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CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs.

To study the effects of Lu-tong Granules (LTG) in ICH etermine the underlying mechanism of molecular network.

The psychological flexibility model can be seen as a basis for an integrated and progressive psychological approach to chronic pain management. Some researchers suggest that psychological flexibility and inflexibility represent distinct processes and constructs. This meta-analysis is the first to provide a summary estimate of the overall effect size for the relationship between psychological (in)flexibility and common outcomes among chronic pain patients. The research protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, https://www.crd.york.ac.uk/PROSPERO/), registration number CRD42021285705. Four databases were searched (PsycINFO; PubMed; Web of Science, CINAHL) along with reference lists. Thirty-six cross-sectional studies were included (7,779 participants). Meta-analyses (random effects model) indicated a significant medium negative association between psychological flexibility and pain intensity or functional impairment. The present study also indicated a significant small to medium association between psychological inflexibility and pain intensity, a nearly large association between psychological inflexibility and functional impairment as well as the quality of life, and a large association between psychological inflexibility and anxiety/depression. Due to the limited number of included studies, the relationship between risk behavior and psychological inflexibility may not be significant. Types of countries and instruments measuring psychological inflexibility may explain part of the heterogeneity. These findings may carry significant implications for chronic pain patients regarding the potential relationship between psychological inflexibility or flexibility and these outcomes. It may consequently form the basis for more robust testing of causal and manipulable relationships.

Gynecologic emergencies may result from congenital uterine anomalies (CUAs) with outflow tract obstruction. Not limited to the "classic" presentation of an adolescent amenorrheic pain patient, such anomalies should be part of the differential diagnosis for adult female patients presenting with severe pelvic pain. Obstructed rudimentary noncommunicating cavitary horns may result in severe chronic or acute pain and necessitate urgent surgical management. While two-dimensional (2D) ultrasound is often the initial diagnostic tool, three-dimensional (3D) ultrasound and MRI can accurately delineate CUAs for definitive diagnosis. When excision of a rudimentary horn is required, a laparoscopic approach is preferable. This case series focuses on two adult patients with severe pelvic pain due to unicornuate uteruses with obstructed noncommunicating cavitated rudimentary horns. Both cases involve a delayed diagnosis, the inability to make the diagnosis at standard surgical observation, and the resultant need for urgent surgical management.

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively normal volunteers (n = 25), patients with mild AD dementia (n = 16), and patients with epilepsy who underwent intracranial electrode monitoring (n = 2) to assess safety and feasibility of a single brief GENUS session to induce entrainment and (2) a single-blinded, randomized, placebo-controlled Phase 2A pilot study (NCT04055376) in patients with mild probable AD dementia (n = 15) to assess safety, compliance, entrainment, and exploratory clinical outcomes after chronic daily 40Hz sensory stimulation for 3 months. Our Phase 1 study showed that 40Hz GENUS was safe and effectively induced entrainment in both cortical regions and other cortical and subcortical structures such as the hippocampus, amygdala, insula, and gyrus rectus. Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both the control and active groups, with participants equally inaccurate in guessing their group assignments prior to unblinding. Electroencephalography recordings show that our 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD dementia. After 3 months of daily stimulation, the group receiving 40Hz stimulation showed (i) lesser ventricular dilation and hippocampal atrophy, (ii) increased functional connectivity in the default mode network as well as with the medial visual network, (iii) better performance on the face-name association delayed recall test, and (iv) improved measures of daily activity rhythmicity compared to the control group. These results support further evaluation of GENUS in a pivotal clinical trial to evaluate its potential as a novel disease-modifying therapeutic for patients with AD.

Gut microbiota alterations are strongly associated with prescription opioid use (POU) and multisite chronic pain (MCP). However, whether or not these associations are causal remains unknown. Therefore, we aim to explore the causal relationships between them comprehensively.

Agenesis of the internal carotid artery (ICA) is a rare vascular condition that is complicated by intracranial aneurysms and rete mirabile. The altered hemodynamics caused by this distinctive cerebrovascular angioarchitecture can cause ischemic or hemorrhagic accidents. Data on clinical and radiographic features have been limited to describing this vascular pattern. We present five cases of agenesis of the internal carotid artery confirmed by digital subtraction angiography (DSA) and further investigate the influence of altered angioarchitecture on the integrity of intracranial morphology.

Pain in its various forms is undoubtedly the most common ailment known to human beings. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are widely used to treat pain. However, long-term use of NSAIDs and opioids causes serious adverse effects on various organs. As a result, looking for drugs with better efficacy and lesser adverse effects appears crucial. For this purpose the obvious search begins from traditional medicines, particularly herbs. Therefore, this study investigated analgesic and anti- inflammatory activity of 80% methanol root extract of Benth (VS) in vivo.

Tumor growth or bone metastases in cancer patients all can induce bone cancer pain. It is frequently occurred in patients with breast, prostate, and lung cancer. Because of the lack of effective treatment, bone cancer pain causes depression, anxiety, fatigue, and sleep disturbances in cancer patients, disrupts the daily quality of life, and results in huge economic and psychological burden. Over the past years, transient receptor potential channels (TRPs), especially TRP vanilloid 1 (TRPV1) in dorsal root ganglion (DRG), have been considered to be involved in bone cancer pain. The characteristic of TRPV1 had been well studied. The mechanisms under TRPV1 regulation in DRG with bone cancer pain are complex, including inflammatory mediators, endogenous formaldehyde, and other mechanisms. In the present review, we summarize the role and potential mechanism of TRPV1 in DRG in bone cancer pain. As the primary sensory neurons, targeting the TRPV1 channel in DRG, might have fewer side effects than in central. We hope systematically understand of TRPV1 modulation in DRG will bring more effective strategy.

It is known that exercise can be one of the causes of muscular damage. In recent times, physiotherapists and medical professionals have been employing USGET techniques to stimulate muscle recovery to improve its performance after the injury. We pretend to analyse if the Ultrasound-guided electrolysis (USGET) technique could reduce muscle damage, inflammation, and pain in the present study. Female Wistar rats were assigned to one of three different groups: control (C), notexin (NOT) and notexin with USGET (electrolysis at 6mA) (NOT+USGET). We used the USGT technique, based on electrical stimulation with a continuous current of 4 pulses at an intensity of 6 mA for 5 seconds, conveyed to the muscle. The response was tested with motor function tests. In these tests, we could observe an increase in time and foot faults when crossing a beam in the NOT group compared to C group rats. On the other hand, a significant decrease in both variables was detected in the NOT+USGET compared to the NOT group. Muscle power was measured with a grip strength test, obtaining far better performances in NOT+USGET rats when compared to NOT rats. Moreover, the USGET technique prevented the increase of pro-inflammatory proteins IL-6 and chemokines CCL3 (Chemokine (C-C motif) ligand 3), CCL4 (Chemokine (C-C motif) ligand 4), and CCL5 (Chemokine (C-C motif) ligand 5) with their receptor CCR5 (C-C chemokine receptor type 5), induced by notexin in the quadriceps. At the same time, the study evidenced a decrease in both CCR8 (C-C chemokine receptor type 5,) and NF-ᴋB (nuclear factor- ᴋB) expressions after USGET treatment. On the other hand, we obtained evidence that demonstrated anti-inflammatory properties of the USGET technique, thus being the increase in IL-10 (Interleukin 10) and IL-13 (Interleukin 13) in the NOT+USGET group compared to the NOT group. Furthermore, when applying NSGET after damage, an increase in anti-inflammatory mediators and reduction of pro-inflammatory mediators, which, overall, promoted muscle regeneration, was observed. These results support the idea that the NSGET technique improves muscle recovery after toxic damages, which would justify its employment.