Nanomaterials: Recent Advances in Knee Osteoarthritis Treatment.

Osteoarthritis (OA) of the knee is the most prevalent degenerative joint condition that places a substantial financial and medical burden on society. However, due to drawbacks such as inefficiency, adverse effects, and brief duration of action, the clinical efficacy of the current major therapies for knee OA is largely restricted. Therefore, novel medication development is highly required to address these issues. Numerous studies in recent years have established that nanomaterials can be a potential and highly effective way to overcome these challenges. In this review, the anatomical distinctions between healthy and OA knee joints, as well as novel advances in the field of nanomaterials for the treatment of knee OA are summarized. The limits of the present therapeutic strategies for treating knee OA are also highlighted, as well as the potential prospects of nanomaterials in the future.

Prognostic predictive modeling of non-small cell lung cancer associated with cadmium-related pathogenic genes.

Persistent exposure to low-dose of cadmium is strongly linked to both the development and prognosis of non-small cell lung cancer (NSCLC), yet the precise molecular mechanism behind this relationship remains uncertain. In this study, cadmium-related pathogenic genes (CRPGs) in NSCLC were identified via differential expression analysis. NSCLC patient clusters related to CRPGs were constructed through univariate Cox and K-means clustering algorithms. Multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were employed to determine the prognosis. Sixteen CRPGs showed a significant association with NSCLC. We found biological and prognostic differences between patients in clusters A and B. A predictive prognostic risk model for NSCLC revealed that FAM83H, MSMO1, and SNAI1 are central. Hence, the 3 hub genes were named. To further elucidate the role of CRPGs in NSCLC, A549 cells were exposed to CdCl2. The mRNA and protein expression levels of the 3 hub genes and cell invasion were detected. Moreover, 10 µM CdCl2 may increase the protein expression of 3 hub genes and enhance the invasive ability of A549 cells. This risk model may have established a theoretical foundation for investigating the mechanisms, treatment, and prognosis of NSCLC.

Associations of sleep disorders with all-cause and cause-specific mortality in cancer survivors: a cross-sectional analysis of the NHANES 2005-2016.

BACKGROUND: The circadian clock and endoplasmic reticulum stress signaling play important roles in oncogenesis and development of cancer. Sleep disorders have been linked to an elevated risk of mortality in general populations. Nonetheless, the evidence for the sleep disorders-mortality association among cancer patients is limited. We aimed to prospectively investigate the association of sleep disorders with all-cause, cancer, and cardiovascular disease (CVD) mortality among cancer individuals. METHODS: We assessed 3187 participants with cancer from the National Health and Nutrition Examination Survey 2005-2016 cohorts with a median follow-up time of 83.0 months. Multivariable Cox proportional hazards models estimated the adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Multivariable Cox proportional hazards models showed that sleep disorders were associated with a higher risk of all-cause mortality (HR 1.23, 95%CI: 1.06,1.42), cancer mortality (HR 1.30, 95%CI: 1.02, 1.66), and cardiovascular disease mortality (HR 1.35, 95%CI: 1.02, 1.80). After the total group was stratified by gender, the high HRs were observed in men (P < 0.05), not in women. The correlation between sleep disorders and higher long-term mortality was also significant after individuals who died within 2 years of follow-up were excluded, with HR 1.24 (95%CI: 1.07, 1.45) in model I, HR 1.20 (95%CI: 1.02, 1.42) in model II for long-term all-cause mortality, HR (95%CI: 1.00, 1.74) in model I for long-term cancer mortality, and HR 1.5 (95%CI:1.12, 2.02) in model I, HR 1.45 (95%CI: 1.06, 1.99) in model II for long-term CVD mortality. CONCLUSIONS: Sleep disorders were associated with a higher risk of all-cause mortality, cancer mortality, and CVD mortality, as well as long-term mortality in cancer patients. Our finding underlies the importance of screening for sleep disorders for all cancer survivors and the urge to integrate sleep health as an important part of cancer care more effectively. Male individuals may be particularly vulnerable and could benefit from more frequent screening.

Predictive value of systemic immune-inflammation index in the high-grade subtypes components of small-sized lung adenocarcinoma.

BACKGROUND: Identification of micropapillary and solid subtypes components in small-sized (≤ 2 cm) lung adenocarcinoma plays a crucial role in determining optimal surgical procedures. This study aims to propose a straightforward prediction method utilizing preoperative available indicators. METHODS: From January 2019 to July 2022, 341 consecutive patients with small-sized lung adenocarcinoma who underwent curative resection in thoracic surgery department of Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The patients were divided into two groups based on whether solid or micropapillary components ≥ 5% or not (S/MP5+ and S/MP5-). Univariate analysis and multivariate logistic regression analysis were utilized to identify independent predictors of S/MP5+. Then a nomogram was constructed to intuitively show the results. Finally, the calibration curve with a 1000 bootstrap resampling and the receiver operating characteristic (ROC) curve were depicted to evaluate its performance. RESULTS: According to postoperative pathological results, 79 (23.2%) patients were confirmed as S/MP5+ while 262 (76.8%) patients were S/MP5-. Based on multivariate analysis, maximum diameter (p = 0.010), consolidation tumor ratio (CTR) (p < 0.001) and systemic immune-inflammation index (SII) (p < 0.001) were identified as three independent risk factors and incorporated into the nomogram. The calibration curve showed good concordance between the predicted and actual probability of S/MP5+. Besides, the model showed certain discrimination, with an area under ROC curve of 0.893. CONCLUSIONS: The model constructed based on SII is a practical tool to predict high-grade subtypes components of small-sized lung adenocarcinoma preoperatively and contribute to determine the optimal surgical approach.

Ultrasound-guided anterior quadratus lumborum block at the L2 level for postsurgical analgesia in patients undergoing laparoscopic gynaecological surgery: a single-centre, randomised, double-blinded trial at a university-affiliated hospital in China.

OBJECTIVE: This study aimed to investigate the analgesic effect of an ultrasound-guided anterior quadratus lumborum block (QLB) at the L2 level on postoperative pain after laparoscopic gynaecological surgery. DESIGN: Prospective single-centre randomised double-blind trial. SETTING: University-affiliated hospital. PARTICIPANTS: Sixty patients aged between 18 and 65 years scheduled for laparoscopic gynaecological surgery. INTERVENTIONS: Before surgery, bilateral anterior QLB was performed with 20 mL of 0.375% ropivacaine injected on each side in the QLB group, whereas equal amount of saline was administered in the placebo group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative morphine dose in the first 24 hours, and the secondary endpoints were morphine consumption at each time interval, area under the curve (AUC) of the numeric rating scale (NRS) for pain, maximum pain intensity, incidence of moderate-to-severe pain (NRS>3), sedation score, adverse events, and time to home-readiness. RESULTS: Cumulative morphine consumption in the first 24 hours after surgery was significantly lower in the QLB group than in the placebo group (mean difference, 14.2; 95% CI 6.3 to 22.1; p<0.001). The AUCs of NRS pain intensity scores, including visceral and incisional pain at rest and on movement, were significantly lower in the QLB group than in the placebo group (all p<0.001). The time to home-readiness was significantly shorter in the QLB group than in the placebo group (p<0.05). CONCLUSION: Ultrasound-guided anterior QLB at the L2 level significantly reduced morphine consumption and relieved visceral and incision pain intensity after laparoscopic gynaecological surgery, which was beneficial for enhanced recovery. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-IOR-17011960).

[Mechanisms of moxibustion preconditioning underlying improving learning-memory ability by regulating polarization of microglia via TLR4/NF-κB signaling pathway in AD rats].

OBJECTIVE: To observe the effect of moxibustion preconditioning on learning-memory ability, Toll like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signal pathway related proteins and microglia in rats with Alzheimer's disease (AD), so as to explore its possible mechanisms underlying improvement of AD. METHODS: Male SD rats were randomly divided into normal, sham operation, AD model and pre-moxibustion groups, with 9 rats in each group. Moxibustion was applied to "Baihui"(GV20), "Shenshu"(BL23) and "Zusanli"(ST36) for 15 min, once daily, 6 days as a course of treatment for 3 courses. At the end of moxibustion, the AD model was established by injection of Aß25-35 aggregation solution into the bilateral hippocampus. The sham operation group was only injected with the same amount of 0.9% Nacl solution. The spatial learning-memory ability of rats was detected by Morris water maze test, the ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM). The histopathological changes of hippocampus tissue were observed by HE staining, and the protein expression levels of TLR4 and NF-κB p65 in the hippocampus detected by Western blot, and the positive expressions of Iba-1, CD80 and CD206 in the hippocampal CA1 region were detected by immunofluorescence labeling. The contents of inflammatory factors IL-1ß, TNF-α and IL-10 in the hippocampus were measured by ELISA. RESULTS: Compared with the sham operation group, the escape latency was significantly increased (P<0.01), and the number of platform quadrant crossing times was decreased (P<0.01) in the model group. In comparison with the model group, the increased escape latency and the decreased platform quadrant crossing times were reversed in the pre-moxibustion group (P<0.01). TEM and light microscope observation showed loose arrangement of cells, enlarged cell space, degeneration, swelling and deformation of hippocampal neurons, rupture of membranes of a large number of cells, reduction of mitochondria, dilation of endoplasmic reticulum, and matrix vacuoles, uneven distribution of organelles and cytoplasm, and being difficult in distinguishing the nuclear cytoplasm in the model group, which was relatively milder in the pre-moxibustion group. The expression levels of hippocampal NF-κB p65 and TLR4, the mean immunofluorescence density of Iba-1 and CD80, as well as the contents of IL-1ß and TNF-α in hippocampal CA1 region were significantly increased in the model group than those in the sham operation group (P<0.01), and obviously decreased in the pre-moxibustion group than those in the model group (P<0.05, P<0.01). Whereas the expression of CD206 and the content of IL-10 were evidently decreased in the model group than those in the sham operation group (P<0.01), and strikingly increased in the pre-moxibustion group than those in the model group (P<0.01). No significant differences were found between the sham operation group and the normal group in all the indexes mention above (P>0.05). CONCLUSION: Pre-moxibustion at GV20, BL23 and ST36 can improve learning-memory ability in AD rats, which may be associated with its functions in promoting the polarization of microglia from M1 to M2 and reducing the neuroinflammatory response by way of TLR4/NF-κB signaling pathway.

Cytosolic JNK-dependent microtubule reassembly protects Jurkat leukemia cells from selenite-induced apoptosis.

BACKGROUND: Selenite at high dosage exhibits great potential in curing tumors. It has been shown that selenite inhibits tumor growth through regulation of microtubule dynamics, however, the exact underlying mechanisms remained to be fully elucidated. METHODS & RESULTS: Western blots were carried out to evaluate expression level of different molecules. Our current study discovered that selenite induced microtubule disassembly, cell cycle arrest and finally resulted in apoptosis in Jurkat leukemia cells, while during this process disassembled tubulins were re-organized after long-term exposure to selenite. Furthermore, JNK was activated in the cytoplasm of selenite-treated Jurkat cells, and inhibition of JNK activity successfully prevented the process of microtubule re-assembly. Moreover, inactivation of JNK further enhanced selenite-induced cell cycle arrest and apoptosis. According to the results from cell counting-8 assay, blockage of microtubule re-assembly by colchicine further inhibited Jurkat cell viability after exposure to selenite. Experiments in a xenograft model also proved that selenite could alter JNK activity, destroy microtubule structure and inhibit cell division in vivo. Moreover, TP53, MAPT and YWHAZ were identified to be three most confident interactors that link JNK to microtubule assembly using PPIs analysis. CONCLUSION: Our study indicated that cytosolic JNK-dependent microtubule re-organization took a protective function during selenite-induced apoptosis, while inhibition of this process would finally enhance the anti-tumor effect of selenite.

Efficacy of ultrasound-guided bilateral costal margin block in laparoscopy-assisted gastrectomy: A double-blind randomized trial.

BACKGROUND: Ultrasound-guided costal margin block (CMB) is a superficial and easily applicable technique. The current study aims to investigate its analgesic efficacy in patients undergoing laparoscopy-assisted gastrectomy and describe its feasibility. METHODS: Forty-two patients undergoing laparoscopy-assisted gastrectomy were enrolled in this prospective, double-blind, randomized clinical trial. Patients were randomized to receive standard general anesthesia with (block group, n = 21) or without (control group, n = 21) ultrasound-guided bilateral CMB. The primary outcome was 24-h intravenous morphine equivalents after surgery. Secondary outcomes included consumption of titrated morphine, 24-48 h morphine equivalents, consumption of intraoperative remifentanil, numerical pain rating scale scores, time to first opioid dose, patient satisfaction, adverse effects, and recovery events. RESULTS: The postoperative 24-h morphine equivalents in the block group were significantly reduced compared to the control group (14.4 ± 7.4 mg vs. 29.9 ± 9.8 mg, p < 0.001). Both the titrated morphine consumption in the post-anesthesia care unit (PACU) and intraoperative remifentanil consumption were lower in the block group than in the control group. Patients in the block group had relatively lower average pain scores in PACU and reported more satisfaction with pain relief. Adverse effects and hospital length of stay after surgery were comparable between the two groups (p > 0.05). CONCLUSION: As a novel and easily-performed technique, ultrasound-guided bilateral CMB can reduce opioid consumption in patients undergoing laparoscopy-assisted gastrectomy.

Bibliometric Analysis Reveals the Progress of PM2.5 in Health Research, Especially in Cancer Research.

PM2.5 has an aerodynamic diameter of less than or equal to 2.5 microns due to its inherent physical and chemical properties so that it can enter the alveoli through the respiratory tract for blood gas exchange. Numerous studies have shown that PM2.5 is a serious air pollutant that poses a wide range of health risks, especially for cancer. Bibliometric methods were employed to have comprehensively analyzed the research of PM2.5 in cancer for about a decade in Web of Science to identify hotspots and trends using VOSviewer, CiteSpace, and R. The field has undergone overall growth in the past decade. As research on PM2.5 in health deepens, cancer related to it expanded beyond the respiratory system to the digestive system, urinary system, female gonadal axis, breast cancer and other cancers. Another observation is that research on PM2.5 in cancer has progressed in the mechanisms of deterioration, such as the role of matrix metalloproteinases in cancer. In addition, research on the risks of PM2.5 in combination with polycyclic aromatic hydrocarbons and heavy metals has also emerged. Results showed that there are relatively more studies on PM2.5 in high-latitude countries, which may be due to different national conditions, such as climate and coal combustion. Our research has combed through the progress of PM2.5 in cancer research and provided a supplement for developing pollution prevention ideas with different national conditions in this field.

Radiotherapy prognosis-associated gene GCNT3 promotes the proliferation, migration and invasion of lung adenocarcinoma cells.

Lung cancer is a life-threatening malignant tumour that is prevalent worldwide. Here, the GCNT3 gene in lung adenocarcinoma was studied via public databases, and cytology and molecular biology experiments were performed to further explore the role of this gene in lung adenocarcinoma. In this study, abnormally high GCNT3 expression levels were observed in tumour tissues compared with normal tissues at both the mRNA and protein levels. In the pancancer analysis, abnormal GCNT3 expression was observed in many tumour types. Moreover, the survival analysis revealed that among patients receiving radiotherapy, those with high GCNT3 expression levels had a worse prognosis. Cell and molecular biology experiments showed that the proliferation, migration and invasion capabilities of the A549 cell line were decreased after knockdown of GCNT3, and epithelial-mesenchymal transformation was significantly inhibited. In subsequent studies, we found that the sensitivity of cells to radiotherapy was enhanced after GCNT3 knockdown. Overall, our findings reveal that GCNT3 is an important factor affecting the radiotherapy sensitivity of lung adenocarcinoma, and GCNT3 inhibition deserves further study as a radiotherapy sensitising strategy.

Association between socio-economic factors and the risk of overweight and obesity among Chinese adults: a retrospective cross-sectional study from the China Health and Nutrition Survey.

BACKGROUND: With the rising prevalence of obesity and overweight, increasing number of scholars paid attention to the negative effects on human health and life. Recent years, many studies have focused on the relation of socio-economic factors with the risk of overweight or obesity, but findings have been inconsistent. This study investigated the relationship between socio-economic factors and the risk of overweight and obesity among Chinese adults. METHODS: This study was based on the survey of the China Health and Nutrition Survey in 2015, with 9245 Chinese adults aged 18-65 years old. Overweight and obesity were assessed by physical measurements of weight, height, and waist circumference. Multiple logistic models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the association. RESULTS: Overall, the prevalence rates of general obesity and abdominal obesity were 15.5% and 22.6%, respectively. We found that education and per capita household income were positively associated with overweight and obesity risk in men. However, the association between education and obesity status was negative in women [general obesity: OR = 0.64, 95% CI (0.50-0.81); abdominal obesity: OR = 0.62, 95% CI (0.51-0.76)]. Occupational status was only associated with general overweight in men. CONCLUSIONS: Results suggested that higher education and per capita household income were associated with an increased risk of overweight and obesity among Chinese men, whereas the associations were negative for women. We recommended that men with high levels of education and income, women with low levels of education, can engage in some physical activity, modify dietary, and adopt a new way of life to maintain their weight and general health.

[Involvement of miR-126-3p via mTOR/HIF-1α signaling pathway in effect of electroacupuncture on angiogenesis in rats with cerebral ischemia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on miRNA-126-3p and mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway in rats with cerebral ischemia (CI), so as to explore the underlying mechanism of EA on angiogenesis. METHODS: Male SD rats were randomly divided into control group, model group, EA group and EA+inhibitor group (inhibitor group), which were further divided into 3, 7 and 14 d subgroups, with 12 rats in each sub-group. The CI model was established by occlusion of the middle cerebral artery. EA (2 Hz/20 Hz, 0.5 mA) was applied to "Dazhui" (GV14), "Baihui" (GV20) for 20 min, once daily for 14 days at most. Rats of the inhibitor group were given an intraperitoneally injection of mTOR inhibitor (0.1 mg/mL, 0.3 mg/kg) before daily EA. The neurological function was evaluated by modified neurological severity score (mNSS). The ultrastructure of cortical neurons and microvascular endothelial cells in ischemic penumbra was observed by transmission electron microscope, and the microvessel density (MVD) of cortical endothelium in ischemic penumbra was detected by immunohistochemistry. Western blot and quantitative real-time PCR were used to detect the protein and mRNA expression of mTOR, HIF-1α and the expression of miR-126-3p in the cortex of ischemic penumbra, respectively. RESULTS: After modeling, compared with the control group at the same time point, the mNSS of the model group was increased (P<0.01), and decreased over time (P<0.01). The cortical neurons and brain microvascular endothelial cells in the ischemic penumbra were edema, and the cell structure was damaged obviously in the model group.The MVD value and the expressions of mTOR、HIF-1α proteins and mRNAs were increased (P<0.01), while the expression of miR-126-3p decreased (P<0.01) in the model group relative to the control group. Compared with the model group at the same time point, the mNSS of both intervention groups was significantly reduced (P<0.01, P<0.05), the neuron and cerebral microvascular structure improved to varying degrees, and the MVD value, the expressions of mTOR and HIF-1α protein and mRNA, and the expression of miR-126-3p of the two treatment groups were increased (P<0.01, P<0.05) at all time points (excep MVD at day 7 in the inhibitor group). Compared with the EA group at the same time point, MVD, the expressions of mTOR, HIF-1α proteins and mRNAs and miR-126-3p in the inhibitor group were all decreased (P<0.05,P<0.01). Compared with the group itself at 4 hours after modeling and day 3 and day 7, the mNSS was decreased at day 14 （P<0.01） in the model, EA and inhibitor groups. Compared with the group itself at day 3, the MVD value and the expression of mTOR protein were increased at day 7 and day 14 in the model, EA and inhibitor groups (P<0.01, P<0.05). Compared with the group itself at day 3 and day 7, the expression of mTOR mRNA and miR-126-3p were up-regulated at day 14 in the model and EA groups (P<0.01, P<0.05).Compared with the group itself at day 3, the mRNA expressions of mTOR and HIF-1α were increased at day 7 and day 14 (P<0.01, P<0.05) in the inhibitor group. CONCLUSION: EA at GV14 and GV20 can alleviate neurological deficit and improve angiogenesis in rats with CI, which may be related with its effect in up-regulating the expression of mTOR and HIF-1α, improving activation of miR-126-3p in the cortex of ischemic penumbra.

ATM/IKK alpha axis regulates the crosstalk between autophagy and apoptosis in selenite-treated Jurkat cells.

Selenium is an essential trace element. High dosage of selenite exhibits a great potential in treating leukemia. Previous study discovered selenite could promote leukemia cells apoptosis through inducing DNA damage and cell cycle arrest, while the switch mechanisms of these events and autophagy were still unclear. Current study discovered selenite promoted autophagy and apoptosis of leukemia Jurkat cells. In this process, DNA damage related ATM/IKK alpha axis was activated. This axis could stabilize pro-apoptotic P73, and promote autophagy through regulating NF-kappaB signaling pathway. Moreover, survivin-2B was also confirmed to be necessary for the ATM-induced nuclear location of IKK alpha, and therefore stood at the node position of apoptosis and autophagy cascades inside Jurkat cells. Finally, our in vivo experiments proved that selenite exhibited some anti-tumor effects on Jurkat cells-bearing mice. Moreover, alterations of ATM and IKK alpha expression observed in vivo were similar to that identified in vitro. Therefore, our findings had fully confirmed survivin-2B dependent activation of ATM/IKK alpha axis might be another crosstalk between autophagy and apoptosis of selenite-treated leukemia cells.

[Effects of pre-moxibustion on expression of phosphorylated Tau protein and related protein kinases in hippocampal CA3 region of AD rats].

OBJECTIVE: To observe the effect of pre-moxibustion at "Baihui"(GV20), "Shenshu"(BL23) and "Zusanli"(ST36) on expression of Tau protein and related protein kinases as glycogen synthase kinase-3ß (GSK-3ß), etc. in the hippocampal CA3 region of Alzheimer's disease (AD) rats, so as to explore its mechanism underlying prevention and treatment of AD cognitive impairment. METHODS: Male SD rats were randomly divided into 4 groups: normal control, sham operation， model and pre-moxibustion，with 9 rats in each group. Rats of the pre-moxibustion group received moxibustion of GV20, BL23 and ST36 for 15 min, once a day, 6 days a week for 3 weeks. After completion of moxibustion, the AD model was reproduced by injection of amyloid beta-peptide 25-35(Aß 25-35) aggregation solution 1 µL (5 µg/µL) into the bilateral hippocampus, rats of the sham operation group received injection of the same dose of normal saline into the hippocampus. The spatial learning-memory ability was detected using Morris water maze test, and changes of the ultrastructure of hippocampal neurons were observed using electron microscope, and those of histopathological changes of hippocampus tissue observed using hematoxylin eosin (H.E.) staining. The expression levels of hippocampal GSK-3ß, p-Tau, CDK5 and Synapsin I proteins were detected by Western blot and immunohistochemistry, respectively. RESULTS: No significances were found between the normal control and sham groups in all the indexes (P>0.05). Compared with the control group, the escape latency of place navigation test of Morris water maze test, expression of GSK-3ß and CDK5 and the immunoactivity of GSK-3ß, CDK5 and p-Tau were significantly increased (P<0.01), and the residence time in the platform quadrant and the number of platform crossing of spatial prob test and the expression of Synapsin Ⅰ significantly reduced in the model group (P<0.01). Following the intervention, the increase of escape latency, expression of GSK-3ß and CDK5 and the immunoactivity of GSK-3ß, CDK5 and p-Tau, and the decrease of residence time in the platform quadrant, number of platform crossing and the expression of Synapsin Ⅰ were reversed in the pre-moxibustion group (P<0.05, P<0.01). Outcomes of ultrastructure and histopathological observations respectively showed edema of hippocampal nerve cells at varying degrees, moderate edema of the cytoplasma, chromatin condensation at the edge of the nucleus, partial mitochondrial vacuole-like degeneration, fracture of tubular crest, edema and expansion of Golgi body, disappearance of polarity, fracture of the rough endoplasmic reticulum, degeneration of ribosome and partial myelin axon and reduced synaptic vesicles in the presynaptic capsule; and reduced number of neurons with shrank body, disappearance of nucleolus and blurred nuclear boundary and vacuole-like degeneration in some of them in the model group, which were relatively milder in the pre-moxibustion group. CONCLUSION: Pre-moxibustion at GV20, BL23 and ST36 plays a role in slowing down the occurrence and development of cognitive impairment in AD rats, which may be related to its functions in inhibiting tau protein hyperphosphorylation and reducing the expression of some related protein kinases in the hippocampus.

Dexmedetomidine prolongs the duration of local anesthetics when used as an adjuvant through both perineural and systemic mechanisms: a prospective randomized double-blinded trial.

BACKGROUND: To study the respective peripheral and systemic mechanisms of action of dexmedetomidine, as adjuvant to regional anesthesia, we compared dexmedetomidine added to ropivacaine for mid-forearm nerve blocks, to either systemic-only dexmedetomidine, and to a control with no dexmedetomidine. METHODS: Sixty patients undergoing hand surgery were randomly divided into three groups (n = 20 per group). Each group underwent a triple-nerve (median, radial and ulnar) mid-forearm blocks with 0.75% ropivacaine. In the DexP group, 60 µg of dexmedetomidine were added to the anesthetic mixture, while in the DexIV group, they were intravenously infused. Normal saline as a placebo was used, either as adjuvant, or intravenously. All patients underwent also a supraclavicular block with 1.5% lidocaine for tourniquet pain. The main outcomes were the duration of analgesia and the duration of sensory blockade separately for each nerve termination of the upper limb, and the duration of motor blockade of the upper limb. Tolerance was assessed by blood pressure and heart rate, and the report of adverse events. RESULTS: Duration of analgesia was longer in the DexP group, in comparison to the two other groups (P < 0.001), while it was similar in the DexIV and the control group. For cutaneous territories targeted by the three mid-forearm blocks, the between-group differences behaved similarly. For the other cutaneous territories (musculocutaneous and posterior brachial cutaneous nerves), duration of sensory blockade was shorter in the control group than in the two dexmedetomidine groups. For duration of motor blockade, the between-group differences behaved similarly. Both blood pressure and heart rate were reduced in the DexP and the DexIV groups, compared to the control. CONCLUSIONS: Dexmedetomidine used as an adjuvant to regional anesthesia may act mostly though a perineural mechanism, especially for the sensory aspects of anesthesia. A systemic action might however explain other clinical effects. TRIAL REGISTRATION: ChiCTR-IOR-17011149 , date of registration: 16/04/2017.

YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFß1-SMAD2/3 Pathway.

OBJECTIVE: YTH domain family 2 (YTHDF2) is an important N6-methyladenosine (m6A) reader, but its role in lung adenocarcinoma remains elusive. This study assessed its function in lung adenocarcinoma. METHODS: YTHDF2 expression in lung adenocarcinoma was explored using public databases, such as The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC). The effect of YTHDF2 on a lung adenocarcinoma cell line was explored by performing cytological and molecular experiments. Molecules downstream of YTHDF2 were identified using proteomics, and the related pathways were verified through cytological and molecular biology experiments. RESULTS: YTHDF2 expression was upregulated in lung adenocarcinoma, and patients with high YTHDF2 expression experienced prolonged overall survival. In two lung cancer cell lines, YTHDF2 knockdown inhibited proliferation but promoted migration, invasion, and the epithelial-mesenchymal transition. The proteomic analysis identified 142 molecules downstream of YTHDF2, and 11 were closely related to survival. Further experiments revealed that YTHDF2 inhibited expression of the family with sequence similarity 83D (FAM83D)-TGFß1-SMAD2/3 pathway components. This study is the first to show that YTHDF2 regulated the downstream TGFß1-SMAD2/3 pathway through FAM83D in lung adenocarcinoma. CONCLUSION: YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFß1-pSMAD2/3 pathway, which may play an important role in lung cancer metastasis.

Apelin-13 Reverses Bupivacaine-Induced Cardiotoxicity via the Adenosine Monophosphate-Activated Protein Kinase Pathway.

BACKGROUND: Cardiotoxicity can be induced by the commonly used amide local anesthetic, bupivacaine. Bupivacaine can inhibit protein kinase B (AKT) phosphorylation and activated adenosine monophosphate-activated protein kinase alpha (AMPKα). It can decouple mitochondrial oxidative phosphorylation and enhance reactive oxygen species (ROS) production. Apelin enhances the phosphatidylinositol 3-kinase (PI3K)/AKT and AMPK/acetyl-CoA carboxylase (ACC) pathways, promotes the complete fatty acid oxidation in the heart, and reduces the release of ROS. In this study, we examined whether exogenous (Pyr1) apelin-13 could reverse bupivacaine-induced cardiotoxicity. METHODS: We used the bupivacaine-induced inhibition model in adult male Sprague Dawley (SD) rats (n = 48) and H9c2 cardiomyocyte cell cultures to explore the role of apelin-13 in the reversal of bupivacaine cardiotoxicity, and its possible mechanism of action. AMPKα, ACC, carnitine palmitoyl transferase (CPT), PI3K, AKT, superoxide dismutase 1 (SOD1), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47-phox) were quantified. Changes in mitochondrial ultrastructure were examined, and mitochondrial DNA, cell viability, ROS release, oxygen consumption rate (OCR) were determined. RESULTS: Apelin-13 reduced bupivacaine-induced mitochondrial DNA lesions in SD rats (P < .001), while increasing the expression of AMPKα (P = .007) and PI3K (P = .002). Furthermore, apelin-13 blocked bupivacaine-induced depolarization of the mitochondrial membrane potential (P = .019) and the bupivacaine-induced increases in ROS (P = .001). Also, the AMPK pathway was activated by bupivacaine as well as apelin-13 (P = .002) in H9c2 cardiomyocytes. Additionally, the reduction in the PI3K expression by bupivacaine was mitigated by apelin-13 in H9c2 cardiomyocytes (P = .001). While the aforementioned changes induced by bupivacaine were not abated by apelin-13 after pretreatment with AMPK inhibitor compound C; the bupivacaine-induced changes were still mitigated by apelin-13, even when pretreated with PI3K inhibitor-LY294002. CONCLUSIONS: Apelin-13 treatment reduced bupivacaine-induced oxidative stress, attenuated mitochondrial morphological changes and mitochondrial DNA damage, enhanced mitochondrial energy metabolism, and ultimately reversed bupivacaine-induced cardiotoxicity. Our results suggest a role for the AMPK in apelin-13 reversal of bupivacaine-induced cardiotoxicity.

Transmuscular quadratus lumborum block versus oblique subcostal transversus abdominis plane block for analgesia in laparoscopic hysterectomy: a randomised single-blind trial.

OBJECTIVE: The transmuscular quadratus lumborum (TQL) block and the oblique subcostal transversus abdominis plane (OSTAP) block both contribute to multimodal analgesia after laparoscopic surgery. The objective of this study was to compare the analgesic effects of the TQL block versus OSTAP block after laparoscopic hysterectomy. DESIGN: Prospective single-centre randomised single-blind trial. SETTING: University-affiliated hospital. PARTICIPANTS: Patients aged between 18 and 65 years scheduled for laparoscopic hysterectomy. INTERVENTIONS: Patients were randomised into two groups (1:1 ratio) and received bilateral TQL block or bilateral OSTAP block with 0.375% ropivacaine 20 mL on each side before surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the cumulative morphine dose in the first 24 hours. The secondary outcome measures were the morphine consumption at each time interval after surgery, the time from the end of surgery to the first need for morphine, the Numerical Rating Scale (NRS) scores for visceral and incisional pain intensity, and the incidence of adverse events. RESULTS: The cumulative morphine dose was significantly lower in the TQL group than in the OSTAP group (17.2 (12.5) vs 26.1 (13.3) mg, p=0.010). Compared with the OSTAP group, the morphine doses from 6 to 12, 12 to 18, and 18 to 24 hours were significantly lower, the time of first need for morphine was significantly longer and the NRS scores for visceral pain intensity were significantly lower in the TQL group. CONCLUSION: Compared with the OSTAP block, the TQL block reduced morphine consumption and provided better visceral pain relief with a longer duration of effect after laparoscopic hysterectomy. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1800017995); pre-results.

Comparison of the effect of different volumes ropivacaine on deep serratus anterior plane block in patients undergoing breast surgery: a prospective randomized double-blinded trial.

BACKGROUND: A larger volume of local anesthetic provides a wider range of blocked sensory but carries a greater risk. The purpose of this trial was to compare the effect of different volumes of ropivacaine injected to deep serratus anterior plane in patients undergoing breast surgery. METHODS: In this randomized double-blind trial, 60 patients undergoing breast surgery were randomly allocated to R10, R20 and R30 groups (n=20), and received deep serratus anterior plane block with 10, 20 and 30 mL of 0.5% ropivacaine respectively. 30 minutes after block, the cutaneous sensory was tested by cold stimulus in the craniocaudal direction along the midaxillary line. We recorded the numerical rating scale pain scores over 24 h after surgery and estimated the area under curve by numerical rating scale pain scores. The cases of rescue analgesia and the prevalence of adverse events were also recorded. RESULTS: The blocked dermatomes were 3 [3, 4], 6 [5, 7] and 7 [6, 8] in the R10, R20 and R30 groups, respectively (R10 vs. R20, P<0.001; R10 vs. R30, P<0.001; R20 vs. R30, P=0.005). The area under curve of R10 group was significantly higher compared with the R20 and R30 groups (P=0.014, P=0.003, at rest; P<0.001, P<0.001, on movement). CONCLUSIONS: The blocked dermatomes increased with increasing volume when 10, 20 and 30 mL ropivacaine was used for deep serratus anterior plane block. The analgesic effects of 20 and 30 mL were similar to each other and better than 10 mL. Therefore, in breast surgery, volume of 20 mL ropivacaine is considered to be appropriate for deep serratus anterior plane block.

[Advances in Hyperprogressive Disease in Patients 
with Advanced Non-small Cell Lung Cancer Treated with Immunotherapy].

Hyperprogressive disease (HPD) is a novel pattern of progression caused by immune checkpoint inhibitors (ICIs). It is characterized by a dramatic tumor surge and is associated with poor clinical outcomes. Up to now, the definition of HPD is still controversial across various studies. Although it has been indicated that HPD has related to multiple clinicopathological features and genetic alterations, it is lack of biomarker to predict its occurrence, and the potential mechanism remains unknown. This review is to summarize current data on HPD specialized in the field of non-small cell lung cancer. And we expect to provide helpful clinical strategies for oncologists using ICIs.
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