Concomitant use of renin-angiotensin system inhibitors augments the efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: The impact of renin-angiotensin system inhibitors (RASIs) on the outcome of hypertensive cancer patients undergoing immune checkpoint inhibitor (ICIs) therapy remains ambiguous. This investigation sought to elucidate the consequences of RASIs use on the prognosis for this specific patient group within the context of ICIs treatment, aspiring to provide a clearer basis for rational, evidence-driven choices in the clinical prescription of these medications. Methods: A comprehensive search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library for original studies published up to 6 August 2023. Studies published in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. All statistical analyses were executed utilizing R software (version 4.2.2). Results: A total of 13 studies, encompassing approximately 12,595 patients, satisfied the inclusion criteria. Meta-analyses demonstrated a statistically significant association between the use of RASIs and a favorable outcome in OS (HR, 0.74; 95% CI, 0.62-0.88) and PFS (HR, 0.77; 95% CI, 0.62-0.96) among cancer patients receiving ICIs treatment. Conclusion: This investigation provides compelling evidence supporting the beneficial prognostic impact of RASIs on cancer patients receiving ICIs. RASIs present a viable option as antihypertensive agents for cancer patients with hypertension undergoing ICIs treatment. Further exploration and validation through prospective studies are necessary to establish definitive guidelines for the use of RASIs in managing hypertensive cancer patients undergoing immunotherapy with ICIs. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023454886.

Influence of physicians' seniority on efficacy of silver needle therapy for low back fasciitis: A prospective, cohort study.

BACKGROUND: Physicians' seniority has always been the focus of patients. Silver needle therapy (SNT) has been applied for more than 60 years. It is similar to moxibustion and has a good therapeutic effect on soft tissue pain. This study aimed to determine the influence of physicians' seniority on the efficacy of SNT for patients with low back fasciitis. METHODS: This was a prospective cohort study at the Affiliated Hospital of Qingdao University. Patients diagnosed with low back fasciitis were split into junior physician (JP) and senior physician (SP) groups (n = 30) based on the seniority of the physician. The numerical rating scale (NRS) was administered during the SNT, and operation time was recorded. The NRS, Oswestry Disability Index (ODI), and Short-Form 12 of quality of life (SF-12) scores at 1, 2, 6, and 12 months after the treatment and autonomic nervous system (ANS) activity were also observed. RESULTS: Compared with the SP group, the NRS score during the SNT (5.20 ±â€…0.71 vs 2.53 ±â€…0.94) and operation time (11.7 ±â€…1.6 minutes vs 6.8 ±â€…1.1 minute) were higher in the JP group (P < .05). The NRS, ODI score, SF-12 score, and ANS activity after treatment were not significantly different between SP and JP groups. Additionally, in the multivariate linear regression analysis model, the physicians' seniority was an independent factor affecting the NRS score during the SNT and operation time (P < .05). CONCLUSION: SNT could attenuate the pain of patients with low back fasciitis in the short and long term without severe complications. The physicians' seniority did not influence the efficacy of SNT, but the JP group showed an increased operation time and a higher degree of pain during the operation.

Comparison of Inflation and Ventilation with Hydrogen Sulfide during the Warm Ischemia Phase on Ischemia-Reperfusion Injury in a Rat Model of Non-Heart-Beating Donor Lung Transplantation.

Donor lung ventilation and inflation during the warm ischemia could attenuate ischemia-reperfusion injury (IRI) after lung transplantation. Hydrogen sulfide (H2S), as a kind of protective gas, has demonstrated the antilung IRI effect. This study is aimed at observing the different methods of administering H2S in the setting of warm ischemia, ventilation, and inflation on the lung graft from a rat non-heart-beating donor. After 1 h of cardiac arrest, donor lungs in situ were inflated with 80 ppm H2S (FS group), ventilated with 80 ppm H2S (VS group), or deflated (control group) for 2 h. Then, the lung transplantation was performed after 3 h cold ischemia. The rats without ischemia and reperfusion were in the sham group. Pulmonary surfactant in the bronchoalveolar lavage fluid was measured in donor lung. The inflammatory response, cell apoptosis, and lung graft function were assessed at 3 h after reperfusion. The lung injury was exacerbated in the control group, which was attenuated significantly after the H2S treatment. Compared with the FS group, the pulmonary surfactant in the donor was deteriorated, the lung oxygenation function was decreased, and the inflammatory response and cell apoptosis were increased in the graft in the VS group (P < 0.05). In conclusion, H2S inflation during the warm ischemia phase improved the function of lung graft via regulating pulmonary surfactant stability and decreased the lung graft IRI via decreasing the inflammatory response and cell apoptosis.

Dexmedetomidine Alleviates Lung Oxidative Stress Injury Induced by Ischemia-Reperfusion in Diabetic Rats via the Nrf2-Sulfiredoxin1 Pathway.

Oxidative stress injury (OSI) is an important pathological process in lung ischemia-reperfusion injury (LIRI), and diabetes mellitus (DM) can exacerbate this injury. Dexmedetomidine protects against LIRI by reducing OSI. However, the effect of dexmedetomidine on LIRI under diabetic conditions remains unclear. Therefore, this study is aimed at exploring the effects and mechanisms of dexmedetomidine on OSI induced by LIRI in diabetic rats. Rats were randomly divided into control+sham (CS), DM+sham (DS), control+ischemia-reperfusion (CIR), DM+ischemia-reperfusion (DIR), and DM+ischemia-reperfusion+dexmedetomidine (DIRD) groups (n = 6). In the CS and DS groups, the nondiabetic and diabetic rats underwent thoracotomy only without LIRI. In the CIR, DIR, and DIRD groups, LIRI was induced through left hilum occlusion for 60 min, followed by reperfusion for 120 min in nondiabetic and diabetic rats, and rats in the DIRD group were administered dexmedetomidine (3, 5, and 10 µg/kg). Compared with those in the CS group, the OSI, lung compliance, apoptosis, and oxygenation indices deteriorated in the DS group (P < 0.05), and these indices were further aggravated in the CIR and DIR groups (P < 0.05), being the worst in the DIR group (P < 0.05). Compared to those of the DIR group, the OSI, lung compliance (15.8 ± 2.4 vs. 11.6 ± 1.7 ml/kg), apoptosis (22.5 ± 2.6 vs. 51.8 ± 5.7), oxygenation (381 ± 58 vs. 308 ± 78 mmHg), and caspase-3 and caspase-9 protein expression indices were attenuated, and Nrf2 and sulfiredoxin1 protein expression was increased in the DIRD group (P < 0.05). And the lung injury, oxygenation, OSI, and Nrf2 and sulfiredoxin1 protein expression changed in a concentration-dependent manner. In conclusion, dexmedetomidine alleviated lung OSI and improved lung function in a diabetic rat LIRI model through the Nrf2-sulfiredoxin1 pathway.

Methane Inhalation Protects Against Lung Ischemia-Reperfusion Injury in Rats by Regulating Pulmonary Surfactant via the Nrf2 Pathway.

Methane (CH4) exerted protective effects against lung ischemia-reperfusion (I/R) injury, but the mechanism remains unclear, especially the role of pulmonary surfactant. Therefore, this study aimed to explore the effects of CH4 inhalation on pulmonary surfactant in rat lung I/R injury and to elucidate the mechanism. Rats were randomly divided into three groups (n = 6): the sham, I/R control, and I/R CH4 groups. In the sham group, only thoracotomy was performed on the rats. In the I/R control and I/R CH4 groups, the rats underwent left hilum occlusion for 90 min, followed by reperfusion for 180 min and ventilation with O2 or 2.5% CH4, respectively. Compared with those of the sham group, the levels of large surfactant aggregates (LAs) in pulmonary surfactant, lung compliance, oxygenation decreased, the small surfactant aggregates (SAs), inflammatory response, oxidative stress injury, and cell apoptosis increased in the control group (P < 0.05). Compared to the control treatment, CH4 increased LA (0.42 ± 0.06 vs. 0.31 ± 0.09 mg/kg), oxygenation (201 ± 11 vs. 151 ± 14 mmHg), and lung compliance (16.8 ± 1.0 vs. 11.5 ± 1.3 ml/kg), as well as total antioxidant capacity and Nrf2 protein expression and decreased the inflammatory response and number of apoptotic cells (P < 0.05). In conclusion, CH4 inhalation decreased oxidative stress injury, inflammatory response, and cell apoptosis, and improved lung function through Nrf2-mediated pulmonary surfactant regulation in rat lung I/R injury.

Efficacy of silver needle therapy for the treatment of chronic nonspecific low back pain: a prospective, single-center, randomized, parallel-controlled clinical trial.

BACKGROUND: Chronic nonspecific low back pain (CNSLBP) troubles approximately 30% of people worldwide. Silver needle therapy (SNT) is a treatment method to relieve soft tissue pain through heating. Therefore, this study aimed to observe the effects of SNT on CNSLBP. METHODS: In this study, 100 patients were randomly divided into 2 groups: silver needle (SN) group and control group (n = 50). In the SN group, patients received SNT and physiotherapy, while patients received physiotherapy alone in the control group. At the 6-month follow-up, the numerical rating scale (NRS), Oswestry Disability Index (ODI), Short-Form 12 of quality of life (SF-12), the natural logarithms of low-frequency measurement (InLF), and the natural logarithms of high-frequency measurement (InHF) of heart rate variability (HRV) were recorded. RESULTS: In both groups, NRS, ODI, SF-12 scores, and HRV at 2 weeks after treatment were improved and maintained for 6 months. Compared with the control group, more significant improvements were observed in the NRS and SF-12 scores at 1, 2, 3, and 6 months and in the ODI scores at 1 and 2 months in the SN group (P <  0.05). However, there was no significant difference between the groups in the ODI scores at 3 and 6 months. InLF and InHF in the SN group were higher than those in the control group at 3 and 6 months (P <  0.05). CONCLUSIONS: SNT relieved pain and improved quality of life and autonomic nerve activity, especially parasympathetic nerve, in patients with CNSLBP, without serious complications. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR-OOC-17013237 . Registered on November 11, 2017.

Circular RNAs as New Regulators in Gastric Cancer: Diagnosis and Cancer Therapy.

Gastric cancer (GC) is one of the most commonly diagnosed cancers that causes high mortality in the world. Although the surgery tools and chemotherapies have significantly improved the overall survival of patients with GC, the early diagnosis of GC remains insufficient and many patients diagnosed with advanced stages of GC are not able to benefit from curative therapy. Circular RNAs (circRNAs), novel members of the non-coding cancer genome, are being explored with regards to various cancer types including GC. CircRNAs could work as miRNA sponges to regulate cell proliferation, cell migration, and cell cycle in GC. In addition, it was found that abnormal expression of circRNAs was associated with pathological characteristics in GC tissues, which could help to act as potential markers of early diagnosis or predictors of prognosis. Although various functional circRNAs have been discovered and characterized, the studies of circRNAs in GC are still at early stages compared with other RNAs. In order to provide a whole view to better understand the circRNAs in the occurrence and development of GC, we review the current knowledge on circRNAs in relation to their expression and regulation in GC as well as their potential to be diagnosis markers, and their role in drug resistance will be mentioned. It is helpful to address their possibility from basic research into practical application.

Application of a modified optical fiber in targeted percutaneous laser disc decompression of lumbar disc herniation: A retrospective study.

Targeted percutaneous laser disc decompression (T-PLDD) is a minimally invasive technique for the treatment of lumbar disc herniation (LDH). However, the amount of energy required is large and the nerve can be easily damaged. Therefore, this technology requires improvement. The present study aimed to observe the effects of using a modified optical fiber (Mod) in T-PLDD for the treatment of LDH. A retrospective study was conducted using the database of the Affiliated Hospital of Qingdao University (Qingdao, China). In total, 58 patients who received T-PLDD with the Mod between June 2011 and May 2012 were included in the present study. The 10-point numeric rating score, pain rating index and good-to-excellent rating at 3 months (1.64±0.97; 5.79±1.57; 94.8%) were lower than those at 1 week (5.12±1.37; 11.52±1.85; 74.2%), and at 1 month (3.26±1.41; 7.83±1.31; 82.8%; P<0.05) and were maintained for up to 36 months (1.48±0.86; 4.91±1.43; 96.5%). The Oswestry disability index and 12-item Short Form Health Survey at 6 months (24.56±6.78; 69.40±5.08) were improved compared with 1 week, 1 month and 3 months, and were maintained for 36 months (23.10±6.20; 70.89±5.39). The T2 value decreased at 1 week (76±8) and returned to normal at 3 months (152±11). Additionally, patients in the Young group (<50 years old) recovered in a shorter period of time than the patients in the Elderly group. In conclusion, the patients stayed in hospital for 3.34±0.66 days; pain decreased and function increased optimally at 3-6 months and was maintained for 36 months with no serious complications. Individuals <50 years old may be more suitable candidates for T-PLDD with the Mod. The Mod should be applied and promoted in T-PLDD, and its use should be considered in the clinical setting.

Effects of flurbiprofen on serum level of interleukin-6, prostacyclin and corticosteroid A2 in patients with bone metastases of cancer.

The present study aimed to investigate the effects of flurbiprofen on serum level of interleukin-6 (IL-6), prostacyclin (PGI2) and corticosteroid A2 (TXA2) in patients with bone metastases of cancer. A total of 210 patients with bone metastasis of cancer were randomly divided into two groups: Flurbiprofen axetil analgesia group (group A) and dezocine analgesia group (group B), 105 cases in each group. The analgesic effect was evaluated using visual analogue scale (VAS) scoring system at 1, 12, 24 and 48 h after treatment. Serum levels of IL-6, PGI2 and TXA2 at 12 and 24 h after treatment were detected using double-antibody sandwich enzyme-linked immunosorbent assay. No significant differences in VAS scores were found between the two groups at 1, 12, 24 and 48 h after treatment, and no gastrointestinal adverse events and abnormal bleeding were observed. No significant differences in the serum levels of IL-6 were found between the two groups at 12 and 24 h after treatment. Significantly lower serum levels of TXA2 and PGI2 were found in group A compared to group B at 12 and 24 h after treatment (P<0.05). Serum level of PGI2 was positively correlated with serum level of TXA2 (r=0.7212, P<0.05) and VAS score (r=0.7159, P<0.05). Serum level of IL-6 was positively correlated with VAS score (r=0.7997, P<0.05). The results show that flurbiprofen axetil can effectively relieve pain in patients with bone metastases of cancer, can inhibit platelet activation, adhesion and aggregation, and reduce the formation of deep vein thrombosis, and can inhibit stress response and inflammatory response in the body.

Astragaloside attenuates myocardial injury in a rat model of acute myocardial infarction by upregulating hypoxia inducible factor­1α and Notch1/Jagged1 signaling.

The present study aimed to investigate the mechanisms underlying the cardioprotective effect of Astragaloside against myocardial injury following myocardial infarction (MI) in a rat model. Male Wistar rats were subjected to left anterior descending branch ligation. The rats that survived 24 h (n=18) were randomly and equally assigned to three groups: MI model group, and 2.5 and 10 mg/kg/day Astragaloside group. A further six rats underwent identical surgical procedures without artery ligation, serving as sham controls. Following 28 days of treatment, the left ventricle was harvested for morphological analysis, and mRNA and protein expression levels of hypoxia inducible factor­1α (HIF­1α), Notch1 and Jagged1 were measured. Treatment with Astragaloside attenuated pathological changes in the myocardium. Compared with untreated MI rats, rats treated with Astragaloside exhibited significantly increased mRNA expression levels of HIF­1α, Notch1 and Jagged1 (all P<0.01). HIF­1α demonstrated a dose­dependent effect (P<0.05). Astragaloside (10 mg/kg/day) significantly increased HIF­1α (P<0.05), Notch1 (P<0.01) and Jagged1 (P<0.01) protein expression levels. Additionally, 2.5 mg/kg Astragaloside significantly increased Jagged1 protein expression levels compared with untreated MI rats. Furthermore, there was a dose­dependent effect of Astragaloside treatment (P<0.01). These findings suggested that the cardioprotective effects of Astragaloside against myocardial injury following MI may involve upregulation of HIF­α, Notch1 and Jagged1 signaling, implicating these molecules as therapeutic targets for the treatment of MI.

Structure-based rational design of self-inhibitory peptides to disrupt the intermolecular interaction between the troponin subunits C and I in neuropathic pain.

The troponin (Tn) is a ternary complex consisting of three subunits TnC, TnI and TnT; molecular disruption of the Tn complex has been recognized as an attractive strategy against neuropathic pain. Here, a self-inhibitory peptide is stripped from the switch region of TnI interaction interface with TnC, which is considered as a lead molecular entity and then used to generate potential peptide disruptors of TnC-TnI interaction based on a rational molecular design protocol. The region is a helical peptide segment capped by N- and C-terminal disorders. Molecular dynamics simulation and binding free energy analysis suggests that the switch peptide can interact with TnC in a structurally and energetically independent manner. Terminal truncation of the peptide results in a number of potent TnC binders with considerably simplified structure and moderately decreased activity relative to the native switch. We also employ fluorescence polarization assays to substantiate the computational findings; it is found that the rationally designed peptides exhibit moderate or high affinity to TnC with dissociation constants KD at micromolar level.

Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction.

The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Twenty­four hours after surgery, the rats were divided into low­dose, high­dose, control and sham surgery groups (n=8 per group). The low­ and high­dose groups were treated with ASTs (2.5 and 10 mg/kg/day, respectively, via intraperitoneal injection), while, the control and sham surgery group rats received saline. Serum levels, and mRNA and protein expression levels of VEGF and bFGF, as well as the microvessel density (MVD) were determined four weeks post­treatment. Twenty­four hours post­surgery, VEGF and bFGF serum levels were observed to be comparable between the groups; while at four weeks, the VEGF and bFGF levels were higher in the AST­treated rats (P<0.01). Similarly, VEGF and bFGF mRNA and protein expression levels were higher following AST treatment (P<0.05). No difference in VEGF mRNA expression between the low­ and high­dose groups was noted, however, an increase in the bFGF expression levels was detected in the high­dose group. Newly generated blood vessels were observed following MI, with a significant increase in MVD observed in the AST­treated groups (P<0.05). AST promotes angiogenesis of the heart and increases VEGF and bFGF expression levels. Thus, it is hypothesized that increased VEGF and bFGF levels may contribute to the AST­induced increase in angiogenesis in rat models of MI.

Correlations of O3 therapeutic targets and imaging localization in lumbar intervertebral disc protrusion.

OBJECTIVE: This study aims to investigate correlations between the effects of O3 target-injection treatment and imaging localization in lumbar intervertebral disc protrusion (LIDP). METHODS: 164 LIDP patients were divided into 3 groups: group A, the protrusion located at level I-III, region 1-2, domain a-b; group B, the protrusion located at level I-III, region 1-2, domain c-d; group C: the protrusion located at level I-III, region 3-4, domain a-b. The patients were treated with LIDP O3-target treatment + blocking therapy with epidural anti-inflammatory analgesic liquid. RESULTS: Among the 164 LIDP patients, 95 patients (57.93%) exhibited the significant effectiveness after the treatment; 64 cases (39.02%) exhibited the effectiveness. The results of functional improvements revealed that 50 cases (53.76%) of sagittal plane and 54 cases of horizontal plane (55.67%) in the group A, 33 cases (35.48%) and 31 cases (31.96%) in the group C respectively were significantly better than those in the group B (10 cases, 10.75%; 12 cases, 12.37%) (P < 0.05). The visual analogue scale (VAS) scores 1 week and 1 month after the treatment in the three groups were significantly decreased than those before the treatment (P < 0.05). The intergroup comparison revealed that the A group (1 week 2.28 ± 0.85, 1 month 1.21 ± 0.27) and C (2.79 ± 0.98, 1.38 ± 0.55) were significantly better than the B group (3.92 ± 1.14, 2.53 ± 0.51) (P < 0.05). CONCLUSIONS: The O3 target-injection treatment exhibited the best effects in treating the LIDP patients with the protrusion located at level I-III, region 1-2, domain a-b.

CGRP 4218T/C polymorphism correlated with postoperative analgesic effect of fentanyl.

PURPOSE: Our study aimed at evaluating the association between α-calcitonin gene-related peptide (CGRP) 4218T/C polymorphism and the patient-controlled analgesic (PCA) effect of fentanyl on Chinese Han population. METHODS: 98 patients were involved in the experiment, but only 92 patients completed the experiment. 0.1 mg/kg fentanyl was given to the patients through intravenous injection ten minutes before the ending of surgery. The patients achieved PCA by controlling the fentanyl infusion pump and a single dose was 1 mg. The CGRP 4218T/C polymorphism was genotyped with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The fentanyl consumption within the 72 hours after the surgery was recorded and the pain was assessed with numeric rating scale (NRS) method. RESULTS: The patients were divided into three groups of wild homozygote (T/T), heterozygote (T/C), and mutant homozygote (C/C). At the 6th hour and the 12th hour after the surgery, the fentanyl consumption for PCA of the T/C group was significantly higher than the T/T group (P<0.05). Meanwhile, the fentanyl consumption of the C/C group was much higher than the T/T group (P<0.05) at the 12th hour and the 24th hour. Besides, the fentanyl consumption of the C/C group was more than the T/C group (P<0.05) at the 24th hour. The differences in NRS scores, Ramsey scores, and postoperative adverse reactions between each group at all time points were not statistically significant. CONCLUSIONS: CGRP 4218T/C polymorphism may be associated with the postoperative fentanyl consumption for analgesia.

Combined effects of irbesartan and carvedilol on expression of tissue factor and tissue factor pathway inhibitor in rats after myocardial infarction.

The objective of this study was to investigate the effects of irbesartan, carvedilol, and irbesartan plus carvedilol on the expression of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) mRNA and protein in rat myocardium after myocardial infarction (MI). MI was induced in male Wistar rats by ligation of the anterior descending branch of the left coronary artery. Irbesartan at 50 mg/kg/day, carvedilol at 1 mg/kg/day, irbesartan plus carvedilol, or placebo was administered intragastrically; expression of TF and TFPI mRNA and protein was determined by RT-PCR and Western blot analysis. The relative left ventricle weights were lower in all three treatment groups than in the placebo group, with the lowest relative weight in the irbesartan plus carvedilol group (P < 0.001). The size of the infarcted area was lower in the carvedilol and the combined groups than in the placebo group (P < 0.001). The levels of expression of TF and TFPI mRNA and protein were lower in the combined group than in the placebo group or the carvedilol group (P < 0.001). Treatment with irbesartan plus carvedilol reduced the expression of TF and TFPI mRNA and protein after MI in rats, and combined treatment with both agents had greater effects than the single agents alone. These findings suggest that the beneficial effects of these drugs may include anticoagulation and that combined therapy with both agents is an option that should be evaluated further.