Study on the correlation between early three-dimensional gait analysis and clinical efficacy after robot-assisted total knee arthroplasty.

PURPOSE: Robot-assisted technology is a forefront of surgical innovation that improves the accuracy of total knee arthroplasty (TKA). But whether the accuracy of surgery can improve the clinical efficacy still needs further research. The purpose of this study is to perform three-dimensional (3D) analysis in the early postoperative period of patients who received robot-assisted total knee arthroplasty (RATKA), and to study the trend of changes in gait parameters after RATKA and the correlation with the early clinical efficacy. METHODS: Patients who received RATKA in the Center of Joint Surgery, the First Hospital Affiliated to Army Military Medical University from October 2020 to January 2021 were included. The imaging parameters, i.e., hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, posterior condylar angle were measured 3 months post-TKA. The 3D gait analysis and clinical efficacy by Western Ontario Mac Master University Index (WOMAC) score were performed pre-TKA, 3 and 6 months post-TKA. The differences in spatiotemporal parameters of gait, kinetic parameters, and kinematic parameters of the operated limb and the contralateral limb were compared. The correlation between gait parameters and WOMAC scores was analyzed. Paired sample t-test and Wilcoxon rank-sum test were used to analyze the difference between groups, and Spearman correlation coefficient was used to analyze the correlation. RESULTS: There were 31 patients included in this study, and the imaging indexes showed that all of them returned to normal post-TKA. The WOMAC score at 3 months post-TKA was significantly lower than that pre-TKA, and there was no significant difference between at 3 and 6 months. The 3D gait analysis results showed that the double support time of the operated limb reduced at 3 and 6 months (all p < 0.05), the maximum extension and maximum external rotation of the knee joint increased at stance phase, and the maximum flexion angle, the range of motion and the maximum external rotation increased at swing phase. Compared with the preoperative data, there were significant improvements (all p < 0.05). Compared with the contralateral knee joint, the maximum external rotation of the knee joint at swing phase was smaller than that of the contralateral side, and the maximum flexion and extension moment was greater than that of the contralateral knee. The maximum external rotation moment of the joint was greater than that of the contralateral knee joint (p < 0.05). There was a negative correlation between the single support time pre-TKA and the WOMAC score at 3 months (p = 0.017), and the single support time at 3 months was negatively correlated with the WOMAC score at 6 months (p = 0.043). The cadence at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.031). The maximum knee extension at stance phase at 6 months was negatively correlated with the WOMAC score at 6 month (p = 0.048). The maximum external rotation at stance phase at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.024). CONCLUSION: The 3D gait analysis of RATKA patients is more sensitive than WOMAC score in evaluating the clinical efficacy. Trend of changes in gait parameters shows that the knee joint support, flexion and extension function, range of motion, external rotation and varus deformity moment of the patient were significantly improved at 3 months after surgery, and continued to 6 months after surgery. Compared with the contralateral knee, the gait parameters of the operated limb still has significant gaps in functionality, such as the external rotation and flexion and extension. The single support time, cadence, knee extension, and knee external rotation of the operated limb have a greater correlation with the postoperative WOMAC score. Postoperative rehabilitation exercises should be emphasized, which is of great value for improving the early efficacy of RATKA.

Animal models of chemotherapy-induced peripheral neuropathy: A machine-assisted systematic review and meta-analysis.

We report a systematic review and meta-analysis of research using animal models of chemotherapy-induced peripheral neuropathy (CIPN). We systematically searched 5 online databases in September 2012 and updated the search in November 2015 using machine learning and text mining to reduce the screening for inclusion workload and improve accuracy. For each comparison, we calculated a standardised mean difference (SMD) effect size, and then combined effects in a random-effects meta-analysis. We assessed the impact of study design factors and reporting of measures to reduce risks of bias. We present power analyses for the most frequently reported behavioural tests; 337 publications were included. Most studies (84%) used male animals only. The most frequently reported outcome measure was evoked limb withdrawal in response to mechanical monofilaments. There was modest reporting of measures to reduce risks of bias. The number of animals required to obtain 80% power with a significance level of 0.05 varied substantially across behavioural tests. In this comprehensive summary of the use of animal models of CIPN, we have identified areas in which the value of preclinical CIPN studies might be increased. Using both sexes of animals in the modelling of CIPN, ensuring that outcome measures align with those most relevant in the clinic, and the animal's pain contextualised ethology will likely improve external validity. Measures to reduce risk of bias should be employed to increase the internal validity of studies. Different outcome measures have different statistical power, and this can refine our approaches in the modelling of CIPN.

Association of HMOX-1 rs2071747 with sporadic Parkinson's disease in southern Han Chinese.

STUDY OBJECTIVES: To discover the associations between HMOX-1 and sporadic Parkinson's disease (PD). METHODS: Five hundred sporadic PD patients and 500 healthy controls were recruited in this study. Polymerase chain reaction (PCR) was used. RESULTS: The dominant model of HMOX-1 rs2071747 was shown statistically significant between PD patients and control after adjustment of age and gender (dominant model: p value: 0.045, OR: 1.51, 95% CI: 1.01-2.27, adjusted). The associations of additive model and dominant model of rs2071747 were also found (additive model: p value: 0.047; dominant model: p value: 0.035, OR: 1.55, 95% CI: 1.03, 2.34). CONCLUSIONS: We found the association of the dominant of HMOX1 rs2071747 with PD. We also found the associations of additive model and dominant model of HMOX1 rs2071747 with late onset PD (LOPD) patients. HIGHLIGHTS: • The dominant model of HMOX1 rs2071747 was associated with PD. • The additive model of HMOX1 rs2071747 was associated with LOPD. • The dominant model of HMOX1 rs2071747 was associated with LOPD.

A case report: anatomical translocation in tibial insertion of semitendinosus tendon after tibial lengthening.

BACKGROUND: There is the most common method for arthroscopic anterior cruciate ligament (ACL) reconstruction by using the semitendinosus and gracilis tendons and single-tunnel technique. However, anatomic translocation of hamstring tendon attachment is very rare. CASE PRESENTATION: A 45-year-old male who need to receive right knee ACL reconstruction due to sprain injury while playing table tennis was found to have a translocation at tibial attachment of semitendinosus tendon. The tibial insertion of left semitendinosus was then explored by ultrasound and found to be identical to the contralateral limb. The patient has a history of bilateral tibial lengthening. CONCLUSIONS: This is the first case as far as we know that reported anatomic translocation of the tibial attachment of the hamstring tendon after tibial lengthening. Surgeons should be aware of this specific situation when hamstring tendon need to be harvested to avoid unnecessary complications.

YY1 cooperates with TFEB to regulate autophagy and lysosomal biogenesis in melanoma.

Autophagy is a self-proteolytic process that degrades intracellular material to maintain cellular homeostasis. Transcription factor EB (TFEB) is the master activator that regulates the transcription of genes involved in autophagy and lysosomal biogenesis. However, the cotranscriptional factors of TFEB are rarely identified. Here, we found that Yin Yang 1 (YY1) regulated autophagy and lysosome biogenesis in melanoma cells. YY1 cooperates with TFEB to regulate autophagy through controlling the transcription of autophagy and lysosome biogenesis related genes. Moreover, suppression of YY1 enhanced the antitumor efficiency of vemurafenib both in vitro and in vivo. Collectively, these studies identify YY1 as a novel cotranscription factor of TFEB in regulating autophagy and lysosomal functions and suggest YY1 could be a therapeutic target in cancer treatment.

HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System.

The primate lentiviral accessory protein Nef downregulates CD4 and major histocompatibility complex class I (MHC-I) from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison to CD4 and MHC-I. We confirm that Nef excludes Ser5 from human immunodeficiency virus type 1 (HIV-1) virions by downregulating its cell surface expression via similar functional motifs required for CD4 downregulation. We find that Nef decreases both Ser5 and CD4 expression at steady-state levels, which are rescued by NH4Cl or bafilomycin A1 treatment. Nef binding to Ser5 was detected in living cells using a bimolecular fluorescence complementation assay, where Nef membrane association is required for interaction. In addition, Nef triggers rapid Ser5 internalization via receptor-mediated endocytosis and relocalizes Ser5 to Rab5+ early, Rab7+ late, and Rab11+ recycling endosomes. Manipulation of AP-2, Rab5, Rab7, and Rab11 expression levels affects the Nef-dependent Ser5 and CD4 downregulation. Moreover, although Nef does not promote Ser5 polyubiquitination, Ser5 downregulation relies on the ubiquitination pathway, and both K48- and K63-specific ubiquitin linkages are required for the downregulation. Finally, Nef promotes Ser5 colocalization with LAMP1, which is enhanced by bafilomycin A1 treatment, suggesting that Ser5 is targeted to lysosomes for destruction. We conclude that Nef uses a similar mechanism to downregulate Ser5 and CD4, which sorts Ser5 into a point-of-no-return degradative pathway to counteract its restriction.IMPORTANCE Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) express an accessory protein called Nef to promote viral pathogenesis. Nef drives immune escape in vivo through downregulation of CD4 and MHC-I from the host cell surface. Recently, Nef was reported to counteract a novel host restriction factor, Ser5, to increase viral infectivity. Nef downregulates cell surface Ser5, thus preventing its incorporation into virus particles, resulting in disruption of its antiviral activity. Here, we report mechanistic studies of Nef-mediated Ser5 downregulation in comparison to CD4 and MHC-I. We demonstrate that Nef binds directly to Ser5 in living cells and that Nef-Ser5 interaction requires Nef association with the plasma membrane. Subsequently, Nef internalizes Ser5 from the plasma membrane via receptor-mediated endocytosis, and targets ubiquitinated Ser5 to endosomes and lysosomes for destruction. Collectively, these results provide new insights into our ongoing understanding of the Nef-Ser5 arms race in HIV-1 infection.

The effect of perceived social support during early pregnancy on depressive symptoms at 6 weeks postpartum: a prospective study.

BACKGROUND: Postpartum depression was associated with maternal suffering and diminished functioning, increased risk of marital conflict as well as adverse child outcomes. Perceived social support during pregnancy was associated with postpartum depression among women. However, its causal relationship remains unclear. Therefore, we prospectively evaluate the association between perceived social support during early pregnancy and postpartum depressive symptoms. METHODS: We prospectively examined whether perceived social support during early pregnancy affected depressive symptoms at 6 weeks postpartum in a cohort of 3310 women. Perceived social support and postpartum depression were assessed by ENRICHD Social Support Instrument (ESSI) and the postpartum Edinburgh Postpartum Depression Scale (EPDS), respectively. Prevalence of postpartum depressive symptoms was 11.4% (EPDS cutoff≥10). As a test of heterogeneity of association in subpopulations, logistic regression models were performed to analyze the association between social support and postpartum depressive symptoms in strata which were defined by the potential confounder candidates. After multiple imputation, multivariable logistic regression was performed to assess the effect of social support on postpartum symptoms in individual items and total score. Two models were built. Model I adjusted for the variables associated with social support or postpartum depression and changed the association estimates by ≥10%. Model II adjusted for all variables that may be related to social support or postpartum depression. RESULTS: Significant associations between low perceived social support and postpartum depressive symptoms was found(Model I odds ratio: 1.63, 95% confidence interval: 1.15, 2.30; Model II odds ratio: 1.77, 95% confidence interval: 1.24-2.52). Stratified analyses showed that there was little evidence of heterogeneity of association in subpopulations by basic characteristics of participants. CONCLUSIONS: These findings suggest that early intervention may be able to help protect against depression symptoms at 6 weeks postpartum.

Intravasation Affects the Diagnostic Image Quality of Transvaginal 4-Dimensional Hysterosalpingo-Contrast Sonography With SonoVue.

OBJECTIVES: We aim to retrospectively analyze the diagnostic image quality of transvaginal 4-dimensional hysterosalpingo-contrast sonography from infertile patients and determine the significant influencing factors. METHODS: A total of 445 patients visiting infertility clinics were included in the study, of which 167 were primary infertile and 278 were secondary infertile. The factors were recorded, including age; examination time; infertility type; history of pelvic inflammatory disease, pelvic surgery, intrauterine surgery, and ectopic pregnancy; endometrial thickness; uterine position; ovarian position; 2-dimensional image quality; intravasation quantity, position, and time; balloon volume; and the dosage of contrast agent or the sterile saline solution. All the factors were compared among different diagnostic image quality groups. The method of rank logistic regression analysis was adopted to analyze the risk factors affecting the diagnostic image quality. RESULTS: Among the 445 infertile patients, 124 (27.9%) patients had intravasation occur during transvaginal 4-dimensional hysterosalpingo-contrast sonography. The diagnostic image quality between the 2 sonographers was consistent (Cronbach's alpha, 0.993). Different intravasation quantities, positions, and times; increased of balloon volume; and history of pelvic surgery were substantial risk factors for the diagnostic image quality. The diagnostic image quality diminished with the increase of intravasation. In the patient with cornual intravasation, the diagnostic image quality was substantially worse than that with non-cornual intravasation. Moreover, early onset of intravasation seriously affected the diagnostic image quality. CONCLUSIONS: In conclusion, intravasation affected the diagnostic image quality, especially early cornual massive intravasation.

LncRNA TUG1 promotes cisplatin resistance in esophageal squamous cell carcinoma cells by regulating Nrf2.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy with poor prognosis. The drug resistance compromises the efficacy of chemotherapy for ESCC. Long non-coding RNA taurine upregulated gene 1 (TUG1) has been identified as a promoter of cancer progression and chemotherapy resistance in many malignancies. However, the exact role of TUG1 in ESCC chemotherapy resistance remains unclear. In this study, we showed that TUG1 expression in TE-1-derived cisplatin (DDP)-resistant (TE-1/DDP) cells was higher than that in TE-1 cells. Furthermore, TUG1 promoted DDP resistance in TE-1 and TE-1/DDP cells by promoting cell proliferation, suppressing cell apoptosis, and elevating protein expression of the classical multi-drug resistance-related P-gp. In contrast, TUG1 knockdown exerted an opposite effect. Mechanistically, RNA pull-down and RNA immunoprecipitation assays confirmed that TUG1 directly bound to nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein and elevated Nrf2 protein expression. Moreover, Nrf2-neutralizing antibody effectively reversed the TUG1 overexpression-mediated promotion of ESCC cell resistance to DDP. In conclusion, our findings demonstrated that TUG1 promoted ESCC cell resistance to DDP, at least in part, through upregulating Nrf2.

[An investigation of vaccination in children with human immunodeficiency virus infection].

OBJECTIVE: To investigate the status of vaccination in children with human immunodeficiency virus (HIV) infection. METHODS: A questionnaire survey was performed in 148 children in Hunan province, China who were registered in China's Acquired Immune Deficiency Syndrome Comprehensive Response Information Management System up to December 31, 2016 and were aged <15 years at the time of confirmed diagnosis of HIV infection. The information on vaccination, diagnosis of HIV infection, and diagnosis and treatment of related diseases was collected. RESULTS: Of the 148 children with HIV infection, there were 70 boys (47.3%) and 78 girls (52.7%); 140 children had an age of 3.8 (0.2-14.8) years at the time of confirmed diagnosis, and 8 children refused to answer this question. Mother-to-child transmission was found in 133 children (91.7%), blood transmission in 1 child (0.7%), and unknown in 14 children (9.5%). Of the 148 children, 129 (87.2%) received antiviral therapy and 19 (12.8%) did not receive such treatment. The vaccination rates of hepatitis B vaccine, bacille Calmette-Guérin vaccine, poliomyelitis live attenuated vaccine and diphtheria-pertussis-tetanus vaccine ranged from 70.9% to 77.7%, which was significantly lower than the national level (≥97%); the vaccination rates of the other vaccines in the National Immunization Program gradually decreased with age. No severe adverse effects were reported after vaccination. CONCLUSIONS: Mother-to-child transmission is the main route of HIV infection in Chinese children. The diagnosis of children with HIV infection is significantly delayed, with low vaccination rates. Efforts should be made to strengthen early diagnosis, early treatment and vaccination in children with HIV infection, in order to improve their quality of life.

Probing the structural, electronic and magnetic properties of AgnSc (n = 1-16) clusters.

The structural, electronic and magnetic properties of AgnSc (n = 1-16) clusters have been studied on the basis of density functional theory and the CALYPSO structure prediction method. The optimized geometry exhibits that the growth process of Sc-doped silver clusters have a periodic structural change. The Ag atom grows around a basically invariant cluster core in each growth cycle. The Sc atom has a tendency to occupy the most highly coordinated position in the ground state. The infrared spectra, Raman spectra and photoelectron spectra of AgnSc clusters are forecasted and can be used to identify the structures of these clusters from experiments. The global maxima of the dissociation energy, the averaged binding energy and the gap of the energy level occur at n = 15 for the most stable AgnSc clusters, implying that the Ag15Sc can be perceived as a superatom. The magnetism analysis indicates that the magnetic moment of the Sc atom in AgnSc clusters decreases with the increase of the cluster. The change of the magnetic moment is proportional to the charge transfer between the Sc and Ag atoms.

A Subset of CD8αß+ Invariant NKT Cells in a Humanized Mouse Model.

Invariant NKT (iNKT) cells are unconventional innate-like T cells demonstrating potent antitumor function in conventional mouse models. However, the iNKT cell ligands have had limited efficacy in human antitumor clinical trials, mostly due to the profound differences in the properties and compositions of iNKT cells between the two species, including the presence of a CD8(+) subset of iNKT cells only in humans. To build reliable in vivo models for studying human iNKT cells, we recently developed the first humanized mouse model (hCD1d-KI) with human CD1d knocked in. To further humanize the mouse model, we now introduced the human invariant NKT TCRα-chain (Vα24Jα18) into the hCD1d-knockin mice. Similar to humans, this humanized mouse model developed a subset of CD8αß(+) iNKT cells among other human-like iNKT subsets. The presence of the CD8αß(+) iNKT cells in the thymus suggests that these cells developed in the thymus. In the periphery, these NKT cells showed a strong Th1-biased cytokine response and potent cytotoxicity for syngeneic tumor cells upon activation, as do human CD8αß(+) iNKT cells. The low binding avidity of iNKT TCRs to the human CD1d/lipid complex and high prevalence of Vß7 TCRß among the CD8(+) iNKT cells strongly point to a low avidity-based developmental program for these iNKT cells, which included the suppression of Th-POK and upregulation of eomesodermin transcriptional factors. Our establishment of this extensively humanized mouse model phenotypically and functionally reflecting the human CD1d/iNKT TCR system will greatly facilitate the future design and optimization of iNKT cell-based immunotherapies.

Herpes Simplex Virus 1 US3 Phosphorylates Cellular KIF3A To Downregulate CD1d Expression.

UNLABELLED: Herpes simplex virus 1 (HSV-1) causes one of the most prevalent herpesviral infections in humans and is the leading etiological agent of viral encephalitis and eye infections. Our understanding of how HSV-1 interacts with the host at the cellular and organismal levels is still limited. We and others previously reported that, upon infection, HSV-1 rapidly and efficiently downregulates CD1d cell surface expression and suppresses the function of NKT cells, a group of innate T cells with critical immunoregulatory function. The viral protein kinase US3 plays a major role in this immune evasion mechanism, and its kinase activity is required for this function. In this study, we investigated the cellular substrate(s) phosphorylated by US3 and how it mediates US3 suppression of CD1d recycling. We identified the type II kinesin motor protein KIF3A as a critical kinesin factor in the cell surface expression of CD1d. Interestingly, KIF3A is phosphorylated by US3 both in vitro and in infected cells. Mass spectrometry analysis of purified KIF3A showed that it is phosphorylated predominantly at serine 687 by US3. Ablation of this phosphorylation abolished US3-mediated downregulation of CD1d expression, suggesting that phosphorylation of KIF3A is the primary mechanism of HSV-1 suppression of CD1d expression by US3 protein. Understanding of the precise mechanism of viral modulation of CD1d expression will help to develop more efficient vaccines in the future to boost host NKT cell-mediated immune responses against herpesviruses. IMPORTANCE: Herpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We previously reported that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule CD1d to evade the antiviral function of NKT cells. Here we identified the key cellular motor protein KIF3A as a cellular substrate phosphorylated by US3, and this phosphorylation event mediates US3-induced immune evasion.

[Pararectus approach for treatment of acetabular both-column fracture combined with translocation of quadrilateral surface].

OBJECTIVE: To study the clinical effect and surgical operating points of pararectus approach for the internal fixation of acetabular both-column fractures with concurrent displaced quadrilateral plate fractures. METHODS: From January 2012 to December 2013, in the Third Affiliated Hospital of Southern Medical University, 15 patients with acetabular both-column fractures and displaced quadrilateral plate fractures were surgically managed through the pararectus approach. There were 11 male and 4 female patients, with an average age of 40 years (from 19 to 61 years). According to Judet-Letournel classification, there were 9 anterior column plus posterior hemitransverse fractures, 6 both-column fractures, 8 cases involving the pelvic fracture. All these fractures were treated through the pararectus approach, in the horizontal position with general anesthesia. The pre-bended plate was placed in interior pelvic ring to fix the anterior wall, anterior column and quadrilateral plate in direct sight. Then, the posterior column was exposed and fixed with antegrade lag screw. Patients were followed up in 4 weeks, 12 weeks, 6 months, 1 year after the operation, and the anteroposterior radiograph of pelvis and the X-ray examination of the fractured hip was performed. RESULTS: All the 15 cases underwent the operation successfully. Postoperative X-ray and CT exams showed excellent and good reduction of anterior column, posterior column and quadrilateral plate, with none surgical complication occurred. According to the Matta radiological evaluation postoperatively, reduction of acetabular fracture was rated as excellent in 9 cases, good in 3 cases and poor in 3 cases. The rate of excellent and good was 12/15. After 8 to 18 months' follow-up (median follow-up time was 14 months), all the patients gained bone union. According to the modified Merle D'Aubigne and Postel scoring system, 9 cases were excellent, 4 were good, and 2 were fair. The rate of excellent and good was 13/15. CONCLUSIONS: Surgical management of acetabular fractures through the pararectus approach can provide adequate exposure of reducing and fixing both-column acetabular fractures with concurrent displaced quadrilateral plate fractures, which has a good effect in clinical application.

Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11): a national observational cohort study.

BACKGROUND: On the basis of the results of the randomised clinical trial HPTN 052 and observational studies, WHO has recommended that antiretroviral therapy be offered to all HIV-infected individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. Whether or not such a public health approach is feasible and the outcomes are sustainable at a large scale and in a developing country setting has not previously been assessed. METHODS: In this retrospective observational cohort study, we included treated and treatment-naive HIV-positive individuals with HIV-negative partners of the opposite sex who had been added to the national HIV epidemiology and treatment databases between Jan 1, 2003 and Dec 31, 2011. We analysed the annual rate of HIV infection in HIV-negative partners during follow-up, stratified by treatment status of the index partner. Cox proportional hazards analyses were done to examine factors related to HIV transmission. FINDINGS: Based on data from 38,862 serodiscordant couples, with 101,295·1 person-years of follow-up for the seronegative partners, rates of HIV infection were 2·6 per 100 person-years (95% CI 2·4-2·8) among the 14,805 couples in the treatment-naive cohort (median baseline CD4 count for HIV-positive partners 441 cells per µl [IQR 314-590]) and 1·3 per 100 person-years (1·2-1·3) among the 24,057 couples in the treated cohort (median baseline CD4 count for HIV-positive partners 168 cells per µl [62-269]). We calculated a 26% relative reduction in HIV transmission (adjusted hazard ratio 0·74, 95% CI 0·65-0·84) in the treated cohort. The reduction in transmission was seen across almost all demographic subgroups and was significant in the first year (0·64, 0·54-0·76), and among couples in which the HIV-positive partner had been infected by blood or plasma transfusion (0·76, 0·59-0·99) or heterosexual intercourse (0·69, 0·56-0·84), but not among couples in which the HIV-positive partner was infected by injecting drugs (0·98, 0·71-1·36). INTERPRETATION: Antiretroviral therapy for HIV-positive individuals in serodiscordant couples reduced HIV transmission across China, which suggests that the treatment-as-prevention approach is a feasible public health prevention strategy on a national scale in a developing country context. The durability and generalisability of such protection, however, needs to be further studied. FUNDING: Chinese Government's 12th Five-Year Plan, the National Natural Science Foundation of China, and the Canadian International Development Research Centre.

Characterization of a PIAS4 homologue from zebrafish: insights into its conserved negative regulatory mechanism in the TRIF, MAVS, and IFN signaling pathways during vertebrate evolution.

Members of the protein inhibitor of activated STAT (PIAS) family are key regulators of various human and mammalian signaling pathways, but data on their occurrence and functions in ancient vertebrates are limited. This study characterizes for the first time to our knowledge a PIAS4 homologue (PIAS4a) from zebrafish. Structurally, this zebrafish PIAS4a (zfPIAS4a) shares a number of conserved functional domains with mammalian PIAS4 proteins, including the scaffold attachment factor A/B/acinus/PIAS box, PINIT, and RING-finger-like zinc-binding domains and a highly acidic domain in the C-terminal region. Subcellular localization analysis shows that zfPIAS4a is a nuclear-localized protein and that the C terminus of the molecule harbors strict nuclear localization signals. Functionally, zfPIAS4a expression can be dramatically induced by the stimulation of polyinosinic-polycytidylic acid and zebrafish IFN1. It acts as a critical negative regulator of the TIR domain-containing adapter inducing IFN-ß, mitochondrial antiviral signaling (MAVS), and IFN signaling pathways, and it is the first PIAS protein that plays a role in the MAVS-mediated pathway to be identified. The structure and functionality of PIAS4 seem highly conserved from zebrafish to mammals, making zebrafish an attractive model for screens designed to uncover genes involved in IFN- and inflammatory cytokine-induced signaling pathways. This study provides preliminary evidence that the PIAS regulatory mechanism already existed in fish during vertebrate evolution. It presents valuable clues for improving the understanding of not only the negative regulation of cytokine signaling in fish but also the evolutionary history of the PIAS family from fish to mammals as a whole.

Sound Touch Elastography for Noninvasive Assessment of Liver Stiffness in Patients With Chronic Heart Failure.

Heart failure (HF) can damage various organs, including the liver, a phenomenon known as "cardiohepatic syndrome." The latter is characterized by liver congestion and hepatic artery hypoperfusion, which can lead to liver damage. In this study, we aimed to assess liver damage quantitatively in chronic HF (CHF) with sound touch elastography (STE). A total of 150 subjects were enrolled, including HF with reduced ejection fraction (HFrEF) groups (left ventricular ejection fraction ≤40%, n = 45), HF with mildly reduced ejection fraction (HFmrEF) groups (left ventricular ejection fraction between 41% and 49%, n = 40), and right-sided HF (RHF) groups (n = 25); normal groups (n = 40). Liver stiffness measurement (LSM) was performed in all subjects by STE. The other hepatic parameters were also measured. The LSM was 5.4 ± 1.1 kPa in normal subjects and increased slightly to 5.9 ± 0.7 kPa in patients with HFmrEF. However, the HFrEF and RHF groups had significantly higher LSMs of 8.4 ± 2.0 kPa and 10.3 ± 2.7 kPa, respectively. The LSM of HFrEF was significantly higher than that of HFmrEF, whereas the increase in LSM in patients with RHF was significant relative to HFmrEF and HFrEF. In addition, the other parameters showed abnormal values in only RHF and HFrEF. In conclusion, STE is a useful clinical technique for the noninvasive evaluation of liver stiffness associated with CHF, which could help patients with CHF manage their treatment regimens.

Tantalum Particles Promote M2 Macrophage Polarization and Regulate Local Bone Metabolism via Macrophage-Derived Exosomes Influencing the Fates of BMSCs.

In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.

Semiactive robotic-arm system versus patient-specific instrumentation in primary total knee arthroplasty: Efficacy and accuracy.

OBJECTIVE: To compare the difference in efficacy and accuracy during total knee arthroplasty (TKA) among robotic-arm system, patient-specific instrumentation (PSI) and conventional TKA (COTKA). METHODS: Retrospective analysis of 90 advanced knee osteoarthritis (OA) patients in our hospital between June 2019 and December 2020 was conducted. Patients were divided into robotic arm-assisted (RA)TKA (group A), PSITKA (group B) and COTKA (group C), 30 cases in each group. The operation time, intraoperative bleeding, and length of hospital stay were counted. Imaging data of hip-knee-ankle angle (HKA), posterior condylar angle (PCA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and sagittal tibial component angle (sTCA) were statistically analyzed. The postoperative recovery of the patients was evaluated by Knee Society Score (KSS) and the Western Ontario Mac Master University Index Score (WOMAC). RESULTS: Group A had the least intraoperative bleeding. For operation time, group A was the longest compared with group B and group C (P < 0.05), while group B was longer than group C (P < 0.05). There was no significant difference in HKA, LDFA, and MPTA among the three groups, and the lower limb alignments were all restored to the neutral position. PCA of group A and B were both smaller than that of group C and closer to 0° (P < 0.05), but the difference between group A and B was not statistically significant. The sTCA in group A was significantly better than group B, and group B was significantly better than group C (P < 0.05). There were no significant differences in function scores among the three groups. CONCLUSION: Compared to the PSI and CO, RA is more minimally invasive and more accurate in radiographic results.

Simulation-Based Learning Combined with Case and Problem-Based Learning in the Clinical Education of Joint Surgery.

OBJECTIVE: Traditional education of clinical training mainly relies on a single mode of lecture-based learning (LBL), in which the teacher lectures and the students listen, and the teaching effect is often unsatisfactory. This study aims to explore the effect of simulation-based learning (SBL) combined with case and problem-based learning (CPBL) teaching mode in the clinical education of joint surgery. DESIGN: Through objective evaluation of joint surgery students' theoretical knowledge and clinical skills, and subjective evaluation of teaching quality by anonymous questionnaire, the teaching effects of LBL teaching mode, CPBL teaching mode and SBL combined with CPBL teaching mode in clinical teaching of joint surgery were compared. SETTING AND PARTICIPANTS: Sixty students who participated in the standardized training of residents in the Center for Joint Surgery, Southwest Hospital, Army University, China from March 2020 to September 2021 were selected and randomly divided into groups A, B, and C, with 20 students in each group. Group A adopted traditional LBL mode, group B adopted CPBL mode, and group C adopted SBL combined with CPBL mode. RESULTS: The scores of theoretical knowledge, clinical skills and total score of group C were (86.40 ± 9.76), (92.15 ± 4.49), (88.70 ± 5.75) points respectively, which were significantly higher than (78.80 ± 10.50), (86.60 ± 8.79), (81.92 ± 6.97) points in group B, and (80.50 ± 6.64), (85.35 ± 7.99), (82.44 ± 5.97) points in group A, the difference was statistically significant (p < 0.05). The scores of 5 self-evaluation items, i.e., learning interest, self-learning ability, problem-solving ability, clinical skills and comprehensive competency were (18.90 ± 1.22), (18.85 ± 1.01), (18.75 ± 1.13), (18.90 ± 1.22), (18.50 ± 1.02), (18.80 ± 0.81) points in group C, which were higher than (15.90 ± 1.41), (14.30 ± 2.47), (13.95 ± 2.01), (14.50 ± 1.63), (14.70 ± 1.38) points in group B, and (11.65 ± 2.90), (10.05 ± 1.69), (9.75 ± 1.67), (14.35 ± 1.90), (12.75 ± 2.12) points in group A, the difference was statistically significant (p <0.05). The satisfaction of students in group C (95.00%) was significantly better than that in group B (80.00%) and group A (65.00%), and the difference was statistically significant (p < 0.05). CONCLUSION: SBL combined with CPBL teaching mode can effectively improve the theoretical knowledge and clinical skills of the students, which could improve self-assessment and teaching satisfaction rate, and is worthy of application and promotion in the clinical teaching of joint surgery.