Objective: To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Methods: Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3–28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6–95.3) and the DCR was 95.8% (95% CI=78.9–99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4–34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Conclusion Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative firstline treatment option for patients with R/M CC.

Objectives:To investigate the impact on lumbar spine biomechanical performance of endoscopic lumbar interbody fusion(Endo-LIF)via two approaches,namely endoscopic transforaminal lumbar interbody fu-sion(Endo-TLIF)and endoscopic posterior lumbar interbody fusion(Endo-PLIF)through finite element analysis.Methods:The L3-L5 CT scan data of a 24-year-old healthy male volunteer was collected to establish a three-dimensional finite element model containing conical bone,cancellous bone and posterior structure of L3-L5 vertebrae.The validity of the model was verified by comparing with other previous studies.The clini-cal and radiological data of 40 patients underwent Endo-LIF were analyzed retrospectively,and according to different operational approaches,the patients were divided into Endo-TLIF group(n=19)and Endo-PLIF group(n=21).The cage positions and angles of the patients were measured,and the facet joint preservation ratios were calculated to determine the cage placing positions and angles in constructing finite element surgical models.Finally,four finite element surgical models were constructed as Endo-TLIF+45° cage,Endo-TLIF+60° cage,Endo-PLIF+45° cage,and Endo-PLIF+60° cage.The range of motion(ROM)at the fusion segment and the maximum von Mises stress of endplates,cages,screws,rods,and bone-screw interfaces were calculated.Results:The ROMs of fusion segments in all surgical models reduced significantly compared with the intact model.The maximum von Mises stress of endplates in the surgical segment increased significantly under the flexion conditions in all surgical models.The maximum von Mises stress at the bone-screw interfaces of the Endo-PLIF model was significantly increased compared with the Endo-TLIF model under left and right rota-tion conditions(23％-84％).The maximum von Mises stress of the endplate and cage in the 60° cage models was higher than that in the 45° cage models.In the Endo-PLIF model,the stress of internal fixations and endplates was significantly increased compared with the Endo-TLIF model under left and right rotation condi-tions.Conclusions:Comparing with Endo-TLIF,Endo-PLIF has significantly higher maximum von Mises stress around the internal fixations,especially under rotational conditions,with greater risk of internal fixation failure.

OBJECTIVE: To investigate the molecular mechanism underlying the inhibitory effect of aloin on the proliferation and migration of gastric cancer cells. METHODS: Human gastric cancer MGC-803 cells treated with 100, 200 and 300 μg/mL aloin were examined for changes in cell viability, proliferation and migration abilities using CCK-8, EdU and Transwell assays. HMGB1 mRNA level in the cells was detected with RT-qPCR, and the protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 were determined using Western blotting. JASPAR database was used to predict the binding of STAT3 to HMGB1 promoter. In a BALB/c-Nu mouse model bearing subcutaneous MGC-803 cell xenograft, the effect of intraperitoneal injection of aloin (50 mg/kg) on tumor growth was observed. The protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 in the tumor tissue was examined using Western blotting, and tumor metastasis in the liver and lung tissues was detected using HE staining. RESULTS: Treatment with aloin concentration-dependently inhibited the viability of MGC-803 cells (P < 0.05), significantly reduced the number of EdU-positive cells (P < 0.01), and attenuated the migration ability of the cells (P < 0.01). Aloin treatment dose-dependently down-regulated HMGB1 mRNA expression (P < 0.01), lowered the protein expressions of HMGB1, cyclin B1, cyclin E1, MMP-2, MMP-9 and p-STAT3, and up-regulated E-cadherin expression in MGC-803 cells. Prediction based on JASPAR database suggested that STAT3 could bind to the promoter region of HMGB1. In the tumor-bearing mice, aloin treatment significantly reduced the tumor size and weight (P < 0.01), lowered the protein expressions of cyclin B1, cyclin E1, MMP-2, MMP-9, HMGB1 and p-STAT3 and increased the expression of E-cadherin in the tumor tissue (P < 0.01). CONCLUSION Aloin attenuates the proliferation and migration of gastric cancer cells by inhibiting the STAT3/HMGB1 signaling pathway.
Humans ; Animals ; Mice ; Stomach Neoplasms ; Cyclin B1 ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; HMGB1 Protein ; Signal Transduction ; Cell Proliferation ; STAT3 Transcription Factor

Traditional Chinese medicine (TCM) with a long history in China has demonstrated unique advantages in treating a variety of cardiovascular diseases, with promising prospects. We exemplify the TCM advantages with 3 major cardiovascular diseases: coronary heart disease, hypertension, and chronic heart failure. With both national and international guidelines, consensus, systematic reviews, and randomized controlled trials as evidence, we used the modified Jadad and AMSTAR-1 scales to evaluate the evidence quality and then systematically evaluated the clinical effects and benefits of TCM on cardiovascular diseases, aiming to provide fresh insights into the research methodologies and future development directions for TCM-dominant diseases.

【Objective】 To compare the perioperative blood loss between interlaminar and transforaminal approaches by percutaneous endoscopic discectomy in order to provide more reference for guiding the proper choice of surgical methods clinically. 【Methods】 We retrospectively analyzed the clinical data of 160 patients who underwent percutaneous endoscopic lumbar discectomy from June 2019 to November 2020， with 80 patients in interlaminar approach group and 80 in transforaminal approach group. The blood loss was calculated according to Gross formula. 【Results】 The perioperative total blood loss （mL）， hidden blood loss （mL） and hemoglobin loss （g/L） were significantly lower in interlaminar approach group than in transforaminal approach group （119.73±179.26 vs. 158.6±190.65， 109.73±179.53 vs. 148.78±190.19， 3.76±8.12 vs. 4.31±7.62） （P<0.05）. However， there was no significant difference in visible blood loss between the two groups. 【Conclusion】 The perioperative hidden blood loss accounts for a large proportion in percutaneous endoscopic lumbar discectomy. In addition， the interlaminar approach causes less blood loss than the transforaminal approach.

Objective:To discusses effectiveness of CTA in the classification of first plantar metatarsal artery and its application value in thumb reconstruction.Methods:Thirty-six cases who underwent thumb reconstruction with free second toe or hallucis flap between December, 2015 and December, 2018 were retrospectively analyzed. Among these cases, 22 cases were injured by machine stranding, 7 cases by heavy objects, and 7 cases were injured by rolling. Exact first plantar metatarsal arteries of all these cases were evaluated by using CTA preoperatively. And compared with intraoperative findings at the donor sites. Free first or second toe flap for thumb reconstruction were designed preoperatively based on branching pattern of first plantar metatarsal arteries.Results:The origin, course, 3-dimensional (3D) anatomical relationship with surrounding tissues and branching pattern of all these feet first plantar metatarsal arteries of 35 cases (70 feet)were well displayed in CTA images, and 1 case (2 feet) were showed poor vascular continuity and artifacts in CTA (2.78%). According to the branching pattern of first plantar metatarsal arteries, 29 cases (58 feet, 80.56%) were ramifying type, 5 cases (10 feet, 13.88%) were main trunk type, and 1 case (2 feet, 2.78%) were tiny branch type. Preoperative CTA images and intraoperative findings at the donor site of 35 cases were remarkably consistent. According to CTA images, 27 cases underwent thumb reconstruction with hallucis flap, 8 cases underwent thumb reconstruction with second toe, and 1 case of poor vascular continuity and artifacts in CTA underwent thumb reconstruction with hallucis flap eventually. All these cases were followed-up for 6-24 (average 12) months, and all reconstructed thumbs survived. The clinical outcomes of all these reconstructed thumbs were good with satisfactory appearance, sensory recovery, excellent motion. The donor feet of all cases recovered well.Conclusion:High-quality 3D images of first plantar metatarsal arteries could be obtained by CTA, allowing preoperative assessment of blood supply and planning of donor site. Therefore, success rate of reconstructed operation could be improved with low disability rate of donor site.

Objective:To investigate the clinical efficacy of hyperbaric oxygen(HBO) combined with vacuum sealing drainage (VSD) in the treatment of 46 patients with early osteofascial compartment syndrome (OCS), and to analyze the value of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) for prognostic prediction.Methods:A total of 46 patients with early OCS admitted to the Department of Orthopedics of Yantai Mountain Hospital from September 2015 to March 2020 were retrospectively analyzed. According to the treatment methods, they were divided into observation group ( n=46) and control group ( n=43). The control group was treated with VSD and conventional symptomatic treatment, while the observation group was treated with HBO on the basis of the treatments of the control group. The clinical efficacy was compared after 3 courses of treatment. The pain was graded before and after treatment by visual analogue scale (VAS); the time of swelling subsiding and length of hospital stay were respectively recorded; the freshness and infection of granulation tissue at the incision site of the affected limb were observed, and primary suture or secondary skin grafting was conducted based on evaluation; enzyme linked immunosorbent assay (ELISA) was applied to measure the levels of serum TNF-α and IL-6 at different time points for the prediction of the development of the disease. Results:After 3 courses of treatment, the effective rate of the observation group (97.8%) was significantly higher than that of the control group (81.4%) ( P<0.05). The secondary skin grafting rate in the observation group (53.5%) was significantly lower than that in the control group (21.7%), and the rate of granulation tissue without infection (80.4%) was significantly higher than that of the control group (51.2%) ( P<0.05). The time of swelling subsiding [(13.14 ±3.42)d] and length of hospital stay [(16.55±3.52)d] in the observation group were significantly lower than those in the control group [time of swelling subsiding: (22.39 ±4.48)d; length of hospital stay: (26.87±5.51)d] ( P<0.05). The VAS scores of the observation group were significantly lower than those of the control group on the 7th, 14th, and 21st days after operation ( P<0.05). The levels of serum TNF-α and IL-6 in the observation group were significantly lower than those in the control group on the 7th and 14th days after operation ( P<0.05), but no significant difference was observed on the 21st day ( P>0.05). Conclusion:HBO combined with VSD in the treatment of early OCS can improve the blood circulation of the affected limb, reduce the incidence of incision infection, promote wound healing, and reduce limb pain, so as to improve the curative effect.

Objective:To investigate the clinical efficacy of hyperbaric oxygen(HBO) combined with vacuum sealing drainage (VSD) in the treatment of 46 patients with early osteofascial compartment syndrome (OCS), and to analyze the value of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) for prognostic prediction.Methods:A total of 46 patients with early OCS admitted to the Department of Orthopedics of Yantai Mountain Hospital from September 2015 to March 2020 were retrospectively analyzed. According to the treatment methods, they were divided into observation group ( n=46) and control group ( n=43). The control group was treated with VSD and conventional symptomatic treatment, while the observation group was treated with HBO on the basis of the treatments of the control group. The clinical efficacy was compared after 3 courses of treatment. The pain was graded before and after treatment by visual analogue scale (VAS); the time of swelling subsiding and length of hospital stay were respectively recorded; the freshness and infection of granulation tissue at the incision site of the affected limb were observed, and primary suture or secondary skin grafting was conducted based on evaluation; enzyme linked immunosorbent assay (ELISA) was applied to measure the levels of serum TNF-α and IL-6 at different time points for the prediction of the development of the disease. Results:After 3 courses of treatment, the effective rate of the observation group (97.8%) was significantly higher than that of the control group (81.4%) ( P<0.05). The secondary skin grafting rate in the observation group (53.5%) was significantly lower than that in the control group (21.7%), and the rate of granulation tissue without infection (80.4%) was significantly higher than that of the control group (51.2%) ( P<0.05). The time of swelling subsiding [(13.14 ±3.42)d] and length of hospital stay [(16.55±3.52)d] in the observation group were significantly lower than those in the control group [time of swelling subsiding: (22.39 ±4.48)d; length of hospital stay: (26.87±5.51)d] ( P<0.05). The VAS scores of the observation group were significantly lower than those of the control group on the 7th, 14th, and 21st days after operation ( P<0.05). The levels of serum TNF-α and IL-6 in the observation group were significantly lower than those in the control group on the 7th and 14th days after operation ( P<0.05), but no significant difference was observed on the 21st day ( P>0.05). Conclusion:HBO combined with VSD in the treatment of early OCS can improve the blood circulation of the affected limb, reduce the incidence of incision infection, promote wound healing, and reduce limb pain, so as to improve the curative effect.

OBJECTIVE: To investigate the effect of calenduloside E on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cells and explore the underlying molecular mechanism. METHODS: CCK-8 assay was used to examine the effect of different concentrations of calenduloside E (0-30 μg/mL) on the viability of RAW264.7 cells. The release of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in RAW264.7 cells in response to pretreatment with 6, 8, and 10 μg/mL calenduloside E for 2 h followed by stimulation with 100 ng/mL LPS was detected using enzyme-linked immunosorbent assay (ELISA). The expression levels of iNOS and COX-2 and the activation of JAK-stats, MAPKs and NF-кB signaling pathways in the treated cells were determined using Western blotting. A reactive oxygen species (ROS) detection kit was used to detect ROS production in the cells, and the nuclear translocation of the transcription factor stat3 was observed by laser confocal microscopy. RESULTS: Calenduloside E below 20 μg/mL did not significantly affect the viability of RAW264.7 cells. Calenduloside E dose-dependently decreased the expression levels of iNOS and COX-2 induced by LPS, inhibited LPS-induced release of TNF-α and IL-1β, and suppressed LPS-induced JAK1-stat3 signaling pathway activation and stat3 nuclear translocation. Calenduloside E also significantly reduced ROS production induced by LPS in RAW264.7 cells. CONCLUSIONS Calenduloside E inhibits LPS-induced inflammatory response by blocking ROS-mediated activation of JAK1-stat3 signaling pathway in RAW264.7 cells.
Animals ; Lipopolysaccharides ; Mice ; NF-kappa B ; Oleanolic Acid ; analogs & derivatives ; RAW 264.7 Cells ; Reactive Oxygen Species ; Saponins ; Signal Transduction

Objective To investigate the target blood pressure level of restrictive fluid resuscitation in patients with traumatic hemorrhagic shock. Methods Sixty patients with traumatic hemorrhagic shock admitted to the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2018 were enrolled. All patients were resuscitated with sodium acetate ringer solution after admission. According to the difference of mean arterial pressure (MAP) target, the patients were divided into low MAP (60 mmHg ≤ MAP < 65 mmHg, 1 mmHg = 0.133 kPa), middle MAP (65 mmHg ≤ MAP < 70 mmHg) and high MAP (70 mmHg ≤ MAP < 75 mmHg) groups by random number table using the admission order with 20 patients in each group. Those who failed to reach the target MAP after 30-minute resuscitation were excluded and supplementary cases were deferred. The restrictive fluid resuscitation phase was divided into three phases: before fluid resuscitation, liquid resuscitation for 30 minutes and 60 minutes. The most suitable resuscitation blood pressure level was further speculated by monitoring the inflammatory markers and hemodynamics in different periods in each group of patients. Pearson correlation analysis was used to detect the correlation of variables. Results Before fluid resuscitation, there was no significant difference in hemodynamics or expressions of serum cytokines among the three groups. Three groups of patients were resuscitated for 30 minutes to achieve the target blood pressure level and maintain 30 minutes. With the prolongation of fluid resuscitation time, the central venous pressure (CVP), cardiac output (CO) and cardiac index (CI) were increased slowly in the three groups, and reached a steady state at about 30 minutes after resuscitation, especially in the high MAP group and the middle MAP group. The expressions of serum inflammatory factors in the three groups were gradually increased with the prolongation of fluid resuscitation time. Compared with the low MAP group and the high MAP group, after 30 minutes of resuscitation the middle MAP group was superior to the other two groups in inhibiting the expressions of pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and promoting anti-inflammatory factors IL-10 [TNF-α mRNA (2-ΔΔCt):0.21±0.13 vs. 0.69±0.34, 0.57±0.35; IL-6 mRNA (2-ΔΔCt): 0.35±0.31 vs. 0.72±0.39, 0.59±0.42; IL-10 mRNA (2-ΔΔCt): 1.25±0.81 vs. 0.61±0.46, 0.82±0.53; all P < 0.05], but there was no significant difference in promoting the expression of IL-4 mRNA among three groups. At 60 minutes of resuscitation, compared with the low MAP group and the high MAP group, the middle MAP group could significantly inhibit the expressions of TNF-α, IL-6 and promote IL-10 [TNF-α mRNA (2-ΔΔCt): 0.72±0.35 vs. 1.05±0.54, 1.03±0.49; IL-6 mRNA (2-ΔΔCt): 0.57±0.50 vs. 1.27±0.72, 1.01±0.64; IL-10 mRNA (2-ΔΔCt): 1.41±0.90 vs. 0.81±0.48, 0.94±0.61; all P < 0.05]. Compared with the high MAP group, the middle MAP group had significant differences in promoting the expression of IL-4 mRNA (2-ΔΔCt: 1.32±0.62 vs. 0.91±0.60, P < 0.05). There was no significant difference in serum cytokine expressions at different time points of resuscitation between the low MAP group and the high MAP group (all P > 0.05). Correlation analysis showed that there was a strong linear correlation between MAP and mRNA expressions of TNF-α, IL-6, IL-10 in the middle MAP group (r value was 0.766, 0.719, 0.692, respectively, all P < 0.01), but had no correlation with IL-4 (r = 0.361, P = 0.059). Fitting linear regression analysis showed an increase in 1 mmHg per MAP, the expression of TNF-α mRNA increased by 0.027 [95% confidence interval (95%CI) = 0.023-0.031, P < 0.001], IL-6 mRNA increased by 0.021 (95%CI = 0.017-0.024, P < 0.001), and IL-10 mRNA increased by 0.049 (95%CI = 0.041-0.058, P < 0.001). Conclusions When patients with traumatic hemorrhagic shock received restrict fluid resuscitation at MAP of 65-70 mmHg, the effect of reducing systemic inflammatory response and improving hemodynamics is better than the target MAP at 60-65 mmHg or 70-75 mmHg. It is suggested that 65-70 mmHg may be an ideal target MAP level for restrictive fluid resuscitation.