The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides (MOIG) on bone loss of rheumatoid arthritis (RA) rats, and the mechanism of osteoclast function and activity induced by lipopolysaccharide (LPS). RA rats were established by injecting bovin type II collagen. The Bio-ethic Committee of Zhejiang Chinese Medical University approved all experimental protocols associated with this study (IACUC-20180410-03). The collagen-induced arthritis (CIA) rats were administered drug by gavage for 8 weeks; the femoral trabecular micro-structure changes were observed in CIA rats by micro-CT; the LPS-induced osteoclasts model further observed the effect and mechanism of anti-inflammatory osteoporosis in vitro. The results indicated that MOIG could markedly increase bone mineral density (BMD) in CIA rats, improve trabecular micro-structure. In vitro studies demonstrated that MOIG could significantly inhibit osteoclastogensis and differentiation, suppress tartrate resistant acid phosphatase (TRAP) activity, F-actin ring formation, TNF receptor associated factor 6 (TRAF6) recruitment, and inhibitor of nuclear factor kappa-Bα (IκBα) degradation as well as p65 phosphorylation, thereby repressing nuclear factor kappa-B (NF-κB) signaling pathway activation. Subsequently, MOIG effectively inhibited osteoclast nuclear factor of activated T-cells c1 (NFATc1) and cellular oncogene Fos (c-Fos) expression, as well as bone resorption related protein activity including matrix metalloprotein 9 (MMP-9) and cathepsin K (CtsK). Meanwhile, MOIG also repressed the phosphorylation expression of Janus activating kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), thereby inhibiting JAK2/STAT3 signaling pathway activation. Moreover, further studies found that MOIG could suppress glycogen synthase kinase-3β (GSK-3β) activity, and GSK-3β gene silencing could markedly inhibit oetsoclast F-actin ring formation as well as the phosphorylation expression of p65 and STAT3. Of note, compared with GSK-3β gene silencing group, there was no significant difference in the group treated with both MOIG with GSK-3β gene silencing simultaneously. Thus, the results suggested that MOIG may inhibit NF-κB signaling pathway and JAK2/STAT3 signaling pathway activation via regulating GSK-3β, thereby alleviating bone destruction in RA.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective: To investigate the regulatory effect and mechanism of specific antagonist of acid-sensitive ion channel 3 (APETx2) on visceral sensitivity in mice with post-infectious irritable bowel syndrome (PI-IBS) ． Methods: The PI-IBS model was established by National Institutes of Health (NIH) mice infected with Trichinella spiralis．Gastrointestinal transport function was assessed by measuring the time to first black stool and the number of fecal pellets collected for 6 hours ; abdominal wall withdrawal reflex (AWR) was used to assess visceral sensitivity ; the expression of calcitonin gene-related peptide ( CGRP) in the colon tissue was detected by immunohistochemistry ; the expression of brain-derived neurotrophic factor (BDNF) and CGRP mRNA in the colon tissues was detected by quantitative real time polymerase chain reaction ( qRT-PCR) ． The expression levels of acid sensing ion channel 3 (ASIC3) ，CGRP，and transient receptor potential vanilloid 1 (TRPV1) protein in brain tissue were detected by Western blot analysis. Results: Compared with the control group，the PI-IBS group significantly reduced the time of first black stool，the number of fecal particles and AWR score within 6 hours significantly increased，the protein expression of CGRP in colon tissue，BDNF and CGRP mRNA significantly increased，and the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue significantly increased．Compared with the control group，the PI-IBS group significantly reduced the time to first black stool，the number of fecal particles and AWR score within 6 hours significantly increased，the expression of CGRP protein in colon tissue，the expression of BDNF and CGRP mRNA significantly increased，and the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue significantly increased ; compared with the PI-IBS group，the first time of black stool clearance in the APETx2 group was significantly prolonged，the number of fecal particles and AWR score within 6 hours were significantly reduced，the expression of CGRP protein in colon tissue，the expression of BDNF and CGRP mRNA was significantly reduced，the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue was significantly reduced，and the difference was statistically significant (P＜0. 05) ． Conclusion APETx2 can alleviate visceral sensitivity and regulate gastrointestinal motility in PI-IBS mice by downregulating the expression of BDNF，CGRP，ASIC3 and TRPV1．APETx2 may provide a new therapeutic option for the treatment of IBS.

Objective : To analyze the application value of metagenomic next-generation sequencing (mNGS) in the detection of pathogenic bacteria in pulmonary infection ，and to provide a theoretical basis for clinical diagnosis. Methods : A retrospective study was conducted on 161 patients with suspected pulmonary infection，and samples of bronchoalveolar lavage fluid ，sputum and lung tissue were collected specimens ，pleural effusion and blood were simultaneously subjected to routine culture，respiratory pathogen nucleic acid detection and pathogenic microorgan- ism mNGS detection．The sensitivity ，specificity，positive predictive value ，and negative predictive value of the three detection methods were calculated respectively to evaluate the clinical application value of mNGS. Results: Among 161 patients with suspected pulmonary infection，113 cases were finally confirmed as pulmonary infection. Among the 161 patients enrolled，the sensitivity and negative predictive value of mNGS were improved compared with routine culture and nucleic acid detection of respiratory pathogens，and the difference was statistically signifi- cant(P＜0. 001) ．Although the specificity of mNGS was higher than that of respiratory pathogen nucleic acid de- tection，the difference was not statistically significant．The positive predictive value of mNGS was the highest，and was higher than that of respiratory pathogen nucleic acid detection，but had no statistical significance compared with conventional culture． Conclusion The sensitivity of mNGS in the diagnosis of pathogenic microorganisms in pul- monary infection is higher than that of conventional culture and nucleic acid detection of respiratory pathogens， which reduces the false negative rate of diagnosis and has a better comprehensive evaluation ; conventional culture detection has low sensitivity，but high specificity ; respiratory pathogen nucleic acid detection compared with con- ventional culture，the sensitivity is improved，but the specificity decreased.

Excessive and persistent inflammatory responses are a potential pathological condition that can lead to diseases of various systems, including nervous, respiratory, digestive, circulatory, and endocrine systems. Cannabinoid type 2 receptor(CB2R) belongs to the G protein-coupled receptor family and is widely distributed in immune cells, peripheral tissues, and the central nervous system. It plays a role in inflammatory responses under various pathological conditions. The down-regulation of CB2R activity is an important marker of inflammation and and CB2R modulators have been shown to have anti-inflammatory effects. This study explored the relationship between CB2R and inflammatory responses, delved into its regulatory mechanisms in inflammatory diseases, and summarized the research progress on CB2R modulators from plants other than cannabis, including plant extracts and monomeric compounds, in exerting anti-inflammatory effects. The aim is to provide new insights into the prevention and treatment of inflammatory diseases.
Cannabinoid Receptor Modulators/pharmacology* ; Cannabinoid Receptor Agonists/pharmacology* ; Receptors, Cannabinoid ; Cannabinoids/pharmacology* ; Anti-Inflammatory Agents/pharmacology*

Objective: To investigate the clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Methods: A retrospective observational study was conducted. From May 2018 to February 2020, 8 patients with pressure ulcers on the ischial tuberosity combined with chronic osteomyelitis who met the inclusion criteria were admitted to Fuyang Minsheng Hospital, including 5 males and 3 females, aged 38-69 years, with unilateral lesions in 6 patients and bilateral lesions in 2 patients. According to the anatomical classification of Cierny-Mader osteomyelitis, there were 6 patients (7 sides) with focal type, and 2 patients (3 sides) with diffuse type. The wound areas were 3 cm×2 cm to 12 cm×9 cm on admission. The pressure ulcer and chronic osteomyelitis lesions were completely removed by en bloc resection and debridement. The chronic infectious lesions were transformed into sterile incisions like fresh wounds by one surgical procedure, and the gluteus maximus muscle flaps with areas of 10 cm×6 cm to 15 cm×9 cm were excised to transfer and fill the ineffective cavity. The wounds of 5 patients were sutured directly, and the wounds of 3 patients were closed by local flap transfer. The intraoperative blood loss volume and blood transfusion, and length of hospital stay of patients were recorded. The incision healing and flap survival of patients were observed after operation. The recurrence of pressure ulcer and osteomyelitis, the appearance of the affected area, and the secondary dysfunction and deformity of the muscle flap donor site of patients were observed during followed up. Results: The intraoperative blood loss volume of the 8 patients was 220 to 900 (430±150) mL; 5 patients received intraoperative blood transfusion, of which 2 patients received 3 U suspended red blood cells and 3 patients received 2 U suspended red blood cells. The length of hospital stay was 18 to 29 (23.5±2.0) d for the 8 patients. In this group of patients, the incisions of 7 patients healed, while in one case, the incision suture was torn off during turning over and healed after secondary suture. The flaps survived well in 3 patients who underwent local flap transfer. During the follow-up period of 6-20 months, no recurrence of pressure ulcer or osteomyelitis occurred in 8 patients, the affected part had skin with good texture, mild pigmentation, and no sinus tract formation, and no secondary dysfunction or deformity occurred in the donor site. Conclusions: The en bloc resection and debridement combined with gluteus maximus muscle flap has good clinical effects on ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Neither pressure ulcer nor osteomyelitis recurs post operation. The skin texture and appearance of the affected area are good, and the donor site has no secondary dysfunction or deformity.
Blood Loss, Surgical ; Debridement ; Female ; Humans ; Male ; Muscles/surgery* ; Osteomyelitis/surgery* ; Perforator Flap ; Pressure Ulcer/surgery* ; Reconstructive Surgical Procedures ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Treatment Outcome

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline

Aim To evaluate the effects of Rutaecarpine(Rut)on the expression of SIRT1 and the senescence of vascular smooth muscle cells(VSMCs)induced by angiotensin Ⅱ.Methods VSMC senescencewas induced by exposure to AngⅡ(1 μmol·L-1)for 72 h.VSMCs were treated with different concentrations of Rut(0.3, 1, 3 μmol·L-1).TRPV1 competitive antagonist CAPZ(10 μmol·L-1)and AMPK inhibitor Compound C(1 μmol·L-1)were used to explore whether TRPV1/AMPK mediated the protective effect of Rut.The quantity of senescent cells were determined by senescence-associated SA-β-Gal staining, and the intracellular ROS level was measured by(DCFH-DA)fluorescent probe.The migration ability of VSMCs was evaluated by Wound-healing assay combined with Transwell assay.The protein level of longevity protein SIRT1 and senescence-related proteins p53, p21 and AMPK phosphorylation level were detected by Western blot.Results Rut significantly inhibited Ang Ⅱ-induced VSMC senescence and ROS production and prevented VSMCs migration.Preprocessing of TRPV1 antagonist CAPZ could abolish the protective effect of Rut.Ang Ⅱ inhibited the expression of longevity protein SIRT1.Rut recovered SIRT1 expression in a dose-dependent manner, while prevented the up-regulation of senescence-related proteins p53 and p21.Ang Ⅱ inhibited AMPK phosphorylation, pre-treatment with Rut restored AMPK phosphorylation level.CAPZ and Compound C eliminated the up-regulating function of Rut on SIRT1 expression.Conclusions Rut up-regulates the expression of SIRT1 and prevents the senescence and migration of VSMCs induced by Angiotensin Ⅱ, which is related to activation of the TRPV1/AMPK signaling pathway.

Objective: To explore the hemorrhagic transformation(HT) and its effect on prognosis in patients with acute ischemic stroke(AIS) after mechanical thrombectomy(MT). Methods: A total of 114 patients with AIS received MT were enrolled. The modified Rankin Scale was used to evaluate the clinical outcome at 90 days of onset(0-2 points were good prognosis; 3-6 points were poor prognosis). The patients were divided into HT group(n=25) and non-HT group(n=89) according to their HT conditions. Binomial Logistic regression analysis was performed to determine the vascular risk factors of HT after MT and the effect of HT on prognosis. Results: Among 114 patients, there were 25 cases of HT and 89 cases of non HT. The proportion of patients with diabetes in HT group was significantly higher than that in non-HT group. The NIHSS score of HT group at discharge was significantly higher than that in non-HT group. The proportion with good prognosis at 90 days in HT group was significantly lower than that in non-HT group(allP<0.05). Binomial Logistic regression analysis showed that diabetes, high levels of cholesterol and smoking were the major vascular risk factors for HT after thrombectomy(allP<0.05). HT was an important factor affecting the poor prognosis after arterial thrombectomy(P=0.026). Conclusion Diabetes, high levels of cholesterol and smoking are the main risk factors of HT after MT for AIS. HT is an independent risk factor for poor prognosis after MT.