Rejected

Chronic pain is one of the most prevalent health problems. The establishment of chronic pain is complex. Current medication for chronic pain mainly dependent on anticonvulsants, tricyclic antidepressants and opioidergic drugs. However, they have limited therapeutic efficacy, and some even with severe side effects. We turned our interest into alkaloids separated from traditional Chinese medicine (TCM), that usually act on multiple drug targets. In this article, we introduced the best-studied analgesic alkaloids derived from TCM, including tetrahydropalmatine, aloperine, oxysophocarpine, matrine, sinomenine, ligustrazine, evodiamine, brucine, tetrandrine, Stopholidine, and lappaconitine, focusing on their mechanisms and potential clinical applications. To better describe the mechanism of these alkaloids, we adopted the concept of drug-cloud (dCloud) theory. dCloud illustrated the full therapeutic spectrum of multitarget analgesics with two dimensions, which are "direct efficacy", including inhibition of ion channels, activating γ-Aminobutyric Acid/opioid receptors, to suppress pain signal directly; and "background efficacy", including reducing neuronal inflammation/oxidative stress, inhibition of glial cell activation, restoring the balance between excitatory and inhibitory neurotransmission, to cure the root causes of chronic pain. Empirical evidence showed drug combination is beneficial to 30-50% chronic pain patients. To promote the discovery of effective analgesic combinations, we introduced an ancient Chinese therapeutic regimen that combines herbal drugs with "Jun", "Chen", "Zuo", and "Shi" properties. In dCloud, "Jun" drug acts directly on the major symptom of the disease; "Chen" drug generates major background effects; "Zuo" drug has salutary and supportive functions; and "Shi" drug facilitates drug delivery to the targeted tissue. Subsequently, using this concept, we interpreted the therapeutic effect of established analgesic compositions containing TCM derived analgesic alkaloids, which may contribute to the establishment of an alternative drug discovery model.

Tonsillectomy is a frequently performed surgical procedure in children, requiring post-operative analgesia. This study evaluated the efficacy and safety of nalbuphine or sufentanil combined with dexmedetomidine for patient-controlled intravenous analgesia (PCIA) after pediatric tonsillectomy adenoidectomy. A total of 400 patients undergoing tonsillectomy with and without adenoidectomy were included in the study. Patients received a PCIA pump (0.5 mg/kg nalbuphine, 2 μg/kg dexmedetomidine and 0.9% sodium chloride to a total volume of 100 ml) for postoperative pain management were classified into Group ND (n = 200). Patients received a PCIA pump (2 μg/kg sufentanil, 2 μg/kg dexmedetomidine and 0.9% sodium chloride to a total volume of 100 ml) for postoperative pain management were classified into Group SD (n = 200). More stable hemodynamic changes were noted in Group ND than Group SD from 1 h to 48 h after operation. At 6, 12, 24, and 48 h after operation, the children in Group ND had higher Ramsay sedation scores than those in Group SD. The times to push the PCIA button in Group ND and Group SD were 2.44 ± 0.74 and 2.62 ± 1.00, showing significant differences ( = 0.041). The VASR scores of children in Group ND were significantly lower within 6, 12, and 24 h than those in Group SD ( < 0.05). The VASC scores of children in Group ND were significantly lower within four time points (2, 6, 12, and 24 h) than those in Group SD ( < 0.05). At 1st day after surgery, the children in Group ND had lower levels of serum ACTH, IL-6, and COR levels than those in Group SD ( < 0.001). The incidence rates of nausea and vomiting, and pruritus were significantly higher in Group SD than Group ND (5.00% vs. 11.00%, = 0.028; 1.00% vs. 4.50%, = 0.032). The total incidence rate of adverse reactions was significantly higher in Group SD than Group ND (15.00% vs. 31.00%, = 0.0001). The study demonstrated that dexmedetomidine added to nalbuphine PCIA enhanced the analgesic effects, attenuated the postoperative pain, and reduced the stress response after pediatric tonsillectomy adenoidectomy.

Few studies have described segmental thoracic spinal anesthesia (STSA) as primary anesthesiologic method in breast and axillary surgery, documenting the association of intrathecal local anesthetics and opioids. This case series reports an opioid-free scheme of STSA in four elderly patients undergoing major breast and axillary oncological surgery.

Inflammatory Myofibroblastic Tumors (IMTs) are rare fibroblastic/myofibroblastic neoplasms that affect predominately pediatric patients and young adults. Almost half of the patients with IMTs have a chromosomal abnormality in the Anaplastic Lymphoma Kinase 1 gene on chromosome 2p23. Although these tumors occur primarily in the lung, lesions have been reported in a variety of intra-abdominal organs like the liver, spleen, and mesentery. Small bowel IMTs are particularly rare. IMTs generally pursue a benign clinical course, however intra-abdominal and retroperitoneal tumors have typically shown higher local recurrence and even distant metastases. The most common presenting symptoms of an intra-abdominal IMT are abdominal pain and change in bowel habits. Laboratory results are nonspecific and can include anemia and minor elevation of inflammatory markers like C-reactive protein. We report an unusual case of IMT in the small bowel causing the obstruction.

Despite advances in the diagnosis and management, cryptococcal meningitis (CM) is still associated with high mortality due to insufficient knowledge about clinical characteristics and risk factors for poor outcomes. The aim of the present study is to provide additional evidence for regarding clinical characteristics, diagnosis, and factors associated with increased risk of mortality in CM patients.

To investigate the effects of silver foam combined with Dermlin wound healing dressing on concentrations of inflammatory factors of wound surface and quality of life of the patients with diabetic lower limb ulcers.

Some research has suggested that dental plaque and saliva could be reservoirs of () and be capable of infecting or re-infecting the gastric mucosa after eradication, with certain studies showing a significant association between PD and gastric infection by this bacterium. An electronic search was performed in PubMed, EMBASE, and Web of Science databases with the terms " AND periodontal diseases"; " AND gingivitis"; " AND chronic periodontitis"; " AND periodontitis"; " AND dental plaque", to identify articles up to September 2021. The Newcastle-Ottawa scale was used to assess study quality. A meta-analysis was performed using RevMan 2020 (Cochane Collaboration) software. A total of 1,315 studies were identified and 12 were included, analyzing 226,086 patients with mean age between 10.5 and 63.4 years. The prevalence of in the oral cavity ranged from 5.4 to 83.3%. A random-effects model was used to analyze the presence of and subgroups were made according to the method of evaluation (PCR or RUT). Statistical significance was found in the overall analysis ( = 0.01). There is no clear evidence that present in oral bacterial plaque causes gastric infection and vice versa.

Complex regional pain syndrome type-I (CRPS-I) represents a type of neurovascular condition featured by severe pain in affected extremities. Few treatments have proven effective for CRPS-I. Electroacupuncture (EA) is an effective therapy for pain relief. We explored the mechanism through which EA ameliorates pain in a rat CRPS-I model. The chronic postischemic pain (CPIP) model was established using Sprague-Dawley rats to mimic CRPS-I. We found that oxidative stress-related biological process was among the predominant biological processes in affected hindpaw of CPIP rats. Oxidative stress occurred primarily in local hindpaw but not in the spinal cord or serum of model rats. Antioxidant N-acetyl cysteine (NAC) attenuated mechanical allodynia and spinal glia overactivation in CPIP model rats, whereas locally increasing oxidative stress is sufficient to induce chronic pain and spinal glia overactivation in naive rats. EA exerted remarkable antiallodynia on CPIP rats by reducing local oxidative stress via enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Pharmacological blocking Nrf2 abolished antioxidative and antiallodynic effects of EA. EA reduced spinal glia overactivation, attenuated the upregulation of inflammatory cytokines, reduced the enhanced TRPA1 channel activity in dorsal root ganglion neurons innervating the hindpaws, and improved blood flow dysfunction in hindpaws of CPIP rats, all of which were mimicked by NAC treatment. Thus, we identified local oxidative injury as an important contributor to pathogenesis of animal CRPS-I model. EA targets local oxidative injury by enhancing endogenous Nrf2-mediated antioxidative mechanism to relieve pain and inflammation. Our study indicates EA can be an alternative option for CRPS-I management.

Coronavirus disease (COVID-19) is an infectious disease that can lead to pneumonia, pulmonary oedema, acute respiratory distress syndrome, multiple organ and system dysfunction, and death. This study aimed to verify the efficacy of chest computed tomography (CT) for the initial diagnosis of COVID-19. This observational, retrospective, cross-sectional study included 259 individuals who underwent clinical evaluation, blood collection, chest CT, and a reverse transcription polymerase chain reaction (RT-PCR) diagnostic test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during their course of treatment at a reference hospital in Belém, Pará, Brazil between April and June 2020. Inclusion criteria were flu-like symptoms in adults of both sexes. Individuals with an inconclusive COVID-19 molecular test or who had artifacts in the chest CT images were excluded. Parametric data were analyzed using Student–test and non-parametric data were analyzed using average test and Fisher exact test. Participants were divided into two groups: Group 1 (COVID-19 positive), = 211 (124 males, 87 females), 51.8 ± 17.9 years old and Group 2 (COVID-19 negative), = 48 (22 males, 26 females), 47.6 ± 18.6 years old. Most frequent symptoms were cough [Group 1 = 199 (94%)/Group 2 = 46 (95%)], fever [Group 1 = 154 (72%)/Group 2 = 28 (58%)], myalgia [Group 1 = 172 (81%)/Group 2 = 38 (79%)], dyspnoea [Group 1 = 169 (80%) / Group 2 = 37 (77%)], headache [Group 1 = 163 (77%)/Group 2 = 32 (66%)], and anosmia [Group 1 = 154 (73%)/Group 2 = 29 (60%)]. Group 1 had a higher proportion of ground-glass opacity [Group 1 = 175 (83%)/Group 2 = 24 (50%), 0.00], vascular enhancement sign [Group 1 = 128 (60%)/Group 2 = 15 (31%), 0.00], septal thickening [Group 1 = 99 (47%)/Group 2 = 13 (27%), 0.01], crazy-paving pattern [Group 1 = 98 (46%) / Group 2 = 13 (27%), 0.01], consolidations [Group 1 = 92 (43%)/Group 2 = 8 (16%), 0.00], and CO-RADS 4 and 5 [Group 1 = 163 (77.25%)/Group 2 = 24 (50%), 0.00] categories in chest CT. Chest CT, when available, was found to be an efficient method for the initial diagnosis and better management of individuals with COVID-19.