Enantioselective Synthesis of Bispiro[indanedione-oxindole-cyclopropane]s through Organocatalytic [2+1] Cycloaddition.

A series of compounds featuring a novel bispiro[indanedione-oxindole-cyclopropane] moiety have been synthesized through a squaramide-catalyzed [2+1] cycloaddition reaction. The tandem Michael-alkylation reaction of 2-arylidene-1,3-indanediones with 3-bromooxindoles furnished the cycloadducts in high yields with excellent diastereo- and enantioselectivities. The ammonium ylide in the catalytic process, as a key intermediate, was revealed by the high-resolution mass spectrometry study.

Effect of Different Types of Ossification of the Posterior Longitudinal Ligament on the Dynamic Biomechanical Response of the Spinal Cord: A Finite Element Analysis.

Ossification of the posterior longitudinal ligament (OPLL) has been identified as an important cause of cervical myelopathy. However, the biomechanical mechanism between the OPLL type and the clinical characteristics of myelopathy remains unclear. The aim of this study was to evaluate the effect of different types of OPLL on the dynamic biomechanical response of the spinal cord. A three-dimensional finite element model of the fluid-structure interaction of the cervical spine with spinal cord was established and validated. The spinal cord stress and strain, cervical range of motion (ROM) in different types of OPLL models were predicted during dynamic flexion and extension activity. Different types of OPLL models showed varying degrees of increase in stress and strain under the process of flexion and extension, and there was a surge toward the end of extension. Larger spinal cord stress was observed in segmental OPLL. For continuous and mixed types of OPLL, the adjacent segments of OPLL showed a dramatic increase in ROM, while the ROM of affected segments was limited. As a dynamic factor, flexion and extension of the cervical spine play an amplifying role in OPLL-related myelopathy, while appropriate spine motion is safe and permitted. Segmental OPLL patients are more concerned about the spinal cord injury induced by large stress, and patients with continuous OPLL should be noted to progressive injuries of adjacent level.

Potential of electronic devices for detection of health problems in older adults at home: A systematic review and meta-analysis.

OBJECTIVE: The aim of this review was to evaluate the overall diagnostic performance of e-devices for detection of health problems in older adults at home. METHODS: A systematic review was conducted following the PRISMA-DTA guidelines. RESULTS: 31 studies were included with 24 studies included in meta-analysis. The included studies were divided into four categories according to the signals detected: physical activity (PA), vital signs (VS), electrocardiography (ECG) and other. The meta-analysis showed the pooled estimates of sensitivity and specificity were 0.94 and 0.98 respectively in the 'VS' group. The pooled sensitivity and specificity were 0.97 and 0.98 respectively in the 'ECG' group. CONCLUSIONS: All kinds of e-devices perform well in diagnosing the common health problems. While ECG-based health problems detection system is more reliable than VS-based ones. For sole signal detection system has limitation in diagnosing specific health problems, more researches should focus on developing new systems combined of multiple signals.

Asymmetric Formal (3 + 2) Cyclocondensation of Coumarin-3-Formylpyrazoles as 3-Carbon Partners with 3-Hydroxyoxindoles via Esterification/Michael Addition Sequence.

The first enantioselective formal (3 + 2) cyclocondensation involving α,ß-unsaturated pyrazoleamides as 3-carbon partners was accomplished in a stepwise fashion. The stepwise esterification/Michael addition sequence is promoted by Zn(OTf)2 and quinine-squaramide derivative, respectively. The protocol enables access to spiro-fused pentacyclic spirooxindoles from coumarin-3-formylpyrazoles and 3-hydroxyoxindoles in good to satisfactory overall yields (up to 91%) with excellent dr (all cases >20:1 dr) and high ee values (up to 99%). Mechanistic investigations contributed to shedding light on the enantioselective event of the process.

Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense.

Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (±)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.

[Randomized Controlled Trial of the Effects of Repetitive Transcranial Magnetic Stimulation and Mirror Therapy on Phantom Limb Pain in Amputees].

Objective: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on phantom limb pain (PLP) in amputees, and to compare the therapeutic effect with that of mirror therapy (MT). Methods: The study was designed as a randomized controlled trial. The evaluators were blinded, while the subjects and the therapists were unblinded. Subjects were randomly assigned to either the rTMS group or the MT group with a computer-generated random number table. From June 2018 to December 2020, from out of 45 amputee patients screened for the study, 30 who met the inclusion criteria were recruited for the study. All patients were recruited from the Rehabilitation Medicine Center, West China Hospital, Sichuan University. In the end, 4 patients withdrew from the study and 26 patients (12 in the rTMS group and 14 in the MT group) completed the prescribed treatment and evaluation. The rTMS group was given rTMS (1 Hz, 15 min, 5 d/week) for 2 weeks in addition to conventional rehabilitation therapy, while the MT group received MT (corresponding movements of limbs, 15 min, 5 d/week) for 2 weeks in addition to conventional rehabilitation therapy. PLP was evaluated by the Visual Analogue Scale (VAS) and Douleur Neuropathique 4 Questions (DN-4). Subjects were assessed before treatment ( t 0), immediately after the completion of the treatment ( t 1) and 3 months after the completion of the treatment ( t 2). Results: The mean age of the 26 patients was 39.73±12.64. There were 15 males and 11 females. According to the reported description of the characteristics of the PLP by the patients, the characteristics with the highest incidence were tingling, stabbing, numbing, electric shocks and burning in descending order. There was no significant difference in the incidence of PLP characteristics between the two groups ( P>0.05). The two groups had comparable baseline data, showing no significant difference in VAS and DN-4 between the two groups at t 0 ( P>0.05). At t 1 and t 2, the VAS and DN-4 scores were decreased from those of t 0, showing statistically significant difference in both groups ( P<0.01 for both scores). In the rTMS group, there was no significant difference between VAS and DN-4 scores at t 1 and those at t 2 ( P>0.05). In the MT group, the VAS and DN-4 scores at t 2 were significantly lower than those of t 1 ( P<0.05). There was no statistically significant difference between the rTMS group and MT group in the changes in pain measurements, i.e., VAS and DN-4 scores, before and after the intervention ( P>0.05). The 26 patients who completed the experiment showed no dizziness, headache, or other abnormalities during the study. Conclusion: The results of this study indicate that repetitive transcranial magnetic stimulation could improve PLP in amputees, and the improvement effect was comparable to that of mirror therapy.

Research progress on the treatment of advanced prostate cancer with Olaparib.

Prostate cancer (PCa) is one of the most common malignancies in men worldwide, and metastatic castrate-resistant prostate cancer (mCRPC) has shown a poor prognosis. Although chemotherapy and androgen deprivation therapy (ADT) have improved clinical outcomes, the median survival (MS) of patients with mCRPC is still less than 2 years. With the development of poly adenosine diphosphate-ribose polymerase inhibitor (PARPi), the treatment strategy for patients with mCRPC has markedly evolved. Olaparib, a type of PARPi that can selectively induce synthetic lethality in cancer cells with homologous recombination (HR) deficiencies, was the first type of PARPi approved for treating patients with mCRPC harboring mutations in HR repair (HRR) genes. This review discusses and summarizes the latest progress on therapeutic mechanisms, monotherapy, combination therapy, and adverse events of Olaparib.

Impact Behavior of Hydrophilic Micron Particles on a Planar Gas-Liquid Interface.

The behavior of hydrophilic micron particles impacting on the gas-liquid interface has been further experimentally studied using a high-speed camera at different surface tensions and dynamic viscosities of liquids. The results show that the impact behavior exhibits suspension and submergence modes, whose boundary cannot be clearly identified because the overlap between the impact velocity ranges occurs because of the unstable pinning of the three-phase contact line on the surface of hydrophilic particles. The liquid properties have little effect on the wettability of hydrophilic particles but greatly influence the hydrodynamic and capillary force exerted on the particles, leading to the expansion of the suspension mode range. In addition, the penetration probability changes little with the decrease in surface tension, while it significantly reduces with the increase in dynamic viscosity. A penetration probability model is predicted as an exponential function of the inertial and supporting forces, and the experimental values agree well with the predicted values. The outcomes of this research will be helpful for understanding the mechanism of particle-interface interaction and providing guidance for enhancing the separation of hydrophilic fine ash via a bubble scrubbing system.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases: A case report.

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Finite element modeling and analysis of effect of preexisting cervical degenerative disease on the spinal cord during flexion and extension.

Recent studies have emphasized the importance of dynamic activity in the development of myelopathy. However, current knowledge of how degenerative factors affect the spinal cord during motion is still limited. This study aimed to investigate the effect of various types of preexisting herniated cervical disc and the ligamentum flavum ossification on the spinal cord during cervical flexion and extension. A detailed dynamic fluid-structure interaction finite element model of the cervical spine with the spinal cord was developed and validated. The changes of von Mises stress and maximum principal strain within the spinal cord in the period of normal, hyperflexion, and hyperextension were investigated, considering various types and grades of disc herniation and ossification of the ligamentum flavum. The flexion and extension of the cervical spine with spinal canal encroachment induced high stress and strain inside the spinal cord, and this effect was also amplified by increased canal encroachments and cervical hypermobility. The spinal cord might evade lateral encroachment, leading to a reduction in the maximum stress and principal strain within the spinal cord in local-type herniation. Although the impact was limited in the case of diffuse type, the maximum stress tended to appear in the white matter near the encroachment site while compression from both ventral and dorsal was essential to make maximum stress appear in the grey matter. The existence of canal encroachment can reduce the safe range for spinal cord activities, and hypermobility activities may induce spinal cord injury. Besides, the ligamentum flavum plays an important role in the development of central canal syndrome.Significance. This model will enable researchers to have a better understanding of the influence of cervical degenerative diseases on the spinal cord during extension and flexion.

The biomechanical effect of different types of ossification of the ligamentum flavum on the spinal cord during cervical dynamic activities.

Ossification of the ligamentum flavum (OLF) is thought to be an influential etiology of myelopathy, as thickened ligamentum flavum causes the stenosis of the vertebral canal, which could subsequently compress the spinal cord. Unfortunately, there was little information available on the effects of cervical OLF on spinal cord compression, such as the relationship between the progression of cervical OLF and nervous system symptoms during dynamic cervical spine activities. In this research, a finite element model of C1-C7 including the spinal cord featured by dynamic fluid-structure interaction was reconstructed and utilized to analyze how different types of cervical OLF affect principal strain and stress distribution in spinal cord during spinal activities towards six directions. For patients with cervical OLF, cervical extension induces higher stress within the spinal cord among all directions. From the perspective of biomechanics, extension leads to stress concentration in the lateral corticospinal tracts or the posterior of gray matter. Low energy damage to the spinal cord would be caused by the high and fluctuating stresses during cervical movements to the affected side for patients with unilateral OLF at lower grades.

Acupoint catgut embedding improves learning and memory impairment in vascular dementia rats.

Background: Vascular dementia (VD) is a disease that affects brain function through cerebrovascular disease. Due to its complex pathogenesis, there is no effective drug treatment for VD. The present study aimed to evaluate the role of acupoint catgut embedding in the treatment of rats with VD and its possible molecular mechanism. Methods: A modified 4 vessel occlusion (4-VO) method was used to establish a VD model rat, and spatial learning and memory ability was assessed using the Morris water maze (MWM) test. The protein expression levels were detected by Western blot. Hematoxylin and eosin (HE) staining was used for histological analysis and enzyme-linked immunosorbent assay (ELISA) was applied for analysis of serum inflammatory factors. Results: We successfully constructed VD model rats with spatial learning and memory impairment, hippocampus injury, and high inflammatory response. Treatment of VD rats with acupoint catgut embedding significantly reduced escape latency and increased the time in the target quadrant and platform crossing times. VD-mediated hippocampal tissue damage and inflammatory reaction [down-regulating interleukin-1ß (IL-1ß), interleukin-6 (IL-6)] were significantly alleviated by acupoint catgut embedding treatment. In addition, further mechanism exploration found that acupoint catgut embedding treatment could improve the activity of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. In summary, acupoint catgut embedding treatment improved spatial learning and memory loss, alleviated pathological damage of the hippocampus, and inhibited inflammation response in VD rats, which was probably related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway. Conclusions: Acupoint catgut embedding may warrant further study as an adjuvant therapy for the treatment of VD.

Biomechanical response of lumbar intervertebral disc in daily sitting postures: a poroelastic finite element analysis.

This study aims to establish and validate a poroelastic L4-L5 finite element model to evaluate the effect of different sitting postures and their durations on the mechanical responses of the disc. During the sustained loading conditions, the height loss, fluid loss and von-Mises stress gradually increased, but the intradiscal pressure decreased. The varying rates of aforementioned parameters were more significant at the initial loading stage and less so at the end. The predicted values in the flexed sitting posture were significantly greater than other postures. The extended sitting posture caused an obvious von-Mises stress concentration in the posterior region of the inter-lamellar matrix. From the biomechanical perspective, prolonged sitting may pose a high risk of lumbar disc degeneration, and therefore adjusting the posture properly in the early stage of sitting time may be useful to mitigate that. Additionally, upright sitting is a safer posture, while flexed sitting posture is more harmful.

Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

OBJECTIVE: The aim of this meta-analysis was to summarize the available results of immunotherapy predictors for small cell lung cancer (SCLC) and to provide evidence-based information for their potential predictive value of efficacy. METHODS: We searched PubMed, EMBASE, Web of Science, The Cochrane Library, and ClinicalTrials (from January 1, 1975 to November 1, 2021). The hazard ratios (HR) and its 95% confidence intervals (CIs) and tumor response rate of the included studies were extracted. RESULTS: Eleven studies were eventually included and the pooled results showed that programmed cell death ligand 1 (PD-L1) positive: objective response rate (ORR) (relative risk [RR] = 1.39, 95% CI [0.48, 4.03], p = 0.54), with high heterogeneity (p = 0.05, I2  = 56%); disease control rate [DCR] (RR = 1.31, 95% CI [0.04, 38.57], p = 0.88), with high heterogeneity (p = 0.04, I2  = 75%); overall survival (OS) (HR = 0.89, 95% CI [0.74, 1.07], p = 0.22); and progression-free survival (PFS) (HR = 0.83, 95% CI [0.59, 1.16], p = 0.27), with high heterogeneity (p = 0.005, I2  = 73.1%). TMB-High (TMB-H): OS (HR = 0.86, 95% CI [0.74, 1.00], p = 0.05); PFS (HR = 0.71, 95% CI [0.6, 0.85], p < 0.001). Lactate dehydrogenase (LDH) >upper limit of normal (ULN): OS (HR = 0.95, 95% CI [0.81, 1.11], p = 0.511). Asian patients: OS (HR = 0.87, 95% CI [0.72, 1.04], p = 0.135); White/Non-Asian patients: OS (HR = 0.83, 95% CI [0.76, 0.90], p < 0.001). Liver metastasis patients: OS (HR = 0.93, 95% CI [0.83, 1.05], p = 0.229); PFS (HR = 0.84, 95% CI [0.67, 1.06], p = 0.141). Central nervous system (CNS) metastasis patients: OS (HR = 0.91, 95% CI [0.71, 1.17], p = 0.474); PFS (HR = 1.03, 95% CI [0.66, 1.60], p = 0.903). CONCLUSION: The available research results do not support the recommendation of PD-L1 positive and TMB-H as predictors for the application of immune checkpoint inhibitors (ICIs) in SCLC patients. LDH, baseline liver metastasis and CNS metastasis may be used as markers/influencing factors for predicting the efficacy of ICIs in SCLC patients. Non-Asian SCLC patients had better efficacy with ICIs in our results.

Cutaneous metastasis from esophageal squamous cell carcinoma: A case report.

BACKGROUND: Esophageal cancer is a common cause of cancer-related death worldwide. Cutaneous metastasis of esophageal squamous cell carcinoma is rare, particularly in diffuse skin metastasis. CASE SUMMARY: In this case report, we describe an 82-year-old male who was diagnosed with esophageal squamous cell carcinoma. The tumor was staged as T4N3M1 (Stage IVB). The pathological findings revealed poorly differentiated squamous cell carcinoma of the esophagus. Four months after diagnosis, the patient began chemotherapy, and symptoms were relieved after four cycles of chemotherapy. After that, the patient returned home without a systematic physical examination. One year after diagnosis, the patient realized that the skin of the abdominal wall was hard and rough without pain, and the color became darker than normal skin. Thirteen months after diagnosis, a biopsy of the patient's abdominal lesion revealed that the skin metastasis was derived from the esophagus. Then the patient received two cycles of apatinib combined with docetaxel, but the abdominal lesion worsened. Two cycles of nivolumab were administered, but the patient eventually died of multiple organ failure. CONCLUSION: This report highlights cutaneous metastasis as a late and untreatable metastasis of esophageal cancer.

Diagnosis and guidance of treatment of breast cancer cutaneous metastases by multiple needle biopsy: A case report.

BACKGROUND: Breast cancer patients have a high skin metastasis rate. However, reports on treatment of cutaneous metastases of breast cancer are scarce. CASE SUMMARY: We report the treatment process for one breast cancer case with bone, lung, and skin metastases. The patient was a 43-year-old woman with advanced breast cancer and skin metastasis. She underwent pathological diagnosis by needle biopsy to guide the treatment. When the disease progressed, a new pathological diagnosis was determined by needle biopsy to guide the treatment. The patient received chemotherapy, endocrine therapy, and photodynamic dynamic therapy, followed by sonodynamic therapy. CONCLUSION: Repeated puncture should be performed for advanced breast cancer with skin metastasis, in order to obtain the pathology and directly determine diagnosis when the disease progresses. The treatment should focus on controlling the systemic metastasis, rather than the local disease.

Biomechanical effect of age-related structural changes on cervical intervertebral disc: A finite element study.

Previous literature has investigated the biomechanical response of healthy and degenerative discs, but the biomechanical response of suboptimal healthy intervertebral discs received less attention. The purpose was to compare the biomechanical responses and risk of herniation of young healthy, suboptimal healthy, and degenerative intervertebral discs. A cervical spine model was established and validated using the finite element method. Suboptimal healthy, mildly, moderately, and severely degenerative disc models were developed. Disc height deformation, range of motion, intradiscal pressure, and von Mises stress in annulus fibrosus were analyzed by applying a moment of 4 Nm in flexion, extension, lateral bending, and axial rotation with 100 N compressive loads. Disc height deformation in young healthy, suboptimal healthy, mildly, moderately, and severely degenerative discs was 40%, 37%, 21%, 12%, and 8%, respectively. The decreasing order of the range of motion was young healthy spine > suboptimal healthy spine > mildly degenerative spine > moderately degenerative spine > severely degenerative spine. The mean stress of annulus ground substance in the suboptimal healthy disc was higher than in the young healthy disc. The mean stress of inter-lamellar matrix and annulus ground substance in moderately and severely degenerative discs was higher than in other discs. Age-related structural changes and degenerative changes increased the stiffness and reduced the elastic deformation of intervertebral discs. Decreased range of motion due to the effects of aging or degeneration on the intervertebral disc, may cause compensation of adjacent segments and lead to progressive degeneration of multiple segments. The effect of aging on the intervertebral disc increased the risk of annulus fibrosus damage from the biomechanical point of view. Moderately and severely degenerative discs may have a higher risk of herniation due to the higher risk of damage and layers separation of annulus fibrosus caused by increased stress in the annulus ground substance and inter-lamellar matrix.

Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway.

OBJECTIVE: To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD). METHODS: The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA. RESULTS: Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P<0.05 or P<0.01), and led to neuronal repair in the hippocampus. There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups, nor between the 4-VO+TAK-242 and 4-VO+EA groups (P>0.05). CONCLUSIONS: EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

Effect of home-based exercise programs with e-devices on falls among community-dwelling older adults: a meta-analysis.

Aim: To explore the effectiveness of home-based exercise programs with e-devices (HEPEs) on falls among community-dwelling older adults. Methods: Twelve randomized controlled trials were included in the meta-analysis considering four fall-related outcomes. Results: HEPEs significantly reduced the rate of falls (risk ratio: 0.82; 95% CI: 0.72-0.95; p = 0.006) and improved lower extremity strength (mean difference: -0.94; 95% CI: -1.71 to -0.47; p < 0.001). There was a significant improvement favoring HEPEs on balance if the participants were aged >75 years (mean difference: -0.55; 95% CI: -1.05 to -0.05; p = 0.03), or the intervention duration was at least 16 weeks (mean difference: -0.81; 95% CI: -1.58 to -0.05; p = 0.04). Conclusion: HEPEs demonstrated an overall positive effect on falls among community-dwelling older adults.

Meta-analysis of gemcitabine plus nab-paclitaxel combined with targeted agents in the treatment of metastatic pancreatic cancer.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GA) is a commonly used first-line treatment regimen for metastatic pancreatic cancer, and many studies will add a novel targeted agent to this regimen for improving patient survival rate. However, the clinical effectiveness of GA is the most controversial issue. AIM: To compare the efficacy and safety of GA regimen with a targeted agent and GA regimen. METHODS: Up to 1 December 2021, the eligible randomized controlled trials (RCTs) relating to GA and GA with a targeted agent were searched on PubMed, EMBASE and Cochrane Library for eligible data. We screened out appropriate studies for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and toxicity, which had been pooled and finally analyzed by using Stata version 15.1. In addition, we use Reference Citation Analysis (https://www.referencecitationanalysis.com/) to collect the latest related literature to improve the latest cutting-edge research results. RESULTS: Seven RCTs involving 1544 patients (848 men and 696 women) were included. There were no significant differences between GA with a targeted agent and GA in PFS [hazard ratio (HR): 1.18 95% confidence interval (CI): 0.91-1.53], OS (HR: 1.12 95%CI: 0.99-1.27), and ORR (HR: 0.96 95%CI: 0.71-1.29). There was no notable difference in the two groups in grade 3/4 toxicity (fatigue, anemia, vomiting and neutropenia), whereas the incidence of grade 3/4 diarrhea considerably increased in GA with a targeted drug. CONCLUSION: Adding a novel targeted agent to the GA regimen did not improve survival rate of patients with metastatic pancreatic cancer.