Objective:Anterior cruciate ligament injury is the most common type of knee joint ligament injury.Anterior cruciate ligament reconstruction has a high failure rate,with bone tunnel abnormalities as the most significant factor in these failures.Digital orthopedic technology can effectively develop implementation plans for the revision,thus increasing the success rate.This study aims to develop a surgical plan for anterior cruciate ligament revision by employing multiplanar reconstruction(MPR)for measuring bone tunnel position and diameter,and simulating bone tunnel creation via 3D printing preoperatively. Methods:A total of 12 patients who underwent anterior cruciate ligament revision at the Third Xiangya Hospital of Central South University between 2014 and 2021 were retrospectively studied.The data included patient demographics,preoperative formulated knee joint 3D printing models,and preoperative knee CT scans.The study measured the bone tunnel's diameter and position to guide the establishment of revision bone tunnels during surgery,reassessed the postoperative bone tunnels,and evaluated knee joint functional scores[including International Knee Documentation Committee Knee Evaluation Form(IKDC)score,Lysholm score,and Tegner exercise level score]. Results:Preoperative measurements revealed suboptimal femoral tunnels positions in 4 patients and tibial tunnels positions in 2 patients.MPR and 3D printing technology were used to guide the establishment of a new bone canal during surgery,and postoperative measurements were satisfactory for all patients.Preoperative measurements demonstrated the interclass correlation coefficient for femoral tunnels and tibial tunnels diameters were 0.843(P<0.05)and 0.889(P<0.001),respectively.Meanwhile,the intraclass correlation coefficient were 0.811(P<0.05)and 0.784(P<0.05),respectively.The intraoperative diameter of femoral and tibial tunnels showed excellent correlation with postoperative CT measurements,with intraclass correlation coefficient values of 0.995(P<0.001)and 0.987(P<0.001),respectively.All bone tunnel positions were within the normal range.At the final follow-up,knee joint function scores in all 12 patients improved significantly compared to pre-surgery(P<0.001),and the reoperation rate was zero. Conclusion:MPR and 3D printing technology can accurately measure the parameters of reconstructed anterior cruciate ligament bone tunnels.Personalized revision plans for patients with reconstruction failure enhances the success rate of revision surgery and improves patient prognosis.

Objective To study the inhibitory activities of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives against the entry of SARS-CoV-2 into host cells.Methods With pentacyclic triterpene saponin glycyrrhizic acid(a natural SARS-CoV-2 entry inhibitor)as the lead compound,a series of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives were designed and synthesized based on hypridization principle,and their inhibitory activities against virus entry were tested in SARS-CoV-2 pseudovirus-infected cells.The antiviral targets of the lead compound 1b was identified by pseudotyped SARS-CoV-2 infection assay and surface plasmon resonance(SPR)assay,and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of 1b on virus-cell membrane fusion.Molecular docking and single amino acid mutagenesis were carried out to analyze the effect of 1b on binding activitiy of S protein.Results The lead compound 1b showed significant inhibitory effect against Omicron pseudovirus with an EC50 value of 3.28μmol/L(P<0.05),and had broad-spectrum antiviral activity against other SARS-CoV-2 pseudovirus.Spike-dependent cell-cell fusion assay demonstrated an inhibitory effect of 1b against SARS-CoV-2 S protein-mediated cell-cell fusion.Molecular docking analysis predicted that the lead compound 1b could be well fitted into a cavity between the attachment(S1)and fusion(S2)subunits at the 3-fold axis,where it formed multiple hydrophobic interactions with Glu309,Ser305,Arg765 and Lys964 residues with a KD value of-8.6 kcal/mol.The compound 1b at 10,5,2.5 and 1.25 μmol/L showed a significantly reduced inhibitory activity against the pseudovirus with mutated Arg765,Lys964,Glu309 and Leu303(P<0.01).Conclusion 3-O-β-chacotriosyl glycyrrhetinic acid derivatives are capable of stabilizing spike protein in the pre-fusion step to interfere with the fusion of SARS-CoV-2 with host cell membrane,and can thus serve as potential novel small-molecule SARS-CoV-2 fusion inhibitors.

Objective To study the inhibitory activities of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives against the entry of SARS-CoV-2 into host cells.Methods With pentacyclic triterpene saponin glycyrrhizic acid(a natural SARS-CoV-2 entry inhibitor)as the lead compound,a series of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives were designed and synthesized based on hypridization principle,and their inhibitory activities against virus entry were tested in SARS-CoV-2 pseudovirus-infected cells.The antiviral targets of the lead compound 1b was identified by pseudotyped SARS-CoV-2 infection assay and surface plasmon resonance(SPR)assay,and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of 1b on virus-cell membrane fusion.Molecular docking and single amino acid mutagenesis were carried out to analyze the effect of 1b on binding activitiy of S protein.Results The lead compound 1b showed significant inhibitory effect against Omicron pseudovirus with an EC50 value of 3.28μmol/L(P<0.05),and had broad-spectrum antiviral activity against other SARS-CoV-2 pseudovirus.Spike-dependent cell-cell fusion assay demonstrated an inhibitory effect of 1b against SARS-CoV-2 S protein-mediated cell-cell fusion.Molecular docking analysis predicted that the lead compound 1b could be well fitted into a cavity between the attachment(S1)and fusion(S2)subunits at the 3-fold axis,where it formed multiple hydrophobic interactions with Glu309,Ser305,Arg765 and Lys964 residues with a KD value of-8.6 kcal/mol.The compound 1b at 10,5,2.5 and 1.25 μmol/L showed a significantly reduced inhibitory activity against the pseudovirus with mutated Arg765,Lys964,Glu309 and Leu303(P<0.01).Conclusion 3-O-β-chacotriosyl glycyrrhetinic acid derivatives are capable of stabilizing spike protein in the pre-fusion step to interfere with the fusion of SARS-CoV-2 with host cell membrane,and can thus serve as potential novel small-molecule SARS-CoV-2 fusion inhibitors.

{L-End}Objective To investigate the current status of long working hours of food-delivery workers from food-delivery platform, and analyze its impact on their health such as occupational stress, depressive symptoms, insomnia symptoms, fatigue accumulation, and life satisfaction. {L-End}Methods A total of 2 145 food-delivery workers from two food-delivery platforms in Guangzhou City were selected as the research subjects using convenience sampling method. The occupational stress, depressive symptoms, insomnia symptoms, fatigue accumulation, and life satisfaction were investigated using the Core Occupational Stress Scale, Patient Health Questionnaire-9 items, Self-sleep Management Questionnaire, Self-diagnosis Questionnaire of Fatigue Accumulation of Workers, and World Health Organization Five-item Well Being Index. {L-End}Results The median and the 25th and 75th percentiles of weekly working hours were 63 (49,77) hours. And 92.2% (1 978/2 145) of workers, who worked more than 40 hours per week, were long working hours workers. While 70.1% (1 504/2 145) workers, who worked 55 hours or more per week, were ultra-long working hours workers. The detection rate of occupational stress, depressive symptoms, insomnia symptoms, fatigue accumulation, and low life satisfaction was 30.1%, 27.5%, 34.7%, 40.8%, and 75.1%, respectively. The longer the weekly working hours of the research subjects, the higher the detection rate of occupational stress and fatigue accumulation (all P<0.01). The results of multivariate logistic regression analysis showed that ultra-long working hours (weekly working hours ≥55 hours) was the influencing factor of occupational stress and fatigue accumulation after excluding the influence of confounding factors among workers (all P<0.05). {L-End}Conclusion The food-delivery workers of food-delivery platforms generally work long hours. Ultra-long working hours is a risk factor for occupational stress and fatigue accumulation among these workers.

Intestinal fibrosis associated stricture is a common complication of inflammatory bowel disease usually requiring endoscopic or surgical intervention. Effective anti-fibrotic agents aiming to control or reverse intestinal fibrosis are still unavailable. Thus, clarifying the mechanism underpinning intestinal fibrosis is imperative. Fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) proteins at the injured sites. Multiple cellular types are implicated in fibrosis development. Among these cells, mesenchymal cells are major compartments that are activated and then enhance the production of ECM. Additionally, immune cells contribute to the persistent activation of mesenchymal cells and perpetuation of inflammation. Molecules are messengers of crosstalk between these cellular compartments. Although inflammation is necessary for fibrosis development, purely controlling intestinal inflammation cannot halt the development of fibrosis, suggesting that chronic inflammation is not the unique contributor to fibrogenesis. Several inflammation-independent mechanisms including gut microbiota, creeping fat, ECM interaction, and metabolic reprogramming are involved in the pathogenesis of fibrosis. In the past decades, substantial progress has been made in elucidating the cellular and molecular mechanisms of intestinal fibrosis. Here, we summarized new discoveries and advances of cellular components and major molecular mediators that are associated with intestinal fibrosis, aiming to provide a basis for exploring effective anti-fibrotic therapies in this field.

Objective To analyze histomorphometrical characteristics of the bone and bone marrow tissues of the lumbar vertebrae in rabbits with fluoride treatment,and its correlation with signal intensity of MRI.Methods Forty New Zealand albino rabbits aged three months old were randomly divided into fluoride exposure of 30 cases and control of 10 cases,male and female,half each.One hundred milligrams of sodium fluoride were added to the municipal water each liter (fluoride content 100 mg/L) as drinking waterto fluorine for 180 days.Twenty-four of 30 cases with fluoride exposure had complete data (male10 casesand female14 cases).The same municipal water was used as control drinking water (fluoride content ＜ 0.9 mg/L).Eight of 10 cases with control had complete data (male andfemale in half).Twenty-four cases with fluoride treatment and complete data were classified into sensitive and resistant type according to the MRI signal intensity of the lumbar vertebra.Histomorphometrics of the vertebra and its correlation with the MRI signal intensity,and sensitivity in early diagnosis of osteofluorosis and feasibility of susceptibility to osteofluorosis detected with MRI were analyzed.Results Theratios of trabecular bone volume (BV),hematopoietic cell volume (HV) and fluid volume (FV) in bone marrow tissue to total cavernous tissue volume (TT) in group with fluoride treatment were 18.3％±2.6％,45.2％±6.0％ and 10.4％±5.7％ respectively.These were 14.5％±2.8％,36.3％±7.3％ and 6.2％±2.1％ in control group respectively.These parameters in fluoride group were significantly increased compared to control group.The ratio 26.0％± 8.0％ of adipocyte volume (AV) to TV in fluoride group was significantly lower than that 43.3％±5.6％ in control group.Two of 24 cases with fluoride exposure (8.3％,2/24) were sensitive and the remaining 22 (91.7％,22/24) were in resistance.The valuesof BV/TT,HV/TV and FV/TV were considered to be sensitive,resistant and control from large to small,while AV/TV value were opposite.A comparison resuhs of signal intensity in MRI showed that vertebra T1WI contrast to noise ratio (CNR) in the sensitive was the minimum (3.0±0.8),followed by resistance (21.3±3.8) andmaximum in the control (28.3±3.1),but CNR of FsT2WIwas opposite.There were positive associations between T1WI and AV/TV,FV/TV and BV/TV,and between FsT2WI and FV/TV and BV/ TV.There were inverse associationsbetween FsT2WI and AV/TV.Theoptimal threshold value of the vertebra T1WI CNR was 23.2 or lessin early diagnosis of skeletal fluorosis,with sensitivity of 83.3％ and specificity of 100％.FsT2WI was 5.7 or more,with sensitivity of 45.8％ and specificity of 100％.Conclusion The pathogenesis of osteofluorosis is relative to changes in bone marrow microenvironment and cells number in bone marrow tissue,and is correlated to MRI signal intensity.

Objective To explore the effects of early intervention on brain injury in premature infants with neonate respiratory failure (NRF). Methods 151 premature infants in neonatal intensive care unit (NICU) who were diagnosed as NRF within 24 hours after birth in our hospital were studied. All of them accepted endotracheal intubation and mechanical ventilation, and were complicated with brain injury. According to their admission date and their parents' desire, these premature infants were divided into routine group (n=71) and intervention group (n=80). Both 2 groups received similar routine care, and the intervention group accepted touching, passive exercise and stimulation of hearing, vision and touch in addition. Active motor training and family intervention were also given to the intervention group after dis-charge. They were assessed with Neonatal Behavioral Neurological Assessment (NBNA) at the corrected age of 40 weeks, Infant Neurologi-cal International Battery (Infanib) at the corrected age of 3 and 6 months, mental development index (MDI) and psychomotor development index (PDI) at the corrected age of 6, 12 and 18 months, Gesell Development Schedules at the corrected age of 18 months. Results There was no significant difference in NBNA score between 2 groups at 40 weeks of gestational age (P>0.05). The percentage of normal ones with Infanib was higher in the intervention group than in the routine group at the age of 3 and 6 months (P<0.05). The MDI and PDI were signifi-cantly higher in the intervention group than in the routine group at the age of 6, 12 and 18 months (P<0.001). The scores of gross motor, fine motor, adaptation, language and social skills were significantly higher in the intervention group than in the routine group at the age of 18 months (P<0.001). The incidence of sequelae was lower in the intervention group (12.5%) than in the routine group (25.4%) (P<0.05). Con-clusion Early intervention can promote the intelligence and motor development, and improve the outcome of brain injury in the premature infants with NRF.

OBJECTIVETo compare the expressions of hypoxia-inducible factor 1 alpha(HIF-1α) and Semaphorin 4D(Sema4D) in colorectal carcinoma and normal colorectal tissues, and to investigate their correlation and clinical significance.

METHODSThe expressions of HIF-1α and Sema4D were examined in 86 cases of colorectal carcinoma and 52 normal colorectal tissues by SP immunohistochemical staining. Correlation between these two expressions and association of the expressions with clinicopathological characters and prognosis were analyzed.

RESULTSThe positive rates of HIF-1α and Sema4D protein in colorectal carcinoma tissues were significantly higher than those in normal colorectal tissues(58.1% vs. 7.7%, χ(2)=34.624, P<0.01; 60.5% vs. 11.5%, χ(2)=31.839, P<0.01). HIF-1α and Sema4D protein expressions were closely associated with colorectal carcinoma histological types(P=0.003, P=0.010), TNM staging (P=0.003, P=0.017) and lymphatic metastasis (P=0.003, P=0.020), and a significant correlation was observed between the expressions of HIF-1α and Sema4D protein (r=0.567, P<0.01). The 5-year overall survival rate was 37%. Univariate analysis showed that 5-year survival rates of patients with positive and negative HIF-1α protein expression were 24% and 56%(P=0.003), and those with positive and negative Sema4D protein expression were 23% and 59%(P=0.001). Multivariate Cox analysis showed that expression of Sema4D was an independent prognostic factor of colorectal cancer patients(P=0.026), while expression of HIF-1α was not(P=0.501).

CONCLUSIONCombined detection of HIF-1α and Sema4D has the potential to predict the development trend of colorectal carcinoma and prognosis of patients.

Antigens, CD ; metabolism ; Colorectal Neoplasms ; metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Semaphorins ; metabolism ; Survival Rate

BACKGROUNDHypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha (HIF-1α) plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D (Sema4D) also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages (TAMs) can increase the expression of HIF-1α and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-1α and the impact of biologic behavior in colon cancer cells.

METHODSImmunohistochemistry was used to analyze HIF-1α and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software (SPSS Inc., USA). Differences between two groups were analyzed with Student's t test.

RESULTSHIF-1α (58%) and Sema4D (60%) were expressed at a significantly higher level in tumors than in normal tissues (P < 0.01, for both). Furthermore, HIF-1α and Sema4D expression was significantly correlated with lymphatic metastasis, specific histological types and TNM stages (P < 0.05), but not with age and tumor size (P > 0.05). Sema4D expression was correlated with that of HIF-1α (r = 0.567, P < 0.01). TAMs markedly induced HIF-1α and Sema4D expression in colon cancer cells and subsequently increased their migration and invasion.

CONCLUSIONSHIF-1α and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-1α and Sema4D.

Adult ; Aged ; Antigens, CD ; genetics ; metabolism ; Cell Line, Tumor ; Colonic Neoplasms ; genetics ; metabolism ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Immunohistochemistry ; Macrophages ; immunology ; metabolism ; Male ; Middle Aged ; Neoplasm Metastasis ; genetics ; pathology ; Semaphorins ; genetics ; metabolism

Objective To compare the expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and Semaphorin 4D (Sema4D) in colorectal carcinoma and normal colorectal tissues, and to investigate their correlation and clinical significance. Methods The expressions of HIF-1α and Sema4D were examined in 86 cases of colorectal carcinoma and 52 normal colorectal tissues by SP immunohistochemical staining. Correlation between these two expressions and association of the expressions with clinicopathological characters and prognosis were analyzed. Results The positive rates of HIF-1α and Sema4D protein in colorectal carcinoma tissues were significantly higher than those in normal colorectal tissues (58.1% vs. 7.7%, χ2=34.624,P<0.01; 60.5% vs. 11.5%, χ2=31.839, P<0.01). HIF-1α and Sema4D protein expressions were closely associated with colorectal carcinoma histological types (P=0.003,P=0.010), TNM staging (P=0.003,P=0.017) and lymphatic metastasis (P=0.003,P=0.020), and a significant correlation was observed between the expressions of HIF-1α and Sema4D protein (r=0.567, P<0.01). The 5-year overall survival rate was 37%. Univariate analysis showed that 5-year survival rates of patients with positive and negative HIF-1α protein expression were 24% and 56%(P=0.003), and those with positive and negative Sema4D protein expression were 23% and 59%(P=0.001). Multivariate Cox analysis showed that expression of Sema4D was an independent prognostic factor of colorectal cancer patients(P=0.026), while expression of HIF-1α was not(P=0.501). Conclusion Combined detection of HIF-1α and Sema4D has the potential to predict the development trend of colorectal carcinoma and prognosis of patients.