Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus.

BACKGROUND: Hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT) exhibit poor prognoses and treatment responses. AIM: To investigate efficacies and safety of the combination of PD-1 inhibitor, transcatheter arterial chemoembolization (TACE) and Lenvatinib in HCC subjects comorbid with PVTT. METHODS: From January 2019 to December 2020, HCC patients with PVTT types I-IV were retrospectively enrolled at Beijing Ditan Hospital. They were distributed to either the PTL or TACE/Lenvatinib (TL) group. The median progression-free survival (mPFS) was set as the primary endpoint, while parameters like median overall survival, objective response rate, disease control rate (DCR), and toxicity level served as secondary endpoints. RESULTS: Forty-one eligible patients were finally recruited for this study and divided into the PTL (n = 18) and TL (n = 23) groups. For a median follow-up of 21.8 months, the DCRs were 88.9% and 60.9% in the PTL and TL groups (P = 0.046), res-pectively. Moreover, mPFS indicated significant improvement (HR = 0.25; P < 0.001) in PTL-treated patients (5.4 months) compared to TL-treated (2.7 months) patients. There were no treatment-related deaths or differences in adverse events in either group. CONCLUSION: A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types I-IV.

Enhanced Bone Regeneration through Regulation of Mechanoresponsive FAK-ERK1/2 Signaling by ZINC40099027 during Distraction Osteogenesis.

Background: Focal adhesion kinase (FAK) is activated by mechanical stimulation and plays a vital role in distraction osteogenesis (DO), a well-established but lengthy procedure for repairing large bone defects. Both angiogenesis and osteogenesis contribute to bone regeneration during DO. However, the effects of ZINC40099027 (ZN27), a potent FAK activator, on angiogenesis, osteogenesis, and bone regeneration in DO remain unknown. Methods: The angiogenic potential of human umbilical vein endothelial cells (HUVECs) was evaluated using transwell migration and tube formation assays. The osteogenic activity of bone marrow mesenchymal stem cells (BMSCs) was assessed using alkaline phosphatase (ALP) and alizarin red s (ARS) staining. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence staining were used to assay angiogenic markers, osteogenic markers, and FAK-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In vivo, a rat tibia DO model was established to verify the effects of ZN27 on neovascularization and bone regeneration using radiological and histological analyses. Results: ZN27 promoted the migration and angiogenesis of HUVECs. Additionally, ZN27 facilitated the osteogenic differentiation of BMSCs, as revealed by increased ALP activity, calcium deposition, and expression of osteogenesis-specific markers. The ERK1/2-specific inhibitor PD98059 significantly hindered the effects of ZN27, suggesting the participation of FAK-ERK1/2 signaling in ZN27-enhanced angiogenesis and osteogenesis. As indicated by improved radiological and histological features, ZN27 induced active angiogenesis within the distraction area and accelerated bone regeneration in a rat DO model. Conclusion: Our results show that ZN27 targets FAK-ERK1/2 signaling to stimulate both angiogenesis and osteogenesis, and ZN27 accelerates bone regeneration in DO, suggesting the therapeutic potential of ZN27 for repairing large bone defects in the mechanobiological environment during DO.

Sound reduces saccadic chronostasis illusion.

The saccadic chronostasis illusion refers to the duration overestimation of the first visual stimulation after saccadic eye movement, which is also known as "stopped clock illusion." The present study investigated whether saccadic chronostasis would be observed in the auditory modality and whether the saccade-induced time dilation in the visual modality would be reduced by a synchronously presented sound. In each trial, a unisensory visual stimulus, unisensory sound, or bimodal audio-visual stimulus with a duration of 200-800 ms (probe stimulus) was presented at the saccade target location and temporally around the offset of the saccade, followed by a unisensory visual or auditory standard stimulus for a fixed 500 ms. Participants were required to identify which of the two stimuli (probe or standard) presented in the target modality (visual or auditory) was perceived as longer. The results showed that no saccadic chronostasis was observed in the auditory modality, regardless of whether the sound was presented alone or synchronously accompanied by a visual stimulus. Interestingly, the magnitude of the saccadic chronostasis illusion was reduced by the synchronously presented sound. Moreover, the combined effect of the saccade and sound on visual time perception fits well with the standard scalar model, and the weight of the cross-modal effect was higher than that of saccadic visual time dilation. These results suggest that sound dominates vision in time processing during saccades and linearly modulates saccadic chronostasis, which follows the Scalar Expectancy Theory.

Comparison of detection methods for carbonation depth of concrete.

This paper presents comprehensive research of the advantages and applicability of various concrete carbonation detection methods. Employing a combination of Phenolphthalein indicator (PI), Thermogravimetric analysis (TGA), X-ray phase analysis (XRD), Fourier transform infrared spectroscopy (FTIR), and Quantitative calcium carbonate analysis (CA), a detailed comparison to determine the carbonation depth in the partial carbonation zone of concrete specimens is conducted. Among the quantitative analysis methods, CA measures CaCO3 content based on chemical reactions, while TGA obtains the concentration distribution of Ca(OH)2 and CaCO3. Among qualitative analysis methods, XRD tested the intensity distribution of Ca(OH)2 and CaCO3, while FTIR traced the characteristic peaks of C-O functional groups in a specific spectral range to determine the depth of carbonation of concrete. Results indicate that the depth of carbonation values measured by CA, TGA, XRDA, and FTIR are 2-3 times higher than those measured by PI. This research may provide valuable insights for the design of carbonation detection in concrete.

Serological Responses after a Fourth Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis.

The humoral immune response and safety of the fourth dose of the coronavirus disease 2019 (COVID-19) vaccine in solid organ transplant (SOT) recipients need to be fully elucidated. We conducted a systematic review and meta-analysis to assess the efficacy and safety associated with this additional dose of the COVID-19 vaccine in the SOT recipients. A comprehensive search was conducted to identify studies on SOT patients without prior natural SARS-CoV-2 infection who received the fourth dose of the COVID-19 vaccine. Serological antibody responses following vaccination were synthesized by a meta-analysis of proportions. The proportions for each outcome were integrated by using a random-effects model. Approximately 56-92% of the SOT patients developed a humoral immune response, and the pooled seroprevalence rate was 75% (95% confidence interval [CI], 62-82%) after administering the third vaccine dose. Following the fourth dose of vaccination, approximately 76-95% of the patients developed a humoral immune response. The pooled seroprevalence rate after the fourth dose was 85% (95% CI, 79-91%). Of the patients who initially tested seronegative after the second dose, approximately 22-76% of patients subsequently became seropositive after the third dose. The pooled seroconversion rate for the third dose was 47% (95% CI, 31-64%). Among the patients who were seronegative after the third dose, approximately 25-76% turned seropositive after the fourth dose. The pooled seroconversion rate after the fourth dose was 51% (95% CI, 40-63%). Safety data were reported in three studies, demonstrating that adverse effects following the fourth dose were generally mild, and patients with these adverse effects did not require hospitalization. No transplant rejection or serious adverse events were observed. A fourth dose of the COVID-19 vaccine in SOT recipients was associated with an improved humoral immune response, and the vaccine was considered relatively safe.

A multicenter prospective study of TACE combined with lenvatinib and camrelizumab for hepatocellular carcinoma with portal vein tumor thrombus.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) predicts a poor prognosis. The aim of the present study was to evaluate the efficacy and safety of using lenvatinib and camrelizumab combined with transarterial chemoembolization (TACE) to treat HCC with PVTT. METHODS: This was a single-arm, open-label, multicenter, and prospective study. Eligible patients with advanced HCC accompanied by PVTT were enrolled to receive TACE combined with lenvatinib and camrelizumab. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: Between April 2020 and April 2022, 69 patients were successfully enrolled. With a median follow-up time of 17.3 months, the median age of the patient cohort was 57 years (range: 49-64 years). According to modified Response Evaluation Criteria in Solid Tumors, the ORR was 26.1% (18 partial responses [PRs]) and the DCR was 78.3% (18 PRs, 36 stable diseases [SDs]). The median PFS (mPFS) and median OS (mOS) were 9.3 and 18.2 months, respectively. And tumor number >3 was identified as an adverse risk factor for both PFS and OS. The most common adverse events across all grades included fatigue (50.7%), hypertension (46.4%), and diarrhea (43.5%). Twenty-four patients (34.8%) experienced Grade 3 toxicity that was relieved by dose adjustment and symptomatic treatment. No treatment-related deaths occurred. CONCLUSIONS: TACE combined with lenvatinib and camrelizumab is a well-tolerated modality treatment with promising efficacy for advanced HCC with PVTT.

Comparison of the clinical efficacy of three internal fixation methods in the treatment of Edinburgh type IB fractures of the proximal clavicle.

Clavicle fractures are one of the most common fractures and usually occur in the medial third of the clavicle. The study explored the efficacy of three internal fixation methods to treat Edinburgh IB fractures of the proximal clavicle. 68 patients with Edinburgh IB fractures of the proximal clavicle were divided into T-shaped plate group, double-miniature steel plate group and memory alloy embracing device group. Postoperative complications, return time to work, and fracture healing time were recorded. The clinical efficacy was evaluated by Constant-Murley score of shoulder joint, Visual Analogue Scale (VAS) score of pain, and arm-shoulder-hand dysfunction score. The operative time of the memory alloy embracing device group was significantly better than T-shaped plate group and double-miniature steel plate group. The length of surgical incision in the double-miniature steel plate group was significantly shorter than that in the T-shaped plate group and the memory alloy embracing device group. The hospitalization cost and recovery time of the double-plate and memory alloy hug groups were lower than those of the T-plate group. The double-miniature steel plate group and the memory alloy embracing device group were significantly better than the T-shaped plate group at two weeks after operation. Satisfactory clinical results can be obtained by using T-shaped plate, double-miniature steel plate and memory alloy embracing device in the treatment of Edinburgh IB fracture of proximal clavicle. However, the double-miniature steel plate group has the advantages of small incision, low cost, and quick postoperative recovery, and has more early advantages.

Study on shape memory alloy embracing fixator in treatment of the proximal clavicle fracture.

This study was designed to investigate the application value of shape memory alloy embracing fixator in the treatment of proximal clavicle fracture. From April 2018 to October 2020, the fracture data of patients with proximal clavicle fractures treated with shape memory alloy embracing fixator were retrospectively analyzed, including 12 males and 8 females. The age of patients ranged from 34 to 66 years (mean, 43.4 years). According to Craig's classification, the patients were divided into the following groups: type CII (eight cases), type CIII (five cases), type CⅤ (seven cases), all of which were closed fractures without nerve or vascular injury. The fracture healing time and postoperative complications were observed, and the shoulder joint function was evaluated by Constant score. All patients were followed up for 13-19 months (average 15.6 months). The clavicle radiographs showed that all the 20 patients had bone union, and the fracture union time was 6-10 months (average 7.2 months). There were no complications such as internal fixation fracture and displacement. According to the Constant criterion, 13 cases were excellent and 5 cases were fair and 1 case was good. The treatment of proximal clavicle fracture with shape memory alloy embracing fixator is an effective treatment method with simple operation with satisfactory fixation effect and low complication rate, which is worthy of being widely used in clinical practice.

Clinical effect of 'Fast-track Management' guided by ERAS concept under the multi-disciplinary cooperation mode of femoral intertrochanteric fracture in the elderly.

The article was designed to explore the clinical efficacy of 'Fast-track Management' guided by ERAS concept under the multidisciplinary collaboration model for early operation of femoral intertrochanteric fracture in the elderly. The clinical data of 198 intertrochanteric fracture in the elderly were retrospectively analyzed. According to the diagnosis and treatment mode, they were divided into cooperative group and routine group. The preoperative waiting time, preoperative deep venous thrombosis, operation time, intraoperative bleeding, hospitalization time, Harris score, VAS score, intervention effect of eras concept, complication occurrence, and 1-year mortality were made a comparison. There were notable differences in the preoperative waiting time, the number of cases of preoperative deep vein thrombosis and the length of hospital stay between the cooperative group and routine group. The incidence of complications in the cooperative group was 9.38%, which was significantly lower than that in the conventional group, 54.90%. The 1-year mortality rate was clearly lower in the cooperative group than in the routine group. At 1 and 2 weeks after operation, VAS, HAMA and PSQI of the cooperative group were lower, but Harris and Barthel were higher than the routine group. At 1 month after operation, there was no clear difference in VAS and Harris between the cooperative group and routine group. The establishment of 'Fast-track Management' based on ERAS concept in the multidisciplinary collaboration model can effectively alleviate the pain of femoral intertrochanteric fracture in the elderly, shorten the hospital stay, reduce the occurrence of postoperative complications and the mortality within 1 year.

Cervical vagal nerve schwannoma induced arrhythmia: a rare case report and literature review.

BACKGROUND: Schwannomas are benign tumors deriving from the sheath of cranial and peripheral nerves. The vagus nerve is comprised of a complex neuro-endocrine-immune network that maintains homeostasis, most tracts of it play a role in parasympathetic activity. We present an example of a rare cervical vagal schwannoma case accompanied by arrhythmia. CASE PRESENTATION: A 35-year-old female patient with a left cervical vagus schwannoma and ventricular arrhythmia underwent schwannoma resection in the operating room. The patient's suppressed heart rate increased after tumor removal, and the cardiac rhythm returned to normal postoperatively. Pathological examination demonstrated the diagnosis of schwannoma. CONCLUSIONS: This case explains the link between the vagus nerve and the cardiovascular system, proving that a damaged cervical vagus nerve can inhibit the heart rate and lead to arrhythmias, and eventually requiring surgical intervention.

Early-Stage Geopolymerization Process of Metakaolin-Based Geopolymer.

The geopolymerization of aluminosilicate materials in alkaline environments is a complex physicochemical process that greatly influences the microstructure and engineering performances. This work aims to reveal the geopolymerization process of metakaolin-based geopolymer (MKG) in the first 5 d. Physicochemical characteristics of different evolution stages are disposed of in chronological order. The evolutions of electrical resistivity, dehydration process, volume deformation, and ionic concentration are comprehensively analyzed. Results show that chemical dissolution produces large dismantled fragments rather than small free monomers. The formation of a solid matrix follows the "spatial filling rule", which means that gels grow by locking swelling fragments to form a framework, then densely filling residual space. Based on chemical models, early geopolymerization of MKG can be divided into six stages from the physicochemical perspective as dismantling, locking fixation, free filling, limited filling, second dissolution, and local mending. Those findings expand the understanding of the phase evolution of the early geopolymerization process; thus, the microstructure of MKG can be better manipulated, and its engineering performances can be improved.

Incidence and risk of hypertension with lenvatinib in treatment of solid tumors: An updated systematic review and meta-analysis.

This meta-analysis was performed to assess the relationship between Lenvatinib use for malignancy and hypertension (HTN). A total of 2483 patients met inclusion criteria. The relative risk (RR) for all-grade and high-grade (≧3) HTN were 2.61 (p ≦ .001) and 3.35 (p≦ .001), respectively, for Lenvatinib compared with other multitarget tyrosine kinase inhibitors or placebo. The cumulative incidence of all-grade and high-grade HTN was 70% and 34%, respectively. The studies with median treatment duration (TD) longer than 7.4 months demonstrated a higher incidence of high-grade HTN than studies with shorter TD (34% vs 28%). The incidence of all levels of HTN increased with TD (68% vs 49%). Trials with median progression-free survival (PFS) longer than nine months had a higher incidence of both all-grade (37% vs 28%) and high-grade (71% vs 48%) HTN. Lenvatinib, a drug commonly used in cancer treatment, is a risk factor for the development of HTN. A longer duration of Lenvatinib treatment was associated with higher frequency of HTN. Further investigation for Lenvatinib of the association between the occurrence of HTN and prognosis will be warranted.

Endovascular therapy for distal hilar renal artery aneurysm: a case report and literature review.

Renal artery aneurysm (RAA), a type of visceral aneurysm with atypical symptoms, is difficult to detect and is usually discovered incidentally by imaging examination. Hilar RAA (HRAA) represents a relatively rare subgroup of RAA that is located in the distal part of the renal artery, close to the renal parenchyma. We reported a 55-year-old woman with an HRAA measuring 19 mm × 20 mm × 20 mm. She underwent endovascular therapy with bare-metal stent implantation with nested coil embolization. She was discharged without complications. The uniqueness of this case is the aneurysm location, which was at the distal right renal artery, making it difficult to preserve the blood supply to the right kidney. The novelty of the minimally invasive technique was that this endovascular treatment not only eliminated the aneurysm, but also preserved the blood supply to the ipsilateral kidney. Endovascular therapy is effective in the management of HRAA.

Clinical study of lenvatinib in the treatment of hepatitis virus-related hepatocellular carcinoma and antiviral therapy.

Background: Lenvatinib is recommended as a first-line tyrosine kinase inhibitor for advanced hepatocellular carcinoma (HCC) since 2017. The aim of this study was to compare the clinical action of lenvatinib in hepatitis B virus (HBV)-related HCC and hepatitis C virus (HCV)-related HCC. Methods: A continuous cohort of advanced HCC was retrospectively enrolled. And the patients were divided into HBV-related HCC and HCV-related HCC based on previous history of hepatitis virus infection. Then propensity score matching (PSM) was conducted to compare objective response rate (ORR),disease control rate (DCR),progression-free survival (PFS),overall survival (OS) and safety between the two groups. Results: A total of 203 eligible patients were included, with 72 HBV-related HCC and 36 HCV-related HCC after PSM. Both ORR (20.8% vs. 5.6%, P = .0759) and DCR (76.4% vs. 52.8%, P = .0232) were significantly higher in the HBV-related HCC than in the HCV-related HCC. Although no statistical differences in PFS (6.1 months vs. 3.3 months, P = .17) and OS (14.9 months vs. 17.7 months, P = .96) were observed between the two groups, there was a trend of difference in the PFS survival curve. On multivariate regression analysis of PFS, both HBV infection (HR, .54; 95% CI, .31-.95; P = .0332) and antiviral time >5 years (HR, .49; 95% CI, .26-.9; P = .0219) were identified as independent favorable factors, and AFP >200 ng/mL (HR, 1.88; 95% CI, 1.1-3.22; P = .0216) were found to be an independent adverse factor. In addition, compared with HCC who received the first dose of antiviral drugs less than 5 years, the patients who were administered those drugs over 5 years had a significantly favorable PFS (11.27 months vs. 3.87 months, P = .0011). Lenvatinib was well tolerated in all patients and the adverse events (AEs) were similar between the two groups. Conclusion: It seemed that lenvatinib benefited more in HBV-related advanced HCC in delaying disease progression, compared to those with HCV-related advanced HCC.

Current Status and Prospect of Stent Placement for May-Thurner Syndrome.

Stent implantation has been proven to be safe and has become the first-line intervention for May-Thurner syndrome (MTS), with satisfactory mid-term patency rates and clinical outcomes. Recent research has demonstrated that catheter-directed thrombolysis is the preferred strategy when MTS is combined with deep vein thrombosis after self-expanding stent placement. However, the stent used for the venous system was developed based on the experience obtained in the treatment of arterial disease. Consequently, relatively common corresponding complications may come along later, which include stent displacement, deformation, and obstruction. Different measures such as adopting a stent with a larger diameter, improving stent flexibility, and increasing stent strength have been employed in order to prevent these complications. The ideal venous stent is presently being evaluated and will be introduced in detail in this review.

Pathophysiologic Role of Molecules Determining Arteriovenous Differentiation in Adult Life.

The structural differences between arteries and veins are genetically predetermined. Vascular identity markers, the molecular markers specific to veins and arteries, determine the differential development of vessels during embryogenesis and their expression persists in adult vessels. It is revealed that they can be reactivated under various pathophysiologic conditions even after vessel differentiation. Thus, once considered as quiescent in adults, vascular identity markers may actually play significant roles in vascular remodeling. Manipulation of vascular identity and the underlying molecular mechanisms might be a novel strategy to improve vascular remodeling for clinical application.

Comparison of four different internal fixation methods in the treatment of distal clavicle fractures.

This study compared the clinical efficacy of four internal fixation methods in the treatment of distal clavicle fractures, in an effort to guide appropriate selection and application in the clinic. Eighty-four patients with distal clavicle-comminuted fractures were treated with a distal clavicle anatomic plate (group A), clavicular hook plate (group B), double-plate vertical fixation (group C), or T-shaped steel plate internal fixation (group D). The Constant-Murley scoring system was used to evaluate the shoulder joint function. The fracture healing time, VAS, and postoperative complications were compared and analyzed among the four groups. According to the Constant-Murley evaluation standard, the excellent and good rates of the four groups were 94.4, 73.1, 95 and 80% in groups A-D, respectively. The excellent and good rates of Constant-Murley evaluation standard in groups A and C were significantly better than those in groups B and D (P<0.05). VAS in the distal clavicle anatomic plate group (group A), double-plate vertical fixation group (group C), and T-shaped steel plate internal fixation group (group D) were significantly better than the clavicular hook plate group (group B) (P<0.05). The incidence of postoperative complications in the clavicular hook plate group (group B) was 15.4% and in the T-shaped steel plate internal fixation group (group D) was 15%, which were significantly higher than those of the distal clavicle anatomic plate group (group A) and double-plate vertical internal fixation group (group C) (P<0.05). The treatment of distal clavicle fractures using either one of the four internal fixation techniques can obtain better clinical results. The distal clavicle anatomic plate and double-plate vertical internal fixation techniques are associated with a decreased incidence of shoulder pain, an increase in the range of motion of the shoulder, and a reduction in complications, and thus, are preferable for the early functional recovery of limbs.

Clavicle hook plate versus distal clavicle locking plate for Neer type II distal clavicle fractures.

BACKGROUND: The purpose of this meta-analysis was to compare clavicle hook plates versus distal clavicle locking plates for the treatment of Neer type II distal clavicle fractures. METHODS: PubMed (1996 to January 2019), Embase (1980 to January 2019), Web of Science (1990 to January 2019), the Cochrane Library (January 2019), and the China National Knowledge Infrastructure (January 2019) were systematically searched without language restrictions for literature retrieval. The Constant-Murley shoulder joint function score at 3 and 6 months after the operation and the postoperative complications after the operation (shoulder joint pain, abduction restriction, fracture delay healing, subacromial impingement) were the outcomes. Stata 12.0 was used for the meta-analysis. RESULTS: A total of 9 clinical trials involving 446 patients were finally included in this meta-analysis. The results showed that the improvement in the Constant-Murley shoulder joint function score in the distal locking plate group was better than that in the clavicle hook plate group at 3 and 6 months after the operation (P < 0.05). There were fewer cases of shoulder joint pain and restricted shoulder abduction range of motion in the distal locking plate group, and the difference was statistically significant (P < 0.05). There were no statistically significant differences in fracture delay healing and subacromial impingement between the two groups (P > 0.05). CONCLUSION: Compared with the clavicular hook plate, the distal clavicle locking plate for the treatment of Neer type II distal clavicle fractures is associated with better shoulder function recovery and fewer complications related to pain and abduction restriction.