 95% CI: 0.716-2.433; interaction P=0.043). Subgroup interaction analysis indicated that T 1 patients did not benefit from neoadjuvant therapy; survival curves plotted for matched T 1 patients showed no difference in survival between the neoadjuvant therapy group and the upfront surgery group ( P=0.323). Conversely, non-T 1 (T 2-T 4) stage patients showed significant survival benefits in both unmatched and matched cohorts ( P<0.001). Landmark analysis showing that the survival benefits occurred mainly in the early postoperative period of up to 3 years ( P<0.001), but there was no difference in overall survival between the neoadjuvant therapy group and the upfront surgery group of >3 years ( P>0.05). Patients with Arterial invasion (T 4 stage compared to T 1-T 3 stages) showed a similarly significant interaction with the benefit of neoadjuvant therapy in both the pre-matching cohort (interaction P<0.001) and the post-matching cohort (interaction P=0.037). Patients with T 4 stage disease in the neoadjuvant therapy group had longer overall survival compared to the upfront surgery group (median overall survival in pre-matching cohort: 30 months vs 13 months, P<0.001; median overall survival in post-matching cohort: 28 months vs 18 months, P=0.001). Among T 4 stage patients in the post-matching cohort, neoadjuvant therapy provided significant survival benefits during the early postoperative period of up to 3 years ( P=0.001). However, there was no difference in overall survival between the neoadjuvant therapy group and the direct surgery group beyond 3 years( P=0.729). Conclusions:The prognosis in the neoadjuvant therapy group was better than in the upfront surgery group. Propensity score matching and subgroup interaction analysis showed that non-T 1 and T 4 stage patients benefited more from neoadjuvant therapy, with benefits mainly seen in the early postoperative period (≤3 years).

Objective To analyze the deep venous thrombosis(DVT)after plasma infusion in a patient with congenital dysfibrinogene-mia(CD),and explore the relationship between the CD and DVT.Methods The clinical data were collected and the pedigree was investigated(3 subjects of 2 generations in total).The relevant indexes of coagulation factors of the patient and her family members were detected.The genomic DNA of peripheral blood was extracted for PCR amplification.All the exons,flanking sequences,5'and 3'untranslated regions of FGA,FGB and FGG genes of fibrinogen(Fg)of the patient were analyzed by direct sequencing.The corre-sponding mutation site was subjected to sequence in the other members of this family.The PyMol software was used to construct the pro-tein model before and after gene mutation.Results The patient was admitted to hospital for hysteromyomectomy.DVT appeared in 3 days after surgery.The prothrombin time(PT),thrombin time(TT),Fg activity(Fg∶C)and Fg antigen(Fg∶Ag)of the patient was 14.9 s,33.3 s,0.94 g/L and 2.10 g/L,respectively.The above four indicators in her mother were 14.7 s,32.8 s,0.97 g/L and 2.35 g/L,respectively.Gene sequencing revealed that both the patient and her mother had a heterozygous missense mutation c.2185G＞A(p.Glu729Lys)in exon 6 of the FGA gene.The protein model analysis demonstrated that p.Glu729Lys mutation changed the amino acid side chain and reduced the number of hydrogen bonds originally formed with Arg854.Conclusion A heterozygous missense mutation c.2185G＞A(NM_000508)in exon 6 of the FGA gene should be responsible for the low fibrinogen level in this pedigree,which might be the main reason for DVT after plasma infusion in this patient.

Objective:To preliminarily investigate the risk factors for distant metastasis and prognosis, and construct a prognostic nomogram in T 4 stage pancreatic cancer. Methods:A retrospective case-control study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) database for pancreatic patients from January 1, 2010, to December 31, 2021. Based on whether the tumor invaded the celiac axis, superior mesenteric artery, and/or common hepatic artery, 38 759 patients were divided into an arterial invasion group (T 4 stage, n=7 471) and a non-arterial invasion group (non-T 4 stage, n=31 288). Clinical and pathological data, including demographic characteristics, treatment information, and tumor data were collected. The primary outcome was overall survival. Categorical data were expressed as numbers (percentages), and intergroup comparisons were made using the chi-square test. Survival benefits were measured using the Log-Rank test. A multivariate logistic model was used to identify high-risk factors for metastasis in T 4 stage pancreatic cancer. Patients were randomly divided into training ( n=5 232) and validation ( n=2 239) sets at a 7∶3 ratio. A nomogram model was created based on independent prognostic factors from the multivariate Cox regression analysis, and the model′s predictive ability was evaluated using the C-index and calibration curves. Results:The overall metastasis rate in the arterial invasion group was higher than that in the non-arterial invasion group (32.8% vs 29.0%, P<0.001), with fewer patients showing no metastasis or single-organ metastasis (86.3% vs 89.7%, P<0.001) and higher rates of lung metastasis ( P<0.001), distant lymph node metastasis ( P<0.001), and other metastases excluding liver, lung, brain, bone, and distant lymph node metastases ( P<0.001). However, no significant difference was found between groups for liver, brain, or bone metastasis rates ( P>0.05). Surgical rates for T 4 stage patients were significantly lower than for non-T 4 stage patients (all patients: 10.7% vs 38.4%, P<0.001; M 0 stage patients: 15.0% vs 52.4%, P<0.001; M 1 stage patients: 2.1% vs 4.1%, P<0.001). Additionally, significant differences were observed in age, race, radiotherapy, chemotherapy, tumor location, tumor size, and tumor stage ( P<0.05). The median survival for patients with arterial invasion was 8 months, significantly lower than the 10-month median survival for non-arterial invasion patients ( P<0.001). The median survival for surgical patients with arterial invasion was 22 months, lower than the 24-month median for non-T 4 stage patients underwent surgery ( P<0.001) but significantly higher than for patients without surgery (T 4 stage patients without surgery: 8 months, P<0.001; non-T 4 stage patients without surgery: 6 months, P<0.001). For lymph node metastasis, patients with or without positive local lymph node metastasis had similar overall survival ( P>0.05). However, Patients with distant lymph node metastasis had significantly lower overall survival than that in patients without distant lymph node metastasis ( P<0.001). The multivariate logistic model indicated that tumor location in the body and tail ( OR=2.591, 95% CI: 2.343-2.867), positive regional lymph nodes ( OR=2.033, 95% CI: 1.836-2.252), and age <70 years old ( OR=1.183, 95% CI: 1.067-1.312) were risk factors for distant metastasis in arterial invasion patients. The multivariate Cox model showed that surgery ( HR=0.451, 95% CI: 0.405-0.503), radiotherapy ( HR=0.729, 95% CI: 0.677-0.784), chemotherapy ( HR=0.277, 95% CI: 0.258-0.297), tumor location in the body and tail ( HR=0.928, 95% CI: 0.874-0.985), and household income ≥$80, 000 ( HR=0.908, 95% CI: 0.853-0.968) were independent protective factors for prognosis in arterial invasion patients. Living in areas with a population ≤1 million ( HR=1.109, 95% CI: 1.044-1.178), age ≥70 years old ( HR=1.220, 95% CI: 1.150-1.296), larger tumor size (>2 cm but ≤4 cm: HR=1.124, 95% CI: 0.954-1.323; >4 cm: HR=1.310, 95% CI: 1.114-1.541), and having a metastatic burden (lung metastasis: HR=1.049, 95% CI: 0.869-1.267; distant lymph node metastasis: HR=1.179, 95% CI: 0.910-1.527; bone metastasis: HR=1.419, 95% CI: 0.854-2.359; brain or other metastasis: HR=1.519, 95% CI: 1.350-1.709; liver metastasis: HR=1.737, 95% CI: 1.600-1.886; two types of metastasis: HR=1.913, 95% CI: 1.689-2.168; three or more types: HR=2.436, 95% CI: 1.947-3.048) were independent risk factors for prognosis. The nomogram based on these prognostic factors had a C-index of 0.749 in the training set and 0.745 in the validation set; calibration curves in both sets were near the 45° line. Conclusions:High metastasis rates and low surgery rates are characteristic of pancreatic cancer with arterial invasion. Investigating the risk factors for distant metastasis and developing a prognostic nomogram incorporating metastatic burden hold significant clinical value for T 4 stage pancreatic cancer.

Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.
Humans ; Pancreatic Neoplasms/therapy* ; Prognosis ; Pancreas/pathology* ; Genetic Predisposition to Disease ; Genomics

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Aggrecans/metabolism* ; Animals ; Cartilage, Articular/metabolism* ; Chondrocytes/pathology* ; Cytoskeletal Proteins/metabolism* ; Mice ; Muscle Proteins/metabolism* ; Osteoarthritis/pathology* ; Temporomandibular Joint/pathology*

Objective: To assess the effects of different nutritional support methods on postoperative recovery in patients with gastric cancer. Methods: 98 patients who received radical gastrectomy were divided into three groups: parenteral nutrition group (PN group) (n=36), early enteral nutrition group (EEN group) (n=33) and early oral feeding group (EON group) (n=29). Tolerance of enteral nutrition, postoperative recovery and economic indicators were compared. Results: The number of laparoscopic-assisted surgeries was 18, 17 and 25 in PN group, EEN group and EON group, respectively. There was no significant difference in sex, age and body mass index(BMI) among the three groups. Gastrointestinal function recovered slowly in 3 cases, including 2 cases in EEN group and 1 case in EON group. 1 case in EON group had abdominal hemorrhage. Median postoperative hospital stay in PN, EEN and EON group was 11.0, 11.0 and 8.0 days respectively, and significant reduction can be found in EON group(P<0.001). The complication rates were 30.5% (11 cases), 12.1% (4 cases), and 13.8% (4 cases), respectively, with no statistically significant difference(P=0.102). The median nutritional support costs for PN group, EEN group, and EON group were 4 543.3, 974.2, and 265.0 yuan, respectively. The median albumin consumption was 90.0, 40.0, and 0 g, respectively. The EON groups were significantly lower (P<0.001). The results of the laparoscopic assisted subgroup and the ones of whole group were consistent. Conclusion Compared with parenteral nutrition and early enteral nutrition, early oral feeding can reduce the amount of albumin consumption, decrease the cost of nutrition support and shorten the average hospital stay after surgey without increasing the incidence of complications.

Objective To assess the effects of different nutritional support methods on postoperative recovery in patients with gastric cancer. Methods 98 patients who received radical gastrectomy were divided into three groups: parenteral nutrition group (PN group) (n＝36), early enteral nutrition group (EEN group) (n＝33) and early oral feeding group (EON group) (n＝29). Tolerance of enteral nutrition, postoperative recovery and economic indicators were compared. Results The number of laparoscopic?assisted surgeries was 18, 17 and 25 in PN group, EEN group and EON group, respectively. There was no significant difference in sex, age and body mass index ( BMI) among the three groups. Gastrointestinal function recovered slowly in 3 cases, including 2 cases in EEN group and 1 case in EON group. 1 case in EON group had abdominal hemorrhage. Median postoperative hospital stay in PN,EEN and EON group was 11.0, 11.0 and 8.0 days respectively, and significant reduction can be found in EON group(P＜0.001). The complication rates were 30.5%(11 cases), 12.1%(4 cases), and 13.8%(4 cases), respectively, with no statistically significant difference ( P＝0.102). The median nutritional support costs for PN group, EEN group, and EON group were 4 543.3, 974.2, and 265.0 yuan, respectively. The median albumin consumption was 90.0, 40.0, and 0 g, respectively. The EON groups were significantly lower ( P＜0.001). The results of the laparoscopic assisted subgroup and the ones of whole group were consistent. Conclusion Compared with parenteral nutrition and early enteral nutrition, early oral feeding can reduce the amount of albumin consumption, decrease the cost of nutrition support and shorten the average hospital stay after surgey without increasing the incidence of complications.

Objective To assess the effects of different nutritional support methods on postoperative recovery in patients with gastric cancer. Methods 98 patients who received radical gastrectomy were divided into three groups: parenteral nutrition group (PN group) (n＝36), early enteral nutrition group (EEN group) (n＝33) and early oral feeding group (EON group) (n＝29). Tolerance of enteral nutrition, postoperative recovery and economic indicators were compared. Results The number of laparoscopic?assisted surgeries was 18, 17 and 25 in PN group, EEN group and EON group, respectively. There was no significant difference in sex, age and body mass index ( BMI) among the three groups. Gastrointestinal function recovered slowly in 3 cases, including 2 cases in EEN group and 1 case in EON group. 1 case in EON group had abdominal hemorrhage. Median postoperative hospital stay in PN,EEN and EON group was 11.0, 11.0 and 8.0 days respectively, and significant reduction can be found in EON group(P＜0.001). The complication rates were 30.5%(11 cases), 12.1%(4 cases), and 13.8%(4 cases), respectively, with no statistically significant difference ( P＝0.102). The median nutritional support costs for PN group, EEN group, and EON group were 4 543.3, 974.2, and 265.0 yuan, respectively. The median albumin consumption was 90.0, 40.0, and 0 g, respectively. The EON groups were significantly lower ( P＜0.001). The results of the laparoscopic assisted subgroup and the ones of whole group were consistent. Conclusion Compared with parenteral nutrition and early enteral nutrition, early oral feeding can reduce the amount of albumin consumption, decrease the cost of nutrition support and shorten the average hospital stay after surgey without increasing the incidence of complications.