Pancreatic cancer is one of the most malignant tumors with a 5-year survival rate of 13%. Difficulty in early diagnosis,high tumor heterogeneity,high rate of drug resistance,and lack of effective new drugs are the main reasons for the poor therapeutic effect. Traditional cell line models cannot simulate the tumor environment in vitro and cannot reflect the heterogeneity of pancreatic cancer,while animal models have a long culture process and cannot be used for high-throughput screening. Pancreatic cancer organoids can be continuously expanded and cultured in vitro,which can realistically reflect the heterogeneity of pancreatic cancer and allow high-throughput drug screening,making it an ideal tool for individualized precision diagnosis and treatment of pancreatic cancer. According to recent studies on the evaluation of clinical drug efficacy using pancreatic cancer organoids,the drug sensitivity of pancreatic cancer organoids is highly consistent with the clinical efficacy,demonstrating the feasibility of drug sensitivity of pancreatic cancer organoids in guiding clinical therapy,comfirming the ability to discover potential therapeutic drugs through high-throughput drug screening of pancreatic cancer organoids. At the same time,this review reveals the importance of pancreatic cancer organoids as a model of the pancreatic cancer microenvironment for the development of new drugs and tumor microenvironment research. and the role of pancreatic cancer organoids as a model that can reflect the specific microenvironment of pancreatic cancer for new drug discovery and microenvironmental evaluation. Pancreatic cancer organoids and organ-on-chips are powerful tools for precision companion therapy and new drug discovery.

Pancreatic cancer is one of the most malignant tumors with a 5-year survival rate of 13%. Difficulty in early diagnosis,high tumor heterogeneity,high rate of drug resistance,and lack of effective new drugs are the main reasons for the poor therapeutic effect. Traditional cell line models cannot simulate the tumor environment in vitro and cannot reflect the heterogeneity of pancreatic cancer,while animal models have a long culture process and cannot be used for high-throughput screening. Pancreatic cancer organoids can be continuously expanded and cultured in vitro,which can realistically reflect the heterogeneity of pancreatic cancer and allow high-throughput drug screening,making it an ideal tool for individualized precision diagnosis and treatment of pancreatic cancer. According to recent studies on the evaluation of clinical drug efficacy using pancreatic cancer organoids,the drug sensitivity of pancreatic cancer organoids is highly consistent with the clinical efficacy,demonstrating the feasibility of drug sensitivity of pancreatic cancer organoids in guiding clinical therapy,comfirming the ability to discover potential therapeutic drugs through high-throughput drug screening of pancreatic cancer organoids. At the same time,this review reveals the importance of pancreatic cancer organoids as a model of the pancreatic cancer microenvironment for the development of new drugs and tumor microenvironment research. and the role of pancreatic cancer organoids as a model that can reflect the specific microenvironment of pancreatic cancer for new drug discovery and microenvironmental evaluation. Pancreatic cancer organoids and organ-on-chips are powerful tools for precision companion therapy and new drug discovery.

Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.

Objective To summarize the application of double valve ring enlargement combined with mitral Chimney technique (Chimney Commando) in the secondary valve replacement and to analyze the efficacy in the near and medium term. Methods Patients who underwent the secondary aortic valve and mitral valve (double valve) replacement by Chimney Commando in Wuhan Asia Heart Hospital from 2019 to 2022 were included, and their clinical data were retrospectively collected to analyze the safety and feasibility of this procedure in secondary valve replacement of small aortic root patients. Results A total of 49 patients (44 females and 5 males) were included. The body surface area was 1.64±0.17 m2. The time from the first operation was 13.10±5.90 years. Except for 4 patients whose first operation was valvuloplasty, the remaining 45 patients were all patients after valve replacement, 41 patients of double valves replacement, including 39 patients with mechanical valve and 2 patients with biological valve. The majority of the aortic valves were St.Jude regent 19 mm or St.Jude regent 21 mm, accounting for 30.61% and 34.69%, respectively. The mitral valves were predominantly St.Jude 25 mm mechanical valves, making up 65.31%. All patients underwent Chimney Commando double valve ring enlargement, and the mean time of aortic occlusion was 154.00±45.40 min. The mean size of the aortic valve was 23.90±1.40 mm and that of the mitral valve was 28.20±1.20 mm, and the transvalvular pressure difference across the aortic valve was 20.16±5.76 mm Hg at 6 months postoperatively. There was one death during hospitalization due to multi-organ failure. The follow-up time ranged from 1 to 24 months with a median time of 8 months. Two patients were implanted with permanent pacemakers during the follow-up period and 1 patient died due to massive stroke and malignant arrhythmia. Conclusion Chimney Commando is safe and effective in patients with secondary double valve replacement, and the postoperative prosthetic valves have good hemodynamics, and can achieve good clinical results in the near and medium term.

Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.

Objective:To investigate the effects of anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata in repairing destructive wounds and rebuilding function of hands or feet.Methods:This study was a retrospective observational study. From January 2022 to March 2023, 16 patients with destructive wounds in hands or feet combined with extensor tendon defects who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 12 males and 4 females, aged 3 to 63 years. The wounds were located on the hands in 12 cases and on the feet in 4 cases. The number of defective extensor tendon ranged one to five, and the length of the defect ranged from 2.5 to 6.0 cm. The wound area was 11.0 cm×5.5 cm to 29.0 cm×9.5 cm after debridement. The wounds were repaired with anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata, and the flap area was 12.0 cm×6.5 cm to 30.0 cm×11.0 cm. The fascia lata was used to repair the extensor tendon defects, and the harvesting area of fascia lata was 8.0 cm×3.0 cm to 12.0 cm×8.0 cm. The wounds in flap donor areas in 15 patients were sutured directly, and the wound in flap donor area in 1 patient was covered with medium-thickness skin graft from lower abdomen. The survival of flaps and the wound healing in donor and recipient areas of flaps were observed within 1 week after operation. The number of patients who underwent thinning and plastic surgery or tenolysis was recorded during postoperative follow-up. At the last follow-up, the recovery of sensory function of the transplanted flaps on hands or feet was evaluated, the efficacy of flap repair was evaluated according to the comprehensive flap evaluation scale, and the function of hands was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association. The following two indexes were compared, including the measured total active motion of the injured fingers and the foot function assessed using Maryland foot function scale between before surgery and at the last follow-up.Results:Arterial crisis occurred in flaps in 2 patients after operation, and the flaps survived after timely exploration; the flaps in the rest patients survived well after operation. No obvious scar hyperplasia or ulceration was observed in donor and recipient areas of flaps after operation. All patients were followed up for 8 to 16 months, of which 6 patients underwent flap thinning and plastic surgery 6 to 7 months after operation, and 4 patients underwent tenolysis 3 to 6 months after operation. At the last follow-up, the recovery of sensory function of flaps reached S1 level in 5 cases and S2 level in 11 cases, and the two-point discrimination only had 1 point. The efficacy of flap repair scored 80 to 91, which were evaluated as excellent in 5 cases, good in 9 cases, and acceptable in 2 cases. The hand function was evaluated as excellent in 5 cases, good in 5 cases, and acceptable in 2 cases. The active extension function of the injured finger/toe was reconstructed successfully, and the total active motion of the injured finger was (225±22)° at the last follow-up, which was significantly higher than (117±20)° before surgery ( t=119.59, P<0.05); the foot function score was 86±7 at the last follow-up, which was significantly higher than 29±7 before surgery ( t=222.68, P<0.05), and the foot function was evaluated as excellent in 2 cases, good in 1 case, and acceptable in 1 case. Conclusions:The operation of harvesting the anterolateral femoral perforator flap pedicled with oblique branch of lateral circumflex femoral artery is relatively simple. After the wounds on hands or feet being repaired with the flaps, the appearance and function are good, with no obvious scar hyperplasia in donor and recipient areas of flaps. The fascia lata carried by the flap can repair the extensor tendon defect at the same time and improve the movement of the finger/toe.

Objective:To investigate the influence of bacterial outer membrane vesicles (OMVs) tumor vaccine on tumor cell proliferation and CD8 + T cell infiltration of mouse with pancreatic cancer. Methods:The experimental study was conducted. The ovalbumin (OVA) lentivirus vector plasmid pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro was used to construct the mouse pancreatic cancer Pan02-OVA cells. The ClyA-Catchers-OMVs (CC-OMVs) originated from Escherichia coli and labeled antigenic peptide SpyTag-OVA were used to construct the OMVs tumor vaccine. Mouse CD8 + T cells were stimulated by OMVs tumor vaccine, and the effects of OMVs tumor vaccine on inhibiting pancreatic cancer cells proliferation and stimulating CD8 + T cell infiltration were analy-zed by in vitro cell killing assay, including the OMVs tumor vaccine stimulated T cell group and the control T cell group, subcutaneous pancreatic cancer model, including the OMVs tumor vaccine group and the control group, and immunohistochemical staining. Observation indicators: (1) identification of mouse pancreatic cancer Pan02-OVA cells; (2) morphological observation of CC-OMVs; (3) inhibi-tion of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells; (4) inhibi-tion of mouse pancreatic cancer by OMVs tumor vaccine; (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages. Results:(1) Identification of mouse pancreatic cancer Pan02-OVA cells. Results of laser scanning confocal microscopy showed that the mNeongreen fluorescence was expressed in Pan02-OVA cells infected with the OVA lentivirus vector plasmid of pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro. Results of Flow cytometry showed that using the mouse pancreatic cancer Pan02 cells as references, the protein expression rate of Flag on the Pan02-OVA cells was 90.7%. (2) Morphological observation of CC-OMVs. Results of transmission electron microscopy analysis showed that the CC-OMVs were in spherical shape, with a diameter <50 nm. (3) Inhibition of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells. Results of cell proliferation toxicity test showed that the absorbance at 450 nm of mouse pancreatic cancer Pan02-OVA cells was 0.41±0.12 and 1.05±0.15 in the OMVs tumor vaccine-stimulated T cell group and the control T cell group, respectively, showing a significant difference between the two groups ( t=9.54, P<0.05). (4) Inhibition of mouse pancreatic cancer by OMVs tumor vaccine. The weight of subcutaneous tumor tissue in the back of mouse was (81±10)g and (153±17)g in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.26, P<0.05). (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Results of immuno-histochemical staining showed that the numbers of CD8 + T cells staining in the mouse back subcu-taneous tumor tissues was 28.7±3.5 and 9.3±1.5 in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.74, P<0.05). Conclusion:Bacterial OMVs tumor vaccine can inhibit proliferation of pancreatic cancer cells and increase the numbers of CD8 + T cells infiltrated in pancreatic cancer tissue of mouse.

Objective: To explore the value of edema ring around the ablation zone on FS-T2WI for early phase effect evaluation of radiofrequency ablation (RFA) for treatment of malignant hepatic tumors. Methods: Totally 18 patients with liver cancer and 4 with liver metastasis who underwent RFA therapy were enrolled. Plain MR images were obtained to observe the morphological features of the edema ring around the ablation zone on FS-T2WI on the third day after RFA. Plain and multiphase enhanced MRI were obtained after RFA to observe the effect, as well as tumor markers. The value of continuity of edema ring on FS-T2WI for evaluating the effect of RFA was assessed. Results: High-signal edema ring was seen around the ablation zone on FS-T2WI in all 22 cases. The edema rings were continuous in 19 cases, among them the thickness of the edema rings were uniform in 11 cases, while were uneven but with regular shape and clear boundary in the other 8 cases. No abnormal enhancement was detected on the following enhanced MRI after RFA, and the tumor markers were stable in above 19 cases, both suggesting completed ablation. The edema rings were discontinuous in 3 cases of liver cancer, with protruding slightly high signal nodule which enhanced on MRI 1 month after RFA, and the serum alpha-fetoprotein were elevated, suggesting that the ablation area did not completely cover the tumor area, and the ablations were not complete. Conclusion: The edema ring around the ablation zone on plain FS-T2WI early phase after RFA has certain value in assessing the effect of RF for malignant liver tumors, especially for short-term effect of RFA.

Objective: To explore the expression of PTK7 in pancreatic ductal adenocarcinoma and its clinical significance. Methods: The clinical and follow-up data of 85 patients with pancreatic ductal adenocarcinoma who underwent radical surgery at Tianjin Medical University Cancer Institute and Hospital from May 2011 to January 2016 were analyzed. The expression of PTK7 in 85 pancreatic cancer tissues and the corresponding para-cancer tissues was detected by immunohistochemistry, and the relationship between PTK7 expression level and the clinical pathological features and prognosis was analyzed. Results: Positive expression of PTK7 was observed mainly in the cytoplasm, presenting as brownish yellow granules. It was noted that expression of PTK7 in pancreatic ductal adenocarcinoma tissues and para-carcinoma tissues was 70.6% (60/85) and 52.9% (45/85), respectively, and the positive rate in pancreatic ductal adenocarcinoma tissues was significantly higher than that in para-carcinoma tissues; the difference was statistically significant (P<0.05). The abnormal expression of PTK7 was correlated with the tumor stage, lymph node metastasis, and the vascular tumor embolus (P<0.05). The survival analysis suggested that the survival time or recurrence-free time of patients with PTK7 high expression in pancreatic duct adenocarcinoma was significantly shorter than in those with low expression (P<0.05, respectively). ShRNA interference of PTK7 was successfully established in the cell stabilizing system, verified by MTT and clone formation. Results indicated that cell survival was significantly lower in the shRNA experimental group compared to the control group (P<0.05), the number of colonies formed was significantly smaller in the shRNA experimental group compared to the control group (P<0.05), and the expression of proliferation-related proteins Ki-67 and PCNA was significantly lower in the shRNA experimental group compared to the control group (P<0.05, respectively). Conclusions: The up-regulation of PTK7 expression in pancreatic ductal ad-enocarcinoma tissues was associated with the tumor stage, lymph node metastasis, and the vascular tumor thrombus, suggesting poor prognosis. It was also found that in pancreatic cancer cell lines, PTK7 could promote the proliferation of pancreatic cancer cells by regulating the levels of proliferative factors Ki-67 and PCNA.

The effect of the treatment of 112I particle therapy in solid tumor is remarkable and with less side effect.This study retrospectively analyzed the clinical data of 125I particles implantation combined systemic chemotherapy in the treatment of locally advanced pancreatic cancer patients.Main observation indexes included:the overall median survival,1 year survival rate,pain relief rate,the postoperative complications.Intraoperative 125I particles implantation combined with postoperative chemotherapy in treatment of locally advanced pancreatic cancer patient was safety,which can effectively prolong patient survival and relieve patients' pain.