Objective To explore the effect of a phased rehabilitation training programme to relieve shoulder dys-function in patients after neck dissection and to provide effective solutions for postoperative shoulder joint function recov-ery of patients.Methods This study has been reviewed and approved by the Ethics Committee,and informed consent has been obtained from patients.A phased rehabilitaiton training programme for the shoulder after neck dessection was developed through literature review and discussion,and 70 eligible patients from Hospital of Stomatology,Sun Yat-sen University from December 2020 to April 2021 were selected and randomly divided into the test group and control group(35 patients in each group).The control group underwent motor rehabilitation training from 6 weeks postoperative to 1 year after surgery,such as shoulder mobility and coordination training and small range of motion training of the neck,while the test group took part in a rehabilitation training program that included familiarization maneuver training,protective rehabilitation,exercise rehabilitation,and resistance training in the following four stages:preoperative,postop-erative general anesthesia and awake until the removal of stitches,the removal of stitches until 6 weeks after surgery,and 6 weeks after surgery until 1 year after surgery.The frequency of training in both groups was at least 3 days per week,and the length of each training session was 10-15 min.The intensity of exercise was 2-3 points on the Borg Conscious Ex-ercise Intensity Scale(i.e.,mild-to-moderate tachypnea or fatigue).The neck dissection injury index(NDII)was used to evaluate the quality of life related to shoulder joint function at four time points:preoperative,postoperative 3 months,postoperative 6 months,and postoperative 12 months.The higher the score,the better the quality of life.Results 28 cases in the test group and 32 cases in the control group completed a one-year follow-up.At 3 and 6 months postopera-tive,the NDII of the test group was significantly higher than that of the control group[3 months postoperative:test group(93.48±9.36)vs.control group(80.00±11.34)(P＜0.001),6 months postoperative:test group(98.21±4.76)vs.control group(90.70±9.12)(P＜0.001)];12 months after surgery,the NDII of the test group(97.23±4.88)was still higher than that of the control group(96.33±4.49),but the difference was not statistically significant(P=0.458).The difference in NDII scores among subjects at 3,6,and 12 months after surgery was statistically significant in each group(P＜0.001).Conclusion The application of the phased rehabilitation training method in neck dissection patients has a feasibility and could improve the quality of life of patients'shoulder joint function within 6 months after surgery.

Objective To study the role of microRNA(miR)-483-3p in reducing myocardial fibrosis in rats,and explore the relationship between its mechanism and autophagy.Methods A total of 24 male SD rats were randomly divided into sham operation group,model group,blank transfec-tion group and high expression group,with 6 rats in each group.The blank transfection group and the high-expression group were pretreated with a single injection of adeno-associated virus(AAV)-blank transfection and AAV-miR-483-3p(5×1011 vg)in the tail vein,respectively.In 14 d later,the sham group was injected with 2.5 ml/(kg·d)normal saline for 14 d,and rat model of myocardial fibrosis was established by 2 mg/ml isoproterenol[2.5 ml/(kg·d)]injection through tail vein for 14 consecutive days.Myocardial pathological damage,severity of myocardial fibrosis,and expression levels of collagen-Ⅰ,microtubule-associated protein light chain 3(LC3),autoph-agy-related protein 5(Atg5)and autophagy degradation substrate(P62)in cardiomyocytes were evaluated and measured.Results Compared with the sham operation group,the model group had obviously larger myocardial fibrosis area,higher positive expression of Collagen-Ⅰ,and increased protein levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ,and decreased expression level of P62 protein(P＜0.05).The myocardial fibrosis area,positive expression of Collagen-Ⅰ,the expression levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ protein[(13.64±1.51)％vs(27.47±1.55)％,(13.48±3.07)％vs(30.91±2.45)％,0.98±0.17 vs 1.24±0.28,0.66±0.05 vs 1.26±0.09,P＜0.05]were significant-ly decreased,and the expression level of P62 was notably increased(0.91±0.11 vs 0.74±0.06,P＜0.05)in the high expression group than the model group.Conclusion MiR-483-3p attenuates myocardial fibrosis in rats,and the mechanism may be related to the inhibition of cardiomyocyte autophagy.

Objective To explore the therapeutic effect of bicyclol(BIC)on rat model of myocardial fibrosis and its possible mechanism.Methods Twenty-four SPF male SD rats were randomly di-vided into sham group,model group,low-and high-dose groups,with 6 rats in each group.Except for the sham group,all other groups were injected with 5 mg/(kg·d)isoproterenol by tail vein to establish myocardial fibrosis model,and the low-and high-dose groups were administered by ga-vage with 100 and 200 mg/(kg·d)BIC,respectively for 14 consecutive days.HE staining and Masson staining were used respectively to observe the severity of myocardial injury and fibrosis.Western blot assay was employed to detect the protein expression of Collagen Ⅰ,Collagen Ⅲ,al-pha smooth muscle actin(α-SMA),methyltransferase-like protein 3(METTL3),α-ketoglutarate-dependent dioxygenase AlkB homolog 5(ALKBH5)and YTH domain family protein 1(YTHDF1)in rat myocardium.Results Compared with the sham group,myocardial cell necrosis and myocardial fibrosis were significantly more serious in the model group.Low-and high-dose BIC treatment reduced myocardial cell rupture and necrosis and myocardial fibrosis when com-pared with the model group.The expression levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,METTL3 and YTHDF1(P＜0.05)were significantly higher,and that of ALKBH5(0.58±0.02 vs 0.88±0.07,P＜0.05)was notably lower in the myocardial tissues of the model group than the sham group.While,both doses of BIC treatment significantly reversed above changes in protein levels(P＜0.05).Conclusion BIC can effectively alleviate myocardial structural damage and interstitial collagen deposition in rats with isoproterenol-induced myocardial fibrosis,and its mechanism may be related to m6A methylation modification.

Circadian rhythm disorders are closely related to metabolic diseases， which can cause non-alcoholic fatty liver disease （NAFLD） by directly acting on the liver or indirectly affecting the liver through the liver-brain axis and intestinal flora. The rhythms of yin and yang， ying （营） and wei （卫）， twelve hours and four seasons in traditional Chinese medicine （TCM） chronomedicine are similar to the connotations of modern biological rhythms. From the perspective of chronomedicine of TCM， the incidence of NAFLD is closely related to the abnormality of the daily rhythm of the waxing and waning of yin and yang， the daily rhythm of the circulation of ying and wei， the rhythm of twelve hours and four seasons. Through analyzing the rhythms related to the occurrence， development and prognosis of NAFLD， it is helpful to enhance the understanding of NAFLD in relation to time， so as to better guide the clinical diagnosis and treatment.

Objective:To analyze the imaging manifestations of 18F-fluorodeoxyglucose positron emission tomography/computed tomography(18F-FDG PET/CT)in the patients with pleural and peritoneal mesothelioma,and to enhance the diagnostic accuracy for this disease.Methods:A retrospective analysis was conducted on the 18F-FDG PET/CT imaging and immunohistochemical results of 22 patients confirmed pleural and peritoneal mesothelioma(21 malignant and 1 benign)by pathology.The imaging features and glucose metabolism characteristics were summarized.Results:The majority of the patients with malignant pleural mesothelioma presented with unilateral pleural diffuse thickening accompanied by increased radiotracer uptake,and the thicknesses were ranged from 1.0 to 10.6 cm and the average semi-quantitative maximum standard uptake value(SUVmax)was 10.1.Over half of these patients also had a small amount of pleural effusion.The patients with malignant peritoneal mesothelioma mostly showed diffuse thickening of the peritoneum,omentum,and mesentery with increased radiotracer uptake,and the thicknesses were from 1.2 to 6.6 cm and the average SUVmax was 8.4,and over half of these patients had a significant amount of abdominal ascites.Besides the primary sites,nodular,striated,and mass-like abnormal radiotracer uptakes were observed in other metastatic sites in 17 cases of malignant mesothelioma,suggesting metastasis,and the average SUVmax was 7.4,predominantly surrounding lymph node metastasis.Bone and muscle metastases were visible in the patients with malignant pleural mesothelioma,while no such metastasis were seen in those with malignant peritoneal mesothelioma.One patient with benign pleural mesothelioma presented with bilateral pleural diffuse thickening approximately 3.5 cm thick,without significant abnormal radiotracer uptake and with a minor pleural effusion.Conclusion:The 18F-FDG PET/CT imaging manifestations of pleural and peritoneal mesothelioma exhibit the distinctive characteristics.The mode and thickness of pleural and peritoneal thickening,the presence and degree of 18F-fluorodeoxyglucose uptake,can preliminarily differentiate between benign and malignant mesothelioma,thus providing valuable references for the early clinical diagnosis of mesothelioma.PET/CT based on whole-body imaging can determine whether there are other sites of metastasis,which is helpful for clinical staging.

Objective To study the changes of blood glutathione peroxidase (GSH-px),superoxide dis-mutase (SOD),malondialdehyde (MDA) and pathological tissues in the rat contrast-induced nephropathy (CIN) model,and to determine the role of oxidation mechanism in CIN.Methods A total of 40 adult male SD rats were selected and divided into three big groups and five small groups.After constructing the model,six rats with good status were taken from each group for conducting the experiment.The serum GSH-px,SOD and MDA levels were measured,the renal tissue biopsy was performed and the morphological changes of kid-ney cells were compared.Results There was no statistically significant difference in the baseline data among the blank control group,the control group and the experimental group (P>0.05).There was no statistically significant difference in serum GSH-px,SOD and MDA levels before model construction,at 24,48 h after model construction between the blank control group and the control group (P>0.05).There were statistical-ly significant differences in serum GSH-px,SOD and MDA levels of the experimental group between before model construction and after model construction (P<0.05).There was no statistically significant difference in serum GSH-px,SOD and MDA level in the experimental group between at 24 h after modelling and 48 h af-ter modeling (P>0.05).There was no statistically significant difference in serum GSH-px,SOD and MDA levels at 24 h after modeling among the three groups (P>0.05).There were statistically significant differ-ences in serum GSH-px,SOD and MDA levels at 48 h after modeling among the three groups and their pairs (P<0.05).The pathological sections of the blank control group and control group showed no obvious abnor-mal changes in glomeruli,renal tubule and renal interstitium.Renal interstitial fibrosis and inflammatory cell infiltration were seen after 24 h in the experimental group,but there was no obvious change in the renal tu-bules.After 48 h,moderate focal-like atrophy of renal tubules,epithelial cell granule degeneration and vacuolar changes were obviously seen.Conclusion The oxidative stress mechanism plays a role in CIN.The contrast a-gent acute renal injury mainly acts on the renal tubules and renal interstitium,and there is no obvious damage to the glomeruli.

Objective:To investigate the clinicopathological and molecular genetic characteristics of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) with myxoid-like morphology, and to distinguish them from myxofibrosarcoma (MFS) with similar morphology.Methods:Twenty-nine cases of myxoid-like liposarcoma and 5 cases of MFS were collected from Henan Provincial People′s Hospital, Zhengzhou, China and the First Medical Center of PLA General Hospital, Beijing, China from January 2015 to March 2023. Relevant markers were detected using immunohistochemistry and fluorescence in situ hybridization (FISH). The literature was also reviewed.Results:There were 24 males and 10 females, with ages ranging from 41 to 73 years. The tumor sites included retroperitoneum ( n=17), abdomen ( n=9), lower limbs ( n=5), scrotum ( n=1), upper limb ( n=1) and axilla ( n=1). WDLPS was commonly seen as lipomatoid type (12 cases), while the dedifferentiated components of DDLPS included low-grade (13 cases) and high-grade (2 cases) morphology, with low-high grade myxofibrosarcoma, dermatofibrosarcoma protuberans, and low-grade fibrosarcoma structures. Twenty-nine liposarcomas had various proportions of myxoid-like morphology, while 16 showed various degrees of tumor necrosis. The myxoid-like component showed myxoid pleomorphic liposarcoma (MLPS)-like morphology, lobulated growth, characteristic slender, ramified capillary network,"chicken claw-like"morphology, mucus-rich stroma and lung edema-like morphology. Tumor cells were spindle and oval, with many variable vacuolar lipoblasts. MDM2 gene amplification was detected using FISH and present in all tested cases (29/29). DDIT3 break-apart mutation was not detected, but its cluster amplification was present (24/29). Among the MFS cases, one showed cluster amplification (1/5), but no cases showed break-apart or amplification of MDM2 gene. Conclusions:WDLPS/DDLPS with myxoid-like morphology is most commonly seen in the retroperitoneum and abdominal cavity and mostly harbors DDIT3 break-apart probe amplification, while this amplification is not specific to liposarcoma. For core biopsy specimens or very rare tumors in the limbs, when histology has mucinous stroma and MLPS-like morphology, misdiagnosis of MLPS or other non-lipomatous neoplasms with myxoid morphology should be avoided.

With good prognosis of differentiated thyroid cancer (DTC), the 10-year survival rate of DTC patients is more than 90%. As a kind of radiation exposure, radioactive iodine (RAI) treatment has the potential to induce malignancies. Based on this view, whether RAI treatment will increase the risk of secondary primary malignancy (SPM) still has a lot of controversy. This review summarizes current situation of related researches, and also summarizes the limitations of the current researches and the problems to be solved in the future research. In this review, it is believed that RAI treatment does not increase the overall risk of SPM in postoperative-DTC patients.

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

Objective:To investigate the clinicopathological features and genevariation of sporadic arteriovenous malformation (AVM) in soft tissue.Methods:Eighty cases of soft tissue sporadic AVM diagnosed in Henan Provincial People′s Hospital from January 2017 to March 2022, were retrospectively collected. The relevant indicators were detected by immunohistochemistry and fluorescent quantitative PCR, and the relevant literature was reviewed.Results:There were 42 males and 38 females patients, aged from 4 to 71 years, with a mean age of 26 years.The sites of the disease included head and neck (34 cases), limbs (24 upper limbs, 17 lower limbs) and trunk (5 cases). The main clinical manifestations were characteristic pulsation, tremor, temperature rise, local pain, ulcer or repeated bleeding, and heart failure in severe cases due to long-term hemodynamic abnormalities.Color Doppler ultrasound (CDFI) can detect the high flow characteristics of AVM.Multiple cavitary vascular shadows were seen on MRI. Microscopically, the pathological tissue involved the skin appendages, deep fat and muscle tissue, in which abnormal vascular proliferation was seen, mostly scattered, the lumen was irregularly expanded, the wall thickness was different, but most of them were thick, the vascular wall was glassy and myxoid, inflammatory cell infiltration, bleeding, thrombosis and organization were visible, and calcification was rare.Clustered proliferative muscular small vessels were found around the abnormal blood vessels.No vascular endothelial cell proliferation was found in the blood vessels of the lesion. Immunohistochemistry showed that vascular endothelial cells expressed CD31, CD34 and ERG, and muscle fibers and smooth muscle tissues in the wall expressed SMA.Elastic fiber staining showed incomplete elastic layer in the wall of the malformed artery.PIK3CA gene was detected in 15 cases, and 1 case (1/15) had mutation (mutation rate 6.7%). All cases underwent surgical resection, 73 cases were followed up for 3 months to 5 years, and 15 cases recurred.Conclusions:Sporadic AVM in soft tissue is a typical lesion of vascular malformation with high flow velocity. There are abnormal arteries and clusters of proliferating small vessels.Because of the significant difference in clinical manifestation, treatment and prognosis, pathological diagnosis should be distinguished from congenital hemangioma, intramuscular hemangioma capillary type, PTEN soft tissue hamartoma and common venous malformation.Very few cases may involve PIK3CA gene mutation, suggesting that there may be abnormal PI3K signal pathway in AVM and may participate in the occurrence and development of the disease. AVM has a high recurrence rate and needs long-term follow-up.