The effects of manual therapy in pain and safety of patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Manual therapy (MT) is frequently used in combination with management of osteoarthritis of the knee, but there is no consensus on the exact efficacy of this treatment strategy. The purpose of this systematic review and meta-analysis was to evaluate the pain relief and safety of MT for treatment of knee osteoarthritis (KOA). METHODS: Randomized controlled trials evaluating MT in patients with KOA in major English and Chinese journals were searched in the following databases: Wanfang, China Science and Technology Journal Database (VIP database), China National Knowledge Infrastructure (CNKI), PubMed, Embase, Web of Science, and the Cochrane Library databases through June 2023. The methodological quality and quality of evidence of the included studies were assessed using Cochrane's risk-of-bias 2 (ROB 2) tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Data analysis was performed using Stata version 15.0 software. After use of Galbraith plots to exclude studies that could lead to heterogeneity, random effects models were used to analyze the remaining data and test the consistency of the findings. We used meta-regression to assess the effect of treatment period, patient age, and sex ratio on outcomes. Funnel plots and Egger's test were used to evaluate publication bias. Sensitivity analyses were used to determine the reliability of the results. RESULTS: A total of 25 studies, with 2376 participants, were included in this review. The overall methodological quality of the included studies was limited. Our findings suggest that MT has a positive impact on pain relief outcomes in KOA patients. The meta-analysis showed that MT was superior to usual care (SMD = 2.04, 95% CI 0.94, 3.14, I 2 = 96.3%; low evidence quality) and exercise (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%; low evidence quality) for reducing pain. In terms of improvement in visual analogue scale (VAS) scores, MT treatment beyond 4 weeks (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%) may be superior to treatments less than or equal to 4 weeks (SMD = 1.24, 95% CI 0.56, 1.95, I 2 = 94.7%). No serious adverse events associated with MT were reported. CONCLUSIONS: MT may be effective at reducing pain in patients with KOA and may be more effective after a 4-week treatment period. Compared with usual care and exercise therapy, MT may be superior at reducing KOA pain in the short term (9 weeks), but its long-term efficacy requires careful consideration of evidence-based outcomes. MT appears to be safe for KOA patients, though clinicians should inform patients of the potential risk of MT-related adverse events.

Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis.

Background: Although immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatment for resected melanoma, the optimal therapy remains controversial. Therefore, we conducted this updated network meta-analysis (NMA) to assess the efficacy and tolerability of adjuvant therapies for cutaneous melanoma. Methods: PubMed, Embase, Cochrane library, and Web of Science were systematically searched for relevant literatures published in the last 30 years. Disease-free survival (DFS), overall survival (OS), and serious adverse events were considered as the efficacy and tolerability outcomes. Results: In all, 27 randomized controlled trials (RCTs) including 16,709 stage III-IV melanoma patients were enrolled in this NMA. For BRAF wild-type melanoma, our analysis showed that both nivolumab and pembrolizumab demonstrated significantly better DFS and tolerability than ipilimumab (10 mg/kg). Nivolumab, pembrolizumab, ipilimumab (3 mg/kg), and ipilimumab (10 mg/kg) all appeared to be effective in prolonging OS, but no therapy demonstrated significantly better OS than ipilimumab (10 mg/kg). Nivolumab + ipilimumab showed the best DFS, but did not appear to be effective in improving OS and ranked only seventh in tolerability. Vaccines and granulocyte-macrophage colony-stimulating factor therapies were well tolerated, but all failed to improve the DFS or OS in stage III melanoma patients. In terms of BRAF mutation-positive melanoma, ICIs (nivolumab + ipilimumab, nivolumab, pembrolizumab, ipilimumab; 10 mg/kg) exhibited comparable efficacy to dabrafenib + trametinib, and all these therapies showed significantly better DFS than placebo. Conclusion: Considering efficacy and tolerability, nivolumab and pembrolizumab seem to be preferable adjuvant therapies for patients with stage III-IV melanoma. For BRAF mutation-positive patients, more RCTs are still required to determine which is better between ICIs and targeted therapy.

Helicobacter pylori infection and PD-L1 expression in gastric cancer: A meta-analysis.

BACKGROUND: High expression of programmed death ligand-1 (PD-L1) has been related to good response to immunotherapy patients with gastric cancer (GC). However, the influence of Helicobacter pylori (HP) infection on PD-L1 expression in GC remains unknown. A meta-analysis was performed to evaluate the association between HP infection and PD-L1 expression in GC. METHODS: Observational studies that investigated the relationship between HP infection and PD-L1 expression in patients with GC were obtained by search electronic databases, including PubMed, Embase, Cochrane's Library and Web of Science. A random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results. RESULTS: Ten studies with 1870 patients with GC contributed to the meta-analysis. Pooled results showed that HP infection was significantly associated with the tumour expression of PD-L1 (odds ratio [OR]: 1.90, 95% confidence interval: 1.33-2.72, p < .001; I2  = 53%). Subgroup analyses showed that the association between HP infection and PD-L1 expression in GC was not significantly affected by sample size, methods for PD-L1 evaluation and quality score (p for subgroup analyses all >.05). However, a stronger association was observed in studies with higher prevalence of HP infection (≥35%, OR: 2.58) as compared with those with lower prevalence (<35%, OR: 1.45, p for subgroup difference = .04). CONCLUSION: Helicobacter pylori infection in GC patients is associated with tumour expression of PD-L1, suggesting HP infection may be a predictor of good response to immunotherapy in GC.

The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. Therefore, the purpose of this meta-analysis was to evaluate the efficacy of programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) inhibitors versus that of standard-of-care therapy in patients with NSCLC who were bTMB high and bTMB low. METHODS: PubMed, Embase, Cochrane, the Web of Science, and ClinicalTrials.gov were searched systematically from inception to February 2021 for studies of PD-1/PD-L1 inhibitors (durvalumab OR atezolizumab OR avelumab OR pembrolizumab OR Nivolumab) that provided hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS), or odds ratios (ORs) for objective response rate (ORR) in both bTMB high and bTMB low groups. RESULTS: A total of 2338 patients with advanced or metastatic NSCLC from six randomized controlled trials, which all used chemotherapy (CT) as a control, were included in this study. Compared with CT, PD-1/PD-L1 inhibitor therapy improved OS (HR 0.62, 95% CI 0.52-0.75, P < 0.01), PFS (HR 0.57, 95% CI 0.48-0.67, P < 0.01), and ORR (OR 2.69, 95% CI 1.84-3.93, P < 0.01) in bTMB-high NSCLC patients but not in bTMB-low patients (OS HR 0.86, 95% CI 0.69-1.07, P = 0.17; PFS HR 1.00, 95% CI 0.78-1.27, P = 0.98; ORR OR 0.63, 95% CI 0.49-0.80, P = 0.03). Subgroup analyses showed that these results were consistent across all subgroups (line of therapy, therapy regimen, type of NGS panel, PD-L1 expression, and cutoff value). Meta-regression analysis showed that the proportion of patients with squamous cell histology had no statistical effect on clinical outcomes. Sensitivity analyses illustrated that all results were stable. CONCLUSIONS: The efficacy of PD-1/PD-L1 inhibitor therapy in advanced NSCLC patients may be dependent on bTMB level. Patients with high bTMB tend to obtain significantly better OS, PFS, and ORR from PD-1/PD-L1 inhibitor therapy than from CT. However, because of multiple limitations, including those related to reproducibility, the results are exploratory and should be interpreted with caution.

Celastrus orbiculatus Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H.

BACKGROUND: Celastrus orbiculatus ethyl acetate extract (COE) has shown a strong anti-gastric cancer effect, but the understanding of its mechanism is still lacking. The results of previous studies indicated that COE may be able to inhibit the stemness of gastric cancer stem cells (GCSCs) by regulating PDCD4 and EIF3H expression. AIMS: To explore if COE could inhibit the stemness of GCSCs by regulating PDCD4 and EIF3H expression in vitro and in vivo. PROCEDURE: The GCSCs model was established by stem cell-conditioned culture. Spheroid formation and flow cytometry assays were used to detect the effect of COE on the spheroid formation ability of GCSCs and the percentage of CD44+/CD24+ and ALDH+ cell subpopulations. Western blot analysis was applied to measure the expression of GCSCs biomarkers (Nanog, Oct-4, and SOX-2), PDCD4, and EIF3H in GCSCs treated with COE; and RT-PCR was performed to investigate the effect of COE on PDCD4 mRNA expression in GCSCs. An in vivo tumorigenicity experiment was also conducted to evaluate the effect of COE on tumor-initiating ability of GCSCs in vivo; and the expression of PDCD4 and EIF3H in xenograft tissues was examined by immunohistochemistry (IHC) staining. RESULTS: After culture in stem cell-conditioned medium, SGC7901 cells manifested significantly enhanced spheroid formation ability, upregulated Nanog, Oct-4, and SOX-2 expression and increased percentages of CD44+/CD24+ and ALDH+ cell subpopulations, indicating successful establishment of the GCSCs model. COE treatment significantly inhibited the spheroid formation ability of GCSCs and reduced the percentage of CD44+/CD24+ and ALDH+ cell subpopulations. The western blot analysis showed a significant decrease of Nanog, Oct-4, SOX-2, and EIF3H expression and an increase of PDCD4 expression in GCSCs after COE treatment in a concentration-dependent manner. COE treatment also significantly upregulated the mRNA expression of PDCD4 in GCSCs. In addition, COE displayed a strong inhibitory effect on the tumor-initiating ability of GCSCs in vivo and upregulated PDCD4 and downregulated EIF3H expression in xenograft tissues. CONCLUSION: COE may be able to inhibit GC growth by suppressing the stemness of GCSCs via regulating PDCD4 and EIF3H expression.

[Assessing water sources for Populus simonii with different degrees of degradation based on stable isotopes].

Water availability is the key factor limiting plant growth in arid regions. Populus simonii is a typical shelterbelt tree species in Zhangbei County, Hebei Province, with an important role in constructing ecological barrier. With stable isotope technique, graphical method, and multiple linear mixing model, we analyzed water sources and water use strategies of P. simonii in different growth periods with four different degrees of degradation (non-degraded, slightly degraded, modera-tely degraded and severely degraded) in Zhangbei County. Results would help improve our understanding on the cause and mechanism of the large-scale degradation of P. simonii in this area. The results showed that water sources of P. simonii in the early growth stage (May-June) from all four degradation degrees were relatively simple. P. simonii mainly used soil water in 0-40 cm, with the utilization rates being 34.2%, 50.1%, 41.6%, and 55.7% for the four degradation degrees, respectively. At the middle growth stage (July-August), non-degraded P. simonii utilized soil water from layers of 200-280 cm and 280-400 cm, with utilization rates of 20.2% and 30.9%, respectively. Soil water at 200-280 cm and 280-400 cm layers was utilized by slightly degraded poplar, with the contribution rates of each layer being 33.2% and 27.9%, respectively. Moderately degraded P. simonii utilized soil water from the depths of 0-40 cm and 40-120 cm, with the rates of 30% and 26.9%, respectively. Water utilization rate of severely degraded P. simonii to 0-40 cm depth was 55.4%. At the late growth stage (September-October), water sources of non-degraded P. simonii transferred to the upper-middle soil layers, with the utilization rate of 0-40 cm, 40-80 cm, and 80-120 cm being 23.3%, 17.2%, and 16.5%, respectively. The utilization rate of the slightly degraded P. simonii was 35.7% at 0-40 cm and 20.6% at 80-200 cm. The moderately and severely degraded P. simonii mainly utilized soil water at 0-40 cm layer, with the contribution rates of soil water being 43.7% and 51.8%, respectively. With the exacerbation of degradation, the main water source of P. simonii gradually transferred from deep to surface soil water.

Clinical analysis of arytenoid cartilage reposition with snake mouth forceps for the arytenoid cartilage dislocation / 临床耳鼻咽喉头颈外科杂志

OBJECTIVES@#To investigate the clinical effect of the arytenoid cartilage reposition using snake mouth reduction forceps under general anesthesia.@*METHODS@#Data of twenty-six cases accepted arytenoid cartilage reposition under intravenous general anesthesia were analyzed, nineteen cases accepted laryngeal CT scan and cricoarytenoid joint reconstruction, all patients underwent endolaryngeal muscle electromyography examination. According to the position of cartilage dislocation prompted by laryngoscope and CT, the arytenoid cartilage was repositoned under the visual laryngoscope using special snake mouth reduction forceps. If bilateral arytenoid cartilage were still asymmetrically at the end of the surgery, patients needed repeated reposition 1 to 2 times 1 week after operation. The efficacy was evaluated 4 weeks later.@*RESULTS@#All patients had a hoarse and breathing voice preoperative. Under laryngoscope, there were different degrees of vocal cord movement disorders accompanied by incomplete glottis closure, 22 cases happened in left side and 4 in right side. The arytenoid cartilage was dislocated anteromedially in 25 cases and posterolaterally in 1 case. CT showed that 15 cases of arytenoid cartilage were tilted anteromedially; the interval of the cricoarytenoid joint was widened. In axial CT images, there were no direct signs of the arytenoid cartilage dislocation in the 4 cases, but the abnormal position was seen in the reconstruction images. The laryngeal electromyography indicated that 7 cases were abnormal, duration of motor unit potential were visible and the raising potential were mixed. There were 4 patients with normal voice in the first day after surgery, and 19 cases underwent twice and 3 cases underwent three times surgery. Vioce became normal in 4 weeks. Swallowing pain and bucking were all disappeared. Vocal cords movement were recovered to normal level in 25 cases. In 1 case with neck strangulation, the vocal cord movement was slightly worse than health side, but significantly better than that before operation.@*CONCLUSIONS@#The arytenoid cartilage reposition using snake mouth reduction forceps under general anesthesia was an effective method for the treatment of the cricoary-tenoid joint dislocation.