Traditional Chinese Medicine Regulates Autophagy to Prevent and Treat Osteoarthritis： A Review / 中国实验方剂学杂志

Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.

A case of Aspergillus salwaensis-induced spinal infection / 中国热带医学

@#Abstract: To report a case of Aspergillus salwaensis-induced spinal infection and its laboratory detection. The inflammatory granulation and necrotic tissue samples of a patient with spinal infection were collected from, the Affiliated Hospital of Chengde Medical College on June 17, 2020 for direct smear microscopy and culture, and the isolated strain was identified by microscopy by smear staining, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF-MS), molecular identification and in vitro antifungal susceptibility test. The patient was 62 years old female and presented with recurrent chest and back pain with no obvious cause. The initial diagnosis was spinal infection, after 7 days of treatment with levofloxacin, the effect was not good. Surgery was then performed remove the lesion via posterior thoracic debridement, and fungal hypha was observed under microscope in tissue specimens. The isolated strains had no typical structure, MALDI-TOF-MS was used for identification for many times, but there was no identification result. After 7 days of fluconazole treatment, the patient's condition improved, and her chest and back pain were alleviated compared to before surgery. The patient was discharged and followed up in the outpatient department, the fungus was later identified as Aspergillus salwaensis by sequence analysis of the internal transcribed spacer (ITS) gene sequencing, and the patient's antifungal medication was changed to voriconazole after with the attending physician. The patient consciously recovered well with no pain in the operative area and normal spinal activity at 1 year follow-up. The possibility of spinal fungal infection should be considered in patients with back pain without a clear cause and poor response to routine antibiotic treatment. Direct smear report of microscopic results are very important for guiding clinical antibiotic selection for rare filament fungi with atypical colony and microscopic morphology and unsuccessful MALDI-TOF-MS identification, molecular biological methods such as ITS sequence analysis can be helpful for early identification of the fungal species, improving identification speed.

Supramalleolar Osteotomy Combined with Redo Arthroscopy for a Patient with Persistent Pain after Primary Arthroscopic Microfracture for Medial Osteochondral Lesion of the Talus: A Case Report / 대한족부족관절학회지

A medial opening wedge supramalleolar osteotomy (SMO) introduced by Takakura et al. is a useful realignment procedure for patients with ankle joint arthritis and varus malalignment by shifting the weight-bearing axis laterally and redistributing the loads on the ankle joint. When pain persists after arthroscopic microfracture in patients with medial osteochondral lesion of the talus (OLT), redo arthroscopy, osteochondral autograft transplantation, autologous chondrocyte implantation, or matrix-induced chondrogenesis might be indicated. On the other hand, there is insufficient scientific evidence for realignment surgery through SMO, while the effect of realignment surgery has been studied consecutively for osteochondral lesions of the knee. Therefore, this paper reports a patient with medial OLT who underwent redo arthroscopy combined with SMO for persistent pain after primary arthroscopic microfracture.

Clinical observation of Ruyi jinhuang powder combined with ICIs in the treatment of advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder / 中国药房

OBJECTIVE To explore the clinical efficacy and safety of Ruyi jinhuang powder for external application combined with immune checkpoint inhibitors （ICIs） in the treatment of patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder. METHODS All patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder were admitted to our hospital from January 2018 to June 2022 and assigned into observation group and control group according to random number table method. Patients in the control group （n＝56） were treated with ICIs （Navulizumab injection/Sintilimab injection/Camrelizumab for injection） 200 mg， ivgtt， 21 days as a treatment cycle. Patients in the observation group （n＝56） were additionally treated with Ruyi jinhuang powder for external application， once a day， on the basis of control group. The therapeutic effects of 2 groups were compared after a treatment cycle. The levels of interleukin-6 （IL- 6）， matrix metalloproteinase-9 （MMP-9）， cyclooxygenase-2 （COX-2）， prostaglandin E2 （PGE2）， carbohydrate antigen 199 （CA199）， alpha-fetoprotein （AFP） and vascular endothelial growth factor （VEGF） in serum were compared between 2 groups before and after treatment. Karnofsky functional status （KPS） score， digital rating scale （NRS） score， total symptom score of traditional Chinese medicine， and the occurrence of adverse reactions were recorded for both groups of patients. RESULTS After treatment， the levels of IL-6， MMP-9， COX-2， PGE2， CA199， AFP， VEGF， NRS score and total symptom score of traditional Chinese medicine in observation group were significantly lower than control group （P＜0.05）， KPS score was significantly higher than the control group （P＜0.05）. The zypp-04） total effective rate and remission rate of the observation group were 64.29% and 80.36%， those of control group were 60.71% and 73.21%. There was no statistical significance between two groups （P＞0.05）. The adverse drug reactions of both groups were mainly nausea and vomiting， liver function injury， fever hlshli@yeah.net and so on； the incidence of adverse reaction in observation group was significantly lower than that of control group （P＜0.05）. CONCLUSIONS In patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder， the combination of Ruyi jinhuang powder for external application and ICIs can help inhibit the secretion of pain mediators， regulate vascular endothelial function， reduce the inflammatory response， promote the recovery of cardiopulmonary function， improve clinical efficacy and has good safety.

Clinical observation of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis in the early and mid-term stage / 中国药房

OBJECTIVE To investigate clinical efficacy and safety of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis （KOA） in the early and mid-term stage. METHODS Totally 100 KOA patients were randomly divided into control group and trial group， with 50 cases in each group. Control group received Diacerein capsules orally， 50 mg every time， bid. Trial group additionally received Jipei dilong ointment， once a day， on the basis of control group. Both groups had a treatment course of 4 weeks， and were followed up for 3 months after treatment. The clinical efficacy of 2 groups， visual analogue scale （VAS）， Western Ontario and McMaster University osteoarthritis index （WOMAC） score， Lysholm scores before and after treatment， at 3-month follow-up after treatment were all observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin 1β （IL-1β）， IL-6， superoxide dismutase （SOD）， malondialdehyde （MDA）， nitric oxide （NO）， cartilage oligomeric matrix protein （COMP）， matrix metalloproteinase-13 （MMP-13） and C-telopeptide of type Ⅱ collagen （CTX-Ⅱ） were detected in knee joint fluid. The incidence of adverse drug reactions was recorded. RESULTS After 4 weeks of treatment， total effective rate was 96.0% in trial group and 90.0% in control group， without statistical significance between 2 groups （P＞0.05）. At 3- 2019YFC1712500） month follow-up after treatment， total effective rate of trial group was 94.0%， and was higher than 62.0% of control group（P＜0.05）. After 4 weeks of treatment and at 3-month follow-up after treatment， VAS score， WOMAC score，the contents ofTNF-α， IL-1β， IL-6， MDA， NO， COMP， MMP-13 and CTX-Ⅱ in knee joint fluid of two groups were significantly lower than before； Lysholm score and SOD activity of knee joint fluid were significantly higher than before， and the trial group was significantly better than the control group during the same period （P＜0.05）. And there was no statistical significance in the incidence of adverse drug reactions between two groups（P＞0.05）. CONCLUSION For the treatment of KOA in early and mid- term stage， Jipei dilong ointment combined with diacerein relieve pain， improve knee function by inhibiting inflammatory reaction， reducing oxidative stress and inhibiting chondrocyte and matrix degradation， and have low incidence of adverse drug reactions.

Roles of focal adhesion proteins in skeleton and diseases

The skeletal system, which contains bones, joints, tendons, ligaments and other elements, plays a wide variety of roles in body shaping, support and movement, protection of internal organs, production of blood cells and regulation of calcium and phosphate metabolism. The prevalence of skeletal diseases and disorders, such as osteoporosis and bone fracture, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, increases with age, causing pain and loss of mobility and creating a huge social and economic burden globally. Focal adhesions (FAs) are macromolecular assemblies that are composed of the extracellular matrix (ECM), integrins, intracellular cytoskeleton and other proteins, including kindlin, talin, vinculin, paxillin, pinch, Src, focal adhesion kinase (FAK) and integrin-linked protein kinase (ILK) and other proteins. FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell-environment communications and modulates important processes, such as cell attachment, spreading, migration, differentiation and mechanotransduction, in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways. This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.

Mechanism of Honghua Oral Liquid in Alleviating Neuropathic Pain / 中国实验方剂学杂志

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Traditinal Chinese Medicine Intervention in Intervertebral Disc Degeneration by Regulating Matrix Metalloproteinase Expression： A Review / 中国实验方剂学杂志

Intervertebral disc degeneration is one of the common causes of chronic low back pain. As a common spinal disease， its clinical symptoms are mainly low back pain and limited function， which seriously affects physical and psychological health. Because of its complex and unclear pathogenesis， the treatment of intervertebral disc degeneration has been the focus of scientific researchers and clinical workers. At present， the treatment of intervertebral disc degeneration mainly includes non-surgical therapy and surgical therapy， which can alleviate the clinical symptoms of patients to a certain extent， but easily induce new complications， and it is difficult to restore the normal physiological function of the intervertebral disc. In recent years， along with the advanced research on matrix metalloproteinases （MMPs） in the tissues of intervertebral disc degeneration， it has been found that MMPs can be used as molecular therapeutic targets. The expression of MMPs in the intervertebral disc tissues can be regulated by reducing the content and composition of the extracellular matrix of the intervertebral disc， so as to slow down intervertebral disc degeneration and even reverse the occurrence of intervertebral disc degeneration. This treatment is expected to delay intervertebral disc degeneration caused by changes in extracellular matrix composition or content. In recent years， with the continuous development of network pharmacology and bioinformatics research， a large number of researchers have explored the treatment of intervertebral disc degeneration by traditional Chinese medicine （TCM） and found that TCM can reduce the degradation of extracellular matrix by inhibiting the expression of MMPs， thus alleviating the symptoms of intervertebral disc degeneration and slowing down the progression of intervertebral disc degeneration. This paper reviewed the research progress of TCM intervention in MMP expression in the treatment of intervertebral disc degeneration， aiming at providing references for the application of TCM in the prevention and treatment of intervertebral disc degeneration.

Effects of etoricoxib and sodium hyaluronate on pain and inflammatory factors in patients with knee osteoarthritis / 中国医师进修杂志

Objective:To explore the effects of etoricoxib combined with sodium hyaluronate on pain and inflammatory factors in patients with knee osteoarthritis (KOA).Methods:A total of 106 KOA patients admitted to Zhujiang Hospital of Southern Medical University were selected as the research objects from March 2018 to October 2020, and they were divided into a control group and a study group using a random number table method, with 53 cases in each group. The control group was treated with sodium hyaluronate, and the study group was treated with etoricoxib on the basis of the control group. The effects of both groups were observed after continuous treatment for 4 weeks. The clinical efficacy and changes of knee joint function, pain and inflammatory factors before and after treatment were compared between the two groups, and the occurrence of adverse reactions during the treatment period was recorded.Results:The total effective rate of the study group was higher than that of the control group: 92.45%(49/53) vs. 77.36%(41/53), the difference was statistically significant ( P<0.05). The American Knee Association score (AKS) and Lysholm score after treatment in the two groups were higher than before treatment ( P<0.05), and the AKS score and Lysholm score in the study group after treatment were higher than control group: (171.84 ± 24.16) scores vs. (159.09 ± 22.21) scores, (81.62 ± 14.76) scores vs. (75.41 ± 13.58) scores, the difference was statistically significant ( P<0.05). The visual analogue score (VAS) of pain after treatment in the two groups was lower than before treatment, and the VAS score of the study group after treatment was lower than the control group: (3.01 ± 0.54) scores vs. (3.45 ± 0.64) scores. the difference was statistically significant ( P<0.05). The levels of interleukin-1β (IL-1β), matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) after treatment in the two groups were lower than before treatment, TIL-1β, MMP-3, and MMP-9 of the study group after treatment were lower than the control group: (56.38 ± 9.67) μg/L vs. (62.19 ± 10.73) μg/L, (91.56 ± 15.18) μg/L vs. (98.09 ± 16.74) μg/L, (30.46 ± 5.59) μg/L vs. (35.03 ± 6.27) μg/L, the difference was statistically significant ( P<0.05). There was no statistically significant difference in the incidence of total adverse reactions between the two groups ( P>0.05). Conclusions:Tocoxib combined with sodium hyaluronate in the treatment of KOA can improve the clinical efficacy, improve knee joint function, relieve pain, reduce the level of inflammatory factors, and have good safety.

Electroacupuncture improves motor function of rats with osteoarthritis by alleviating joint inflammation through the Wnt-7B/β-catenin signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of electroacupuncture on osteoarthritis in rats and explore the possible mechanism.@*METHODS@#Thirty SD rats were randomly divided into osteoarthritis model group, electro-acupuncture group and control group (n=10), and in the former two groups, early osteoarthritis was induced using a modified DMM surgical modeling method. After successful modeling, the rats in the electro-acupuncture group were treated with electro-acupuncture at bilateral "Housanli" and "Anterior knee point". Behavioral tests of the rats were performed and scored using the LequesneMG scale. Subchondral bone degeneration was observed in each group, and serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP were measured using ELISA. The mRNA and protein expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7, and MMP-3 in the cartilage tissue of the knee joints were detected using RT-PCR and Western blotting.@*RESULTS@#In behavioral tests, the rats in the model and electroacupuncture groups had significantly higher LequesneMG scores after modeling than those in the control group (P < 0.05). After 20 days of treatment, LequesneMG scores were significantly lowered in rats in the electroacupuncture as compared with the model rats (P < 0.05). Imaging examination revealed obvious subchondral bone damage in both the electroacupuncture group and the model group, but the damages were significantly milder with former group. Compared with the model rats, the rats receiving electroacupuncture had significantly lower serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP (P < 0.05) with also lower expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7 and MMP-3 in the cartilage tissues at both the mRNA and protein levels (P < 0.05).@*CONCLUSION@#Electroacupuncture can alleviate joint pain and improve subchondral bone damage in rats with osteoarthritis by reducing IL-1β levels in the joint cartilage tissue and serum to alleviate joint inflammation and by reducing such cytokines as ADAMTS-7 and MMP-3 via regulating the Wnt-7B/β-catenin signaling pathway.

Analysis of the effect of midazolam on pain in a rat model of lumbar disc herniation based on the p38 MAPK signaling pathway / 中国骨伤

OBJECTIVE@#To investigate the effect of midazolam on pain in lumbar disc herniation model rats based on p38 MAPK signaling pathway.@*METHODS@#Fifty SPF-grade Sprague-Dawley healthy rats, half male and half female, were selected and randomly divided into normal group, model group, and low-dose, medium-dose, high-dose groups. Model group and low-dose, medium-dose, high-dose groups were initially modeled for lumbar disc herniation. Intraperitoneal injection of saline was performed in rats of normal and model groups; and in the low-dose, medium-dose, and high-dose groups, intraperitoneal injection of midazolam was performed with doses of 30, 60, and 90 mg/kg, respectively. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), substance P (SP), neuropeptide Y (NPY) were detected in the serum of rats by enzyme-linked immunoassay. The expression of p38 MAPK and matrix metalloproteinase-3(MMP-3) protein were detected by Western blot in the tissues of rats of each group.@*RESULTS@#The levels of TNF-α, IL-1β and β-EP were higher and the level of 5-HT was lower in the model group than in the normal group(P<0.05);the levels of TNF-α, IL-1β and β-EP were lower and the level of 5-HT was higher in the low-dose, medium-dose and high-dose groups than in the model group(P<0.05). The levels of SP and NPY increased in the model group compared with the normal group (P<0.05) and the levels of SP and NPY decreased in the low-dose, medium-dose and high-dose groups compared with the model group (P<0.05). The expression of p38 MAPK and MMP-3 increased in the model group compared with the normal group (P<0.05); the expression of p38 MAPK and MMP-3 decreased in the low-dose, medium-dose and high-dose compared with the model group(P<0.05).@*CONCLUSION@#Midazolam may ameliorate the immune inflammatory response in rats with a model of lumbar disc herniation, possibly regulated through the p38MAPK signaling pathway.

Application of acellular dermal matrix in periodontal soft tissue augmentation surgery / 中华口腔医学杂志

The substitute materials of autologous tissue graft for periodontal soft tissue augmentation surgery develop rapidly. The use of substitute material can avoid the second operation area, shorten the operation time, reduce the postoperative reaction and pain, and is not limited by the quantity, suitable for a wide range of cases. In this paper, the characteristics, histological study, clinical application and therapeutic effect of acellular dermal matrix as a substitute material for autologous tissue transplantation were introduced to provide reference for clinical work.

Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro / 中国中药杂志

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities

Background@#Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%–69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. @*Methods@#A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twentyeight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. @*Results@#The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. @*Conclusions@#The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Intervention Effect of Qufeng Gutong Babu Ointment on Rat Model of Osteoarthritis with Cold-dampness Obstruction Based on PI3K/Akt Signal Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Qufeng Gutong Babu ointment （QFGT） on rats with osteoarthritis （OA） with cold-dampness obstruction， and preliminarily clarify its mechanism. MethodSD male rats were divided into 6 groups， namely， the blank group， model group， positive control drug Huoxue Zhitong ointment （HXZTG） group （1.26 cm2·d-1）， and low， medium， and high-dose QFGT group （75， 150， 300 mg·d-1）. OA model was prepared by joint cavity injection of papain and L-cysteine. On the second day of modeling， climate factors were applied to establish an animal model of combination of disease and syndrome of OA rats with cold-dampness obstruction. Standard VonFrey fiber was used to evaluate the threshold of mechanical pain. Weight bearing difference score and joint function score of both hind limbs were recorded. Hematoxylin-eosin （HE） staining and safranine fixation green staining were used to observe the pathological changes and cartilage degeneration of rat knee joint. Immunohistochemistry （IHC） was used to detect the expression of interleukin-1β （IL-1β）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， matrix metalloproteinase-9 （MMP-9）， and cathepsin K （CTSK）. Western blot was used to detect the protein expression of kinase B （Akt）， phosphorylated protein kinase B （p-Akt）， phosphatidylinositol 3-kinase （PI3K）， nuclear factor 1 （NFATc1）， MMP-9， and CTSK in T cells. ResultCompared with the normal group， the model group showed significant mechanical pain sensitivity reaction after modeling （P<0.01）， and the weight bearing difference of both hind limbs and joint function score were significantly increased （P<0.05， P<0.01）. Compared with the model group， both the high-dose QFGT group and the HXZTG group significantly reduced the mechanical pain sensitivity， weight difference， and joint function score of rats （P<0.05， P<0.01）， and the medium-dose QFGT group also improved the joint function to a certain extent， and the degeneration of the knee joint cartilage of rats was significantly reduced （P<0.05， P<0.01）. QFGT and HXZTG both inhibited the protein expression of IL-1β， IL-8， TNF-α， MMP-9， CTAK， PI3K， p-Akt， Akt， and other related proteins in articular cartilage of rats with OA to a certain extent （P<0.05， P<0.01）. ConclusionQFGT can inhibit the release of inflammatory factors and matrix metalloproteinases by inhibiting the PI3K/Akt signal pathway in articular articular cartilage of rats with OA with cold-dampness obstruction， thus ultimately weakening local cartilage degeneration and improving joint function.

O ensino de cuidados paliativos na graduação do curso de medicina: um olhar multicêntrico / The teaching of palliative care in undergraduate medicine courses: a multicentric view / La enseñanza de cuidados paliativos en cursos de pregrado en medicina: una visión multicéntrica

Cuidados Paliativos (CP) consiste em uma modalidade multiprofissional onde pacientes fora de possibilidade de cura e sua família, recebem cuidados totais, ativos e integrais amparados pelo direito do paciente de morrer com dignidade. Apesar de ser uma modalidade assistencial crescente no mundo, ainda é pouco abordada na formação médica brasileira. Os objetivos do presente trabalho são discutir a importância da incorporação do tema na formação médica sob a luz da legislação vigente, a visão e o cuidado ofertado pelos CP e apresentar como sugestão uma disciplina sobre cuidados paliativos para a matriz curricular do curso de medicina. O avanço das tecnologias médicas tem prolongado e, possibilitado melhorias para a qualidade de vida da população, mesmo diante de casos de doenças graves, sem possibilidade terapêutica, incapacitantes e progressivas. A formação adequada de profissionais médicos com os recursos da paliação tem exigido que escolas médicas atendam às necessidades de saúde dos pacientes e de seus familiares. Estudantes de medicina devem ter acesso à comunicação compassiva e efetiva com pacientes, gerenciamento de dor e outros sintomas, princípios e boas práticas de cuidados paliativos. O conhecimento dos critérios para indicação de cuidados paliativos precoces e o manejo dos cuidados de fim de vida incluindo, além do controle de sintomas de sofrimento físico, a abordagem de aspectos psicossociais, espirituais e culturais dos pacientes e a identificação de riscos potenciais de luto são primordiais para a prática. Diante disso, a necessidade da inserção do ensino em CP na graduação tornou- se evidente, culminando nas publicações de Resoluções para abranger as prerrogativas previstas nas Diretrizes Curriculares Nacionais (DCNs) para o Curso de medicina. Essa discussão torna-se fundamental diante do cenário que atravessamos com a expansão de escolas médicas no país. Discute-se que uma proposta multicêntrica de disciplina transversal sobre cuidados paliativos inserida na matriz curricular do curso de medicina como um modelo factível para a sua abordagem.

Palliative Care (PC) consists of a multidisciplinary modality where patients beyond the possibility of cure and their families receive total, active and integral care supported by the patient's right to die with dignity. Despite being a growing care modality in the world, it is still little addressed in Brazilian medical training. The objectives of this paper are to discuss the importance of incorporating the vision and care offered by the PC into medical training and to suggest a course on palliative care to be included in the curriculum of the medical course. The advancement of medical technologies has extended and improved the quality of life of the population, even in the case of serious, disabling and progressive illnesses. Adequate preparation of medical professionals with palliation resources requires medical schools to meet the health needs of patients and their families. Medical students should have access to compassionate and effective communication with patients, management of pain and other symptoms, principles and good practices of palliative care, as well as indication criteria for early palliative care and indication and management of end-of-life care including, in addition to controlling symptoms of physical suffering, addressing psychosocial, spiritual and cultural aspects of care and also identifying potential risks of grief. In view of this, the need to insert PC teaching in graduation became evident, culminating in the new National Curricular Guidelines (NCGs), and it was precisely for this reason that this article also brings, as a multicentric proposal, a discipline on palliative care to be inserted in the curricular matrices of medical courses. It can be concluded that the incorporation of PC in the curricular matrix of the medical course will allow doctors who have just left the university to offer comfort and prevention of suffering to patients who need PC, thus improving their quality of life and that of their families.

Los Cuidados Paliativos (CP) consisten en una modalidad multidisciplinar donde los pacientes sin posibilidad de curación y sus familiares reciben una atención total, activa e integral sustentada en el derecho del paciente a morir con dignidad. A pesar de ser una modalidad de atención en crecimiento en el mundo, todavía es poco abordada en la formación médica brasileña. Los objetivos del presente trabajo son discutir la importancia de incorporar la temática en la formación médica a la luz de la legislación vigente, la visión y el cuidado que ofrece la AP y sugerir una temática sobre cuidados paliativos para la matriz curricular de la carrera de medicina. El avance de las tecnologías médicas ha prolongado y permitido mejoras en la calidad de vida de la población, incluso frente a casos de enfermedades graves, no terapéuticas, incapacitantes y progresivas. La adecuada formación de los profesionales médicos con recursos paliativos ha requerido que las facultades de medicina atiendan las necesidades de salud de los pacientes y sus familias. Los estudiantes de medicina deben tener acceso a una comunicación compasiva y efectiva con los pacientes, manejo del dolor y otros síntomas, principios de cuidados paliativos y mejores prácticas. El conocimiento de los criterios para indicar los cuidados paliativos tempranos y el manejo de los cuidados al final de la vida que incluyen, además del control de los síntomas del sufrimiento físico, el abordaje de los aspectos psicosociales, espirituales y culturales de los pacientes y también la identificación de los riesgos potenciales de duelo son esenciales para la práctica. Ante ello, se hizo evidente la necesidad de insertar la enseñanza de la CP en la graduación, culminando con la publicación de Resoluciones para dar cobertura a las prerrogativas previstas en las Directrices Curriculares Nacionales (DCN) de la Carrera de Medicina. Esta discusión se torna fundamental ante el escenario que atravesamos con la expansión de las facultades de medicina en el país. Se argumenta que una propuesta multicéntrica de una disciplina transversal sobre cuidados paliativos se inserta en la matriz curricular de la carrera de medicina como modelo factible para su abordaje. Se considera que la incorporación de la CP en la matriz curricular posibilitará que los médicos egresados de las universidades ofrezcan en el currículo las bases teóricas y prácticas para subsidiar la provisión a los pacientes de la necesidad de CP, confort, prevención del sufrimiento, mejorando así su calidad de vida y la de sus familiares.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Restoration of molars affected by molar-incisor hypomineralization using the occlusal replica technique / Restauração de molares afetados pela Hipomineralização Molar-Incisivo utilizando a técnica da réplica oclusal

ABSTRACT The aim of this study was to report the clinical case of an 8-year-old male patient seen at the Pediatric Dentistry outpatient clinic at the Universidade Federal do Paraná, Brazil, diagnosed with molar-incisor hypomineralization (MIH) after presenting with pain in teeth 16, 36, and 46, which had extensive atypical cavities and opacities on the adjacent enamel. A diagnostic wax-up of affected teeth was performed for manufacture of silicone occlusal matrix. Encapsulated high-viscosity glass ionomer cement was handled and inserted into the occlusal matrix which was fitted onto the teeth by slight finger pressure. After setting time, excess of material was removed, and occlusion was checked. A flowable resin coating material was applied, and the restorations were finished. Six months later, the restorations performed for treatment of the severe MIH lesions proved to be efficient, lowering the sensitivity reported by the patient, reshaping the teeth, improving their function, and refining dental esthetics.

RESUMO O objetivo deste estudo foi relatar um caso clínico de um paciente com diagnóstico de Hipomineralização de Molares e Incisivos (HMI). Paciente do sexo masculino, de 8 anos de idade, compareceu à clínica de Odontopediatria da Universidade Federal do Paraná com queixa de dor nos dentes 16, 36 e 46 - os quais apresentavam extensas cavitações atípicas com opacidades no esmalte adjacente. O enceramento diagnóstico dos dentes afetados foi realizado para a confecção das matrizes oclusais de silicone. Cimento ionômero de vidro de alta viscosidade encapsulado foi manipulado e inserido na matriz oclusal, a qual foi encaixada sobre os dentes, exercendo-se leve pressão digital. Após a presa do material os excessos foram removidos e a oclusão foi checada. Aplicou-se uma camada de resina fluída de cobertura e as restaurações foram finalizadas. Após seis meses, as restaurações realizadas para tratar as lesões severas de HMI mostraram-se eficazes, reduzindo a sensibilidade relatada pelo paciente, além de reestabelecerem a anatomia, função e estética dentária.

Funcionalização de matriz colágena estável em volume utilizando Fibrina Rica em Plaquetas injetável (i-PRF) para o tratamento de Recessão Gengival unitária / Volume-stable collagen matrix (VCMX) biofunctionalized wit injectable platelet-rich fibrin (i-PRF) for the treatment of single gingival recession: randomized clinical trial

Substitutos de enxerto de tecido conjuntivo têm sido amplamente utilizados para superar as limitações dos enxertos autógenos no tratamento de defeitos dos tecidos moles periodontais e peri-implantares. No entanto, o desempenho clínico desses biomateriais ainda é inferior. A biofuncionalização de matrizes colágenas usando fibrina rica em plaquetas injetável (i-PRF) foi proposta como uma estratégia para aprimorar a bioatividade e, portanto, a eficácia clínica desses substitutos mucosos. Desta forma, o objetivo deste estudo foi avaliar a eficácia do uso da matriz colágena estável em volume (FG) biofuncionalizada com i-PRF no tratamento de recessões gengivais unitárias (RGs) do ponto de vista clínico, estético e de parâmetros centrados no paciente. Para tal, foram selecionados 66 pacientes portadores de RGs unitárias RT1, os quais foram alocados aleatoriamente em um dos seguintes grupos: grupo CAF (n=22), retalho posicionado coronariamente (CAF); grupo CAF+FG (n=22), CAF associado à FG; e grupo CAF+FG+i-PRF (n=22), CAF associado à FG biofuncionalizada com i-PRF. Após 6 meses, os três grupos apresentaram taxas de recobrimento radicular significativas [CAF: 69,1% (2,02 ± 1,06 mm); CAF+FG: 67,44% (1,7 ± 0,81 mm) e CAF+FG+i-PRF: 64,92% (1,64 ± 0,80 mm), sem diferença entre os grupos (p=0,33). Os grupos que receberam os biomateriais forneceram um maior ganho em espessura de tecido queratinizado (ETQ) (CAF: 0,12 ± 0,2 mm; CAF+FG: 0,43 ± 0,24 mm; CAF+FG+i-PRF: 0,48 ± 0,25 mm; p=0,000). Não foram observadas diferenças significativas em termos de altura de tecido queratinizado em nenhum dos grupos e tempos avaliados (p>0,05). Todos os grupos apresentaram redução significativa da hipersensibilidade dentinária e melhorias nas condições estéticas (p>0,05). Também não foram observadas diferenças em termos de dor e morbidade pósoperatórias (p>0,05). Dentro das limitações do presente estudo, conclui-se que as três abordagens forneceram resultados semelhantes e satisfatórios após 6 meses de acompanhamento. A adição da FG, biofuncionalizada ou não com i-PRF, proporcionou benefícios adicionais em termos de ganho de ETQ. (AU)

Soft tissue graft substitutes have been widely used to overcome the limitations of autogenous grafts in the treatment of periodontal and peri-implant soft tissue defects. However, the clinical performance of these biomaterials is still inferior. The biofunctionalization of collagen matrices using injectable platelet-rich fibrin (i-PRF) has been proposed as a strategy to enhance the bioactivity and, therefore, the clinical efficacy of these biomaterials. Thus, the aim of this study was to evaluate the effectiveness of using biofunctionalized volume-stable collagen matrix (VCMX) with i-PRF in the treatment of single gingival recessions (GRs) from clinical, esthetic, and patient-centered parameters. For this purpose, 66 patients with single RT GRs were selected and randomly allocated to one of the following groups: CAF group (n=22), coronally advanced flap (CAF); CAF+VCMX group (n=22), CAF combined with VCMX; and CAF+ VCMX +iPRF group (n=22), CAF combined with biofunctionalized VCMX with i-PRF. After 6 months, all three groups exhibited significant root coverage rates [CAF: 69.1% (2.02 ± 1.06 mm); CAF+FG: 67.44% (1.7 ± 0.81 mm); and CAF+FG+iPRF: 64.92% (1.64 ± 0.80 mm), with no difference between the groups (p=0.33). The groups that received the biomaterials showed a greater gain in keratinized tissue thickness (KTT) (CAF: 0.12 ± 0.2 mm; CAF+FG: 0.43 ± 0.24 mm; CAF+FG+i-PRF: 0.48 ± 0.25 mm; p=0.000). No significant differences were observed in terms of keratinized tissue height in any of the groups and assessed time points (p>0.05). All groups showed a significant reduction in dentin hypersensitivity and improvements in esthetic conditions (p>0.05). No differences were also observed in terms of post-operative pain and morbidity (p>0.05). Within the limitations of this study, it is concluded that all three approaches provided similar and satisfactory results after 6 months of follow-up. The addition of VCMX, whether biofunctionalized or not with i-PRF, provided additional benefits in terms of keratinized tissue thickness gain. (AU)

The Brazilian Portuguese version of the Pregnancy Mobility Index: Cross-cultural adaptation and psychometric evaluation - a validation study

ABSTRACT BACKGROUND: The Pregnancy Mobility Index (PMI) was developed to assess mobility in pregnant women in the Netherlands. At present, no similar questionnaire is available in Brazil. OBJECTIVE: The present study aimed to translate, cross-culturally adapt, and evaluate the psychometric properties of a Brazilian PMI. DESIGN AND SETTING: The present study was a validation study conducted at the Universidade Federal do Paraná and a public maternity ward in Curitiba, Brazil. METHODS: Text translation and cross-cultural adaptation followed international guidelines. Construct validity, internal consistency, and inter- and intra-rater reliability tests included 97 women. The Pelvic Girdle Questionnaire, Multidimensional Pain Evaluation Scale, Schober's test, and lumbar spine range of motion assessment were administered on the first day. Intra-rater reliability (n = 19) was measured after 15 days. Exploratory factor analysis was performed, and the correlation matrix was analyzed using Pearson's coefficient. RESULTS: Pregnant women (88%) understood the cultural adaptation process. The internal consistency was high (Cronbach's alpha > 0.90), construct validity was moderate, with significant correlation between lumbar spine range of motion (r = 0.283-0.369) and Schober's test (r = -0.314), and high correlation between the Multidimensional Pain Evaluation Scale (r = -0.650 and -0.499) and Pelvic Girdle Questionnaire (r = -0.737). Intra- and inter-rater reliabilities were excellent (intraclass correlation coefficient = 0.932 and 0.990, respectively). CONCLUSION: The Brazilian version of the PMI was successfully translated with excellent reliability and moderate-to-high construct validity. It is an important tool for assessing mobility in pregnant women. CLINICAL TRIAL: RBR-789tps (Validation study), https://ensaiosclinicos.gov.br/rg/RBR-789tps.