Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application.

Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

[Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway].

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

Comparison of two surgical strategies for fractures of the anterior process of the calcaneus with or without bridging plate fixation.

OBJECTIVE: To evaluate the therapeutic effects of applying internal fixation with a T-shaped locking plate that was used on the distal radius in fractures of the anterior process of the calcaneus (APC) with calcaneocuboid (CC) joint injury. METHODS: This retrospective study enrolled adult patients diagnosed with APC with CC joint injury that had received internal fixation with a T-shaped locking plate of the distal radius. Group NA underwent open reduction with 'not-across' CC joint plate fixation; and group A underwent open reduction with 'across' CC joint locking plate fixation. The outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) score, a visual analogue scale (VAS) pain score and radiological evaluations. RESULTS: A total of 72 patients were enrolled in the study; 36 in each group. At 1 month after surgery, the outcomes of group NA were superior to group A in terms of AOFAS and VAS scores. Compared with group A, group NA showed significantly lower intraoperative blood loss, operation time and length of hospital stay. There were no significant differences in the postoperative improvement of Bolher's and Gissane's angles between the two groups. CONCLUSION: Early functional recovery was faster in group NA than group A.

Saikosaponin D Inducing Apoptosis and Autophagy through the Activation of Endoplasmic Reticulum Stress in Glioblastoma.

Saikosaponin D (SSD), a saponin derivative, is extracted from Bupleurum falcatum. It exhibits an inhibitory effect on a number of tumor cells and is relatively safe when used at therapeutic doses. However, its effects on glioblastoma multiforme (GBM) have not been fully explored. This study is aimed at investigating the cytotoxic effects of SSD in GBM cell lines. SSD induces apoptosis and autophagy by activating endoplasmic reticulum (ER) stress in GBM cells. GBM cell proliferation activity and morphology were observed using the Cell Counting Kit-8 assay and hematoxylin and eosin staining. Hoechst 33258 fluorescence staining and flow cytometry were performed to assess apoptosis. Western blotting and immunocytochemical staining were used to detect protein expression and distribution. SSD significantly inhibited the proliferation of RG-2, U87-MG, and U251 cells in a dose-dependent manner, and the proportion of apoptotic cells increased significantly. Additionally, the expressions of ER-, apoptosis-, and autophagy-related proteins were significantly upregulated and distributed in the cytoplasm and nucleus. Therefore, SSD may be considered a novel treatment option for GBM. This study demonstrated the anti-GBM effect of SSD from the perspectives of cell apoptosis and autophagy.

Comparison of Efficacy of Percutaneous Vertebroplasty versus Percutaneous Kyphoplasty in the Treatment of Osteoporotic Vertebral Asymmetric Compression Fracture.

BACKGROUND: This study aims to compare the clinical efficacy of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral asymmetric compression fracture (OVACF). METHODS: This study retrospectively reviewed the patients who were diagnosed with OVACF between September 2015 and July 2019. Forty-one patients received PVP surgery (group A), and 44 patients received PKP surgery (group B). The visual analog scale, Oswestry Disability Index, scoliosis angle (SA), height of long side, height of short side (HS), and lateral height difference (LHD) before operation and 3 days and 1 year after operation were compared between both groups. The operation time, fluoroscopic time, hospital stay, cement volume, and complications were also compared between both groups. RESULTS: The visual analog scale and Oswestry Disability Index differed significantly between the groups 1 year after operation (P < 0.05). Compared with the preoperative results, there were significant differences in SA, height of long side, HS, and LHD 3 days and 1 year after operation (P < 0.05). Compared with group A, group B showed significantly better in SA, HS, and LHD in group B 3 days and 1 year after operation (P < 0.05). More patients in group A suffered cement leakage and scoliosis than group B after operation (P < 0.05). CONCLUSIONS: In our study, PVP and PKP are both effective in the treatment of OVACF, but PKP surgery had better long-term clinical efficacy.

[Clinical study of hydraulic perfusion pump and traditional water flushing for percutaneous endoscopic lumbar discectomy].

OBJECTIVE: To compare the clinical outcomes of hydraulic perfusion pump and traditional water fhushing in percutaneous endoscopic lumbar discectomy. METHODS: From January 2016 to December 2018, 72 patients with lumbar disc herniation failed to conservative treatment were enrolled in this study. The patients were divided into hydraulic perfusion pump group and traditional water flushing group, 36 cases in each group. There were no significant differences in gender, age, prominent segment, clinical classification, preoperative visual analogue scale (VAS) and Japanese Orthopaedic Association(JOA) score between two groups (P>0.05). All operations were performed by the same surgeon, and the operations were completed by hydraulic perfusion pumpflushing or traditional water flushing assisted surgery. The operation time, intraoperative blood loss, hospital stay were recorded;VAS and JOA scores were observed before and after operation;the incidences of postoperative complications were compared between two groups. RESULTS: All the patients were followed up for 12 to 24 (15.7±5.1) months. Compared with the traditional water flushing group, the operation time of the hydraulic perfusion pump group was shorter [(65.5±21.3) min vs (74.8±19.9) min, t=9.465, P=0.003], and intraoperative blood loss was less [(21.2±12.9)ml vs (27.4± 14.1) ml, t=8.331, P=0.012], there was no statistical difference in hospital stay between two groups. Postoperative VAS scores at 1 day, 2 weeks and the final follow-up and postoperative JOA scores at the final follow-up of the two groups of patients improved compared with those before operation, but there was no significant difference between two groups (P>0.05). In the traditional water flushing group, the intracranial hypertensionoccurred during operation and the operation time was forced to shorten in 5 cases, the nerve root adventitia injury in 4 cases, and the postoperative recurrence in 4 cases. No intracranial hypertension during operation was found in the hydraulic perfusion pump group, nerve root adventitia injury occurred in 1 case, postoperative recurrence in 2 cases. The incidence of complication of the hydraulic perfusion pump group was lower than that ofthe traditional water flushing group. CONCLUSION: Both hydraulic perfusion pump and traditional water flushing assisted percutaneous endoscopic lumbar disc herniation can achieve satisfactory clinical results, but the former has shorter operation time, clearer intraoperative vision, less bleeding, and fewer intraoperative and postoperative complications.

[Risk factors of non-surgical vertebral fracture after percutaneous kyphoplasty of single segment thoracolumbar fracture].

OBJECTIVE: To investigate the risk factors of non-surgical vertebral fracture after percutaneous kyphoplasty (PKP) in patients with single segment thoracolumbar osteoporotic vertebral compression fracture(OVCF). METHODS: The clinical data of 219 patients with single segment thoracolumbar osteoporotic vertebral compression fracture underwent percutaneous kyphoplasty from January 2010 to December 2015 were retrospectively analyzed. There were 29 cases in non-surgical vertebral body fracture group with 7 males and 22 females aged (67.35±9.92) years. Bone mineral density was(-3.89±0.72)SD, fracture compressed degree was (0.57±0.35)%, bone cement injected volume was (4.53±1.64) ml, and vertebral height recovery was (0.49±0.86)% on average. Ten cases were with vertebral body space fracture, 7 cases with bone cement leakage to the intervertebral disc, 9 cases with bone cement leakage to the peripheral tissue and 14 cases were treated by systemic anti-osteoporosis treatment after operation. Other 190 cases in non-surgical vertebral body without fracture group, and there were 42 males and 148 females, aged (66.98±7.55) years. Bone mineral density was (-3.13±0.59) SD, fracture compressed degree was (0.39±0.60)%, bone cement injected volume was (4.72±1.28) ml, and vertebral height recovery was (0.46±0.94)% on average. Among them, 13 cases were with vertebral body space fracture, 5 cases with bone cement leakage to the intervertebral disc, 29 cases with bone cement leakage to the peripheral tissue and 129 cases were treated by systemic anti-osteoporosis treatment after operation. The factors of gender, age, fracture compressed degree, fractured type, bone mineral density, bone cement injected volume, bone cement leakage, vertebral height recovery, adjacent vertebral fractures, and systemic anti-osteoporosis treatment were studied in the two groups for single factor analysis. For the results with significant differences among above factors, the multivariate logistic regression analysis was used to research the non-surgical vertebral fracture risk factors. RESULTS: Among the 219 patients with single thoracolumbar fractures, 29 cases occurred non-surgical vertebral fractures. The single factor analysis results showed that there was no significant correlation between non-surgical vertebral fracture occurrecne with age, sex, fracture compressed degree, bone cement injected volume, and vertebral height recovery(P>0.05), but there was a significant correlation between non-surgical vertebral fracture occurrence with fractured type, bone cement leakage, systemic anti-osteoporosis treatment, and bone mineral density (P<0.05). Multivariate logistic regression analysis showed that fractured type(OR=0.135), whether systemic anti-osteoporosis treatment (OR=3.793), bone cement leakage (OR=8.975), and bone density (OR=57.079) are risk factors for postoperative non-surgical vertebral fractures. CONCLUSIONS: Improving the quality of the people, systemic preventing and treating the osteoporosis, improving the surgical skills and decreasing the bone cement leakage during operation are effective methods to prevent postoperative non-surgical vertebral fractures.