OBJECTIVES: To investigate the effect of Haematococcus pluvialis (HP) on bleomycin (BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts (HFL1). METHODS: Thirty male C57BL/6 mice were randomly divided into control group, BLM-induced pulmonary fibrosis model group, low- and high-dose HP treatment groups (3 and 21 mg/kg, respectively), and 300 mg/kg pirfenidone (positive control) group. The effects of drug treatment for 21 days were assessed by examining respiratory function, lung histopathology, and expression of fibrosis markers in the lung tissues of the mouse models. In TGF-β1-induced HFL1 cell cultures, the effects of treatment with 120, 180 and 240 μg/mL HP or 1.85 μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240 μg/mL HP. RESULTS: HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice, evidenced by improved respiratory function, lung tissue morphology and structure, inflammatory infiltration, and collagen deposition and reduced expressions of fibrotic proteins. HP at the high dose produced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatment with 240 μg/mL HP significantly reduced the mRNA and protein expression levels of α-SMA and FN. Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis. CONCLUSIONS HP alleviates pulmonary fibrosis in both the mouse model and cell model, possibly as the result of the synergistic effects of its multiple active components.
Animals ; Pulmonary Fibrosis/chemically induced* ; Bleomycin/adverse effects* ; Mice, Inbred C57BL ; Male ; Mice ; Fibroblasts/drug effects* ; Lung/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Myofibroblasts/drug effects* ; Humans ; Pyridones

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To explore the surgical techniques and effects of transfer of the free chimeric functional thoracodorsal artery perforator flap (TDAPF) with latissimus dorsi in reconstruction of dynamic muscle and soft tissue defects in forearm.Methods:From January 2014 to December 2020, a total of 13 transfer surgery of free chimeric functional TDAPF with vascularised latissimus dorsi were performed in the Department of Hand Surgery, Plastic & Reconstructive Surgery, Ningbo Sixth Hospital, to reconstruct forearm composite defects. The patients were 12 males and 1 female with an average age of 33.2 years old. They all had open forearm injuries, with 5 in the left and 8 in the right. Removal of inactivated muscles, exploration and repair of blood vessels and nerves were performed in emergency surgery, and VSD were applied after the surgery. Phase II reconstructive surgery were completed within 4 to 12 days, with 7.5 days in average. The wounds and flaps sized were 9.0 cm×8.0 cm - 21.0 cm×11.0 cm and were 10.0 cm×9.0 cm - 22.0 cm×12.0 cm, respectively. The volume of transferred muscles ranged were 9.0 cm × 2.0 cm × 1.5 cm - 19.0 cm × 9.0 cm × 1.5 cm. Free chimeric functional muscular flaps were transferred to reconstruct the musculus flexor digitorum profundus in 4 patients, the musculus extensor digitorum communis in 8 patients, the musculus flexor carpi radialis in 3 patients, and the musculus flexor pollicis longus in 1 patient. Reconstruction of both of musculus flexor carpi radialis and musculus extensor digitorum communis with 2 functional sub-blocks of latissimus dorsi were performed in 3 patients. All donor sites were closed primarily. All patients were included in the postoperative follow-up to evaluate the appearance of flaps, range of motion of the digits, recovery of muscle strength and gripping power, at the outpatient clinics or through the telephone interview.Results:A total of 12 flaps survived uneventfully after reconstructive surgery. One flap developed a vascular crisis and it was rectified after surgical exploration. Postoperative follow-up ranged from 17 to 52 months, with a mean of 34.1 months. Appearances of limbs and flaps were good without obvious bulky, hyperpigmentation or scar contracture. Four patients with reconstructed musculus flexor digitorum profundus showed muscle strength recovery of M 4, with the fingertips measured lower than 2.0 cm from the centre of palm when clenching a fist, and the average gripping strength of the hand reached 27.5% (20%-35%) to the healthy side. Five patients with reconstructed musculus extensor digitorum communis showed muscle strength recovery of M 4, and there was no obvious limitation in fingers flexion and extension, with the average gripping strength of the hand reached 75.4% (65%-80%) to the healthy side. Of the 3 patients with reconstruction of both power muscles, the recovery of muscle strength of musculus flexor carpi radialis was at M 4 in all the 3 patients, and the musculus extensor digitorum communis was at M 4 in 1 and M 3 in 2 patients. However, the patient who received reconstruction of musculus flexor pollicis had no significant recovery in muscle strength. Conclusion:Transfer of free chimeric functional TDAPF combines the benefits of a perforator flap and a functional muscle transfer together. This surgical technique can effectively reconstruct damaged muscle groups in forearm and resulting in good hand movement. Additionally, it can also restore the aesthetic appearance of forearm, hence makes it an excellent option for complex wound coverage.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION This cell-based vascular graft is ready to undergo clinical trials for human patients.

BACKGROUND: Biliary tract carcinomas (BTCs) are relatively rare but lethal primary malignant tumors derived from the biliary tract system. The burden of BTCs varies according to sex, age, region, and country, but limited attention has been paid to the burden of BTCs. We sought to explore the up-to-date data from the Global Burden of Disease Study (GBD) and expand findings by accessing the demographic features of BTC disease burden. METHODS: Using the latest data from the GBD 2021, we evaluated and analyzed the distributions and patterns of BTC disease burden in various age groups, sexes, regions, and countries. RESULTS: The number of incident cases, deaths, and disability-adjusted life-years (DALYs) tended to increase and peaked at 216,770 (95% uncertainty interval [UI]: 181,890-245,240), 171,960 (95% UI: 142,350-194,240), and 3,732,100 (95% UI: 3,102,900-4,317,000) person-years, respectively, in 2021. However, the average global age-standardized rates (ASRs) of incident cases, deaths, and DALYs shrunk by -11.46% (95% UI: -21.91 to 3.35%), -24.09% (95% UI: -33.19 to 16.88%), and -26.25% (95% UI: -35.53 to 18.36%), respectively, from 1990 to 2021. Meanwhile, the male/female ratio (male per 100 female) of incidence, deaths, and DALYs changed from 76.40, 75.41, and 74.72 to 86.89, 79.11, and 82.29, respectively. In 2021, the highest number of incident cases, deaths, and DALYs occurred in East Asia. The top three highest incidences, deaths, and DALYs were observed in China, India, and Japan, and the highest ASRs were observed in Chile in 2021. Analysis of the Human Development Index along with disease burden estimates of BTCs also suggests that the burden of the disease is related to the level of comprehensive development of the society. CONCLUSION This study provided a comprehensive comparison of differences in the burden of disease across populations and over time, and further presented evidence concerning the formulation of prevention and control policies and etiologic studies for BTCs and proposed logical hypotheses to investigate.
Humans ; Global Burden of Disease ; Biliary Tract Neoplasms/epidemiology* ; Male ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Incidence ; Aged, 80 and over ; Quality-Adjusted Life Years ; Cost of Illness

Metastases account for the overwhelming majority of cancer-associated deaths. The dissemination of cancer cells from the primary tumor to distant organs involves a complex process known as the invasion-metastasis cascade. The underlying biological mechanisms of metastasis, however, remain largely elusive. Recently, the discovery and characterization of non-coding RNAs (ncRNAs) have revealed the diversity of their regulatory roles, especially as key contributors throughout the metastatic cascade. Here, we review recent progress in how three major types of ncRNAs (microRNAs, long non-coding RNAs, and circular RNAs) are involved in the multistep procedure of metastasis. We further examine interactions among the three ncRNAs as well as current progress in their regulatory mechanisms. We also propose the prevention of metastasis in the early stages of cancer progression and discuss current translational studies using ncRNAs as targets for metastasis diagnosis and treatments. These studies provide insights into developing more effective strategies to target metastatic relapse.
Gene Expression Regulation, Neoplastic/genetics* ; RNA, Untranslated/genetics* ; MicroRNAs ; RNA, Long Noncoding ; RNA, Circular/genetics*

Objective:To evaluate the feasibility of using positive anti-M-type phospholipase A 2 receptor(PLA 2R)antibody detection as a surrogate for renal biopsy in the diagnosis of idiopathic membranous nephropathy(IMN)in elderly Chinese. Methods:From June 2021 to March 2022, clinicopathological data of ninety-six elderly patients(≥60 years old)with positive anti-PLA 2R antibody detection(ELISA≥14 RU/ml), complete renal pathology records, and the exclusion of secondary disease and diabetes mellitus were collected from the Department of Nephrology, The First Affiliated Hospital of Zhengzhou University.Patients were divided into high eGFR group(≥60 ml·min -1·1.73 m -2)and low eGFR group(<60 ml·min -1·1.73 m -2), and the data were analyzed retrospectively. Results:Of the 96 patients, 95(99.0%)had IMN(1 in stage Ⅰ, 59 in stage Ⅱ, 34 in stage Ⅲ, and 1 in stage Ⅳ), and 1(1.0%)had atypical membranous nephropathy(AMN).For the IMN patients, 81(85.3%)had high eGFR and most IMN patients(66.7%)were in stage Ⅱ, with 10(12.3%)showing additional pathological findings, including mild mesangial proliferative IgA nephropathy(2 cases)and subacute tubulointerstitial nephropathy(2 cases).There were 14 patients(14.7%)with low eGFR, and most of them(57.1%)had stage Ⅲ IMN, with 10(71.4%)showing additional pathological findings.This percentage was higher than that in the high eGFR group( χ2=21.642, P<0.05).The most common additional pathological findings were acute tubular injury(4 cases)and ischemic kidney injury(2 cases). Conclusions:Positive anti-PLA 2R antibody detection is highly predictive of IMN in elderly Chinese patients, but it often co-exists with other pathological entities.The advantages of renal biopsy in detecting other pathological conditions and the risks associated with the procedure should be evaluated.

Ischemic-type biliary lesion (ITBL) refers to biliary tract injury caused by insufficient blood supply of hepatic artery, which is one of the main factors affecting the long-term survival and quality of life of liver transplant recipients. The incidence of ITBL is associated with cold and warm ischemia, acute and chronic rejection, cytomegalovirus infection and the bile effect, etc. The occurrence of ITBL is a complicated process involving with multiple factors and steps. The therapeutic option of ITBL is extremely limited. A large proportion of ITBL patients should undergo repeated liver transplantation. ITBL has become one of the most critical factors preventing further advancement of liver transplantation. Hence, it is of significance to strengthen prevention and explore more effective modalities. Recent studies have found that toxic injury of bile salts plays a central role in ITBL. Active regulation of bile components, regulation of bile acid-related receptor expression and blockage or activation of bile acid-related signaling pathways probably have potentials in the prevention and treatment of ITBL. In this article, the cytotoxicity of bile salts and the mechanism of bicarbonate umbrella in the incidence and progression of ITBL after liver transplantation were reviewed, aiming to provide reference for the diagnosis and treatment of ITBL.

Background The contracted family doctor services are the embodiment of the implementation of the new medical reform policy, and the transformation of the grass-roots health service mode. Studies have proved that the occupational stress in medical staff was at a high level. The enhancement of professional identity will contribute to strengthen team building，alleviate job burnout, and reduce turnover intention of family doctors. Objective To investigate the current situation of occupational identity among family doctor teams in Chengdu, to examine potential influencing factors of occupational identity, and to provide a reference for promoting career development and team building of family doctor teams. Methods Multi-stage random cluster sampling was adopted to enroll study participants form 46 primary healthcare centers where family doctor contract services were implemented among 23 districts and counties in Chengdu between March 4 and 26, 2021. A total of 2 681 family doctors participated in this survey. A self-reported survey was conducted to collect participants' demographic and occupational data. The Effort-Reward Imbalance (ERI）questionnaire was implemented to assess occupational stress. The Professional Identity Scale was used to appraise occupational identity. Results A total of 2 327 valid questionnaires were collected, with a valid recovery rate of 86.80%, involving 1 715 females (73.7%) and 612 males (26.3%), with dominant age groups of 26−35 years (43.3%) and 36−45 years (30.4%), a high proportion of being married (82.8%), having college (36.0%) and undergraduate (47.3%) education, a high proportion of primary titles (66.0%) and informal work contract (66.1%). About 88.7% of family doctor team workers reported occupational stress. The average score of occupational identity was (3.68±0.62) points. There were significant differences in occupational identity scores among different professional title, work contract, working years in medical institutions, income, and effort/reward ratio (EER) groups (P < 0.05). ERR was negatively correlated with occupational identity (r_s=−0.495, P<0.05）. The multiple regression model showed that occupational identity score in the non-staffed participants was lower than the score in the staffed ones (OR=0.429, 95%CI: 0.299−0.825). The occupational identity score in the participants having associate senior title or above was higher than in without professional title (OR=1.424, 95%CI: 1.194−2.328). The longer the working years, the higher the occupational identity score among the participants. The score of the more than 20 working years group was 1.820 times that of the less than 5 working years group (95%CI: 1.342−2.543). The higher the income, the higher the occupational identity score. The score of the 9001−12000 yuan per month group was 1.977 times that of the 1000−3000 yuan per month group (95%CI: 0.811−9.696) , and the score of the more than 12000 yuan per month group was 2.283 times that of the 1000−3000 yuan per month group (95%CI: 1.199−10.267）. Conclusion The family doctor team workers generally report occupational stress, and their occupational identity is at a medium level in Chengdu. Relevant managers should implement intervention measures against the main influencing factors to reduce their work tension and improve their occupational identity.