Overexpression of LAG3, TIM3, and A2aR in adenoid cystic carcinoma and mucoepidermoid carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines. MATERIALS AND METHODS: Custom made human salivary gland tissue microarrays included 81 AdCCs, 52 MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6 kinase (p-S6) and ERK1/2 (p-ERK1/2 ), and TGF-ß1 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in vitro studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection. RESULTS: The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF-ß1, slightly related to p-ERK1/2 and p-S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC-LM cell line was significantly reduced. CONCLUSIONS: These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC-LM cell and correlated with TGF-ß1 and oncogenic signaling pathways.

Expression of HHLA2, TMIGD2, and GITR in salivary gland adenoid cystic carcinoma and mucoepidermoid carcinoma.

BACKGROUND: Mucoepidermoid carcinoma and adenoid cystic carcinoma are the two most common malignancies of salivary gland. Our study aims to explore the role of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced tumor necrosis factor receptor in adenoid cystic carcinoma and mucoepidermoid carcinoma, and the relationship between human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, glucocorticoid-induced TNF receptor, oncogenic signaling molecules, and cluster of differentiation 8. METHODS: Custom-made human salivary gland tissue microarrays included 81 Adenoid cystic carcinoma, 52 mucoepidermoid carcinoma, 76 normal salivary gland, and 14 pleomorphic adenoma samples. Immunohistochemical analysis of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor, oncogenic phosphorylated Erk1/2 , the epithelial-mesenchymal transition (EMT) molecule transforming growth factor ß1, and cluster of differentiation 8 was performed with salivary gland tissue microarray of human samples. RESULTS: According to a digital pathological system, we analyzed the correlation of immunostaining. The expression levels of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were significantly enhanced in the adenoid cystic carcinoma and mucoepidermoid carcinoma, compared with those of pleomorphic adenoma and NSG samples. However, the expression levels of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were independent of the pathological grade of malignancy of mucoepidermoid carcinoma and histological pattern of adenoid cystic carcinoma. They were closely related to phosphorylated Erk1/2 and transforming growth factor ß1, but negligibly related to cluster of differentiation 8. CONCLUSIONS: These results described that certain immune checkpoint molecules, namely, human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were overexpressed in Adenoid cystic carcinoma and mucoepidermoid carcinoma, but were independent of pathological grade, and may relate to transforming growth factor ß1, phosphorylated Erk1/2, and cluster of differentiation 8.

Association between periodontal disease, tooth loss and liver diseases risk.

AIM: The purpose of this study is to assess the associations between periodontal disease, tooth loss and liver diseases. MATERIALS AND METHODS: PubMed and Embase databases were utilized to search eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used as effect size to assess the associations between periodontal disease, tooth loss and liver diseases risk. RESULTS: Our results indicated positive associations between periodontal disease and non-alcoholic fatty liver disease (NAFLD) (OR = 1.19, 95% CI = 1.06-1.33), liver cirrhosis (OR = 2.28, 95% CI = 1.50-3.48) and elevated transaminase level risk (OR = 1.08, 95% CI = 1.02-1.15). Moreover, tooth loss could increase NAFLD (OR = 1.33, 95% CI = 1.12- 1.56) and liver cancer risk (OR = 1.34, 95% CI = 1.04-1.74), and every five increment in tooth loss was associated with 5% increased liver cancer risk (OR = 1.05, 95% CI = 1.01 - 1.10) with a linear relationship. In addition, tooth loss had a positive tendency towards liver cirrhosis risk (OR = 2.03, 95% CI = 0.85-4.85) although there was no statistical significance. CONCLUSION: Periodontal disease and tooth loss are positively associated with liver diseases including NAFLD, elevated transaminase level, liver cirrhosis and liver cancer.

Overexpression of Malic Enzyme 2 Indicates Pathological and Clinical Significance in Oral Squamous Cell Carcinoma.

Our study investigated the expression of malic enzyme 2 (ME2) in human oral squamous cell carcinoma (OSCC) and associated pathological and clinical pattern. We demonstrated that human OSCC tissues expressed a high level of ME2, and the overexpression of ME2 is closely connected to a high pathological grade, lymphatic metastasis, large tumor size and human papillomavirus (HPV) (P < 0.001). Similarly, high levels of ME2 expression in OSCC tissue were shown to be correlated with poor prognosis (P < 0.05). The expression of ME2 was correlated with Slug, SOX2, and aldehyde dehydrogenase-1 (ALDH1) immunoreactivity.ME2 was shown to be overexpressed in OSCC tissue and indicated a poor prognosis for OSCC. ME2 may be correlated with several immune markers.

Expression of inositol polyphosphate 4-phosphatase type II and the prognosis of oral squamous cell carcinoma.

Inositol polyphosphate 4-phosphatase type II (INPP4B) is a phosphoinositide phosphatase that plays complex roles in the pathogenesis of different tumors. We aimed to explore the expression, clinicopathological significance, and prognostic value of INPP4B in oral squamous cell carcinoma (OSCC). Tissue microarrays that included samples from 176 primary OSCCs, 42 normal mucosae, and 69 dysplastic tissues were used for immunostaining analyses of INPP4B protein. Aperio ScanScope CS scanner and aperio quantification software were used to scan the microarrays and score the staining, respectively. We also evaluated the correlation between INPP4B expression and clinical parameters, pathological grades, node-positive status, and immune-related markers. Expression of INPP4B was statistically significantly upregulated in human primary OSCC tissues compared with dysplastic and normal tissues. Additionally, we found that patients with strong expression of INPP4B had a statistically significantly poorer overall survival than patients with weak expression of INPP4B. Furthermore, our study indicated that expression of INPP4B in OSCC was positively associated with expression of p-S6Ser235/236 , p-CADSer1859 , and certain immune checkpoints (B7-H4, Galectin-9). Therefore, INPP4B may be an independent prognostic indicator for patients with OSCC, in which it might function as an oncoprotein.

Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the most frequent malignancies in the salivary glands. The purpose of this study was to explore the roles of sine oculis homeobox homolog 1 (SIX1), malic enzyme 2 (ME2), and AP-2 complex subunit mu (AP2M1) in AdCC and MEC, as well as the potential relationship between SIX1, ME2, AP2M1, and proliferation marker cyclin D1. MATERIAL AND METHODS: Immunohistochemistry was performed on human salivary gland tissue microarrays that contained 76 normal salivary glands (NSGs), 14 pleomorphic adenomas (PMAs), 81 AdCCs, and 52 MECs. RESULTS: We observed that the expression levels of SIX1 and ME2 were significantly elevated in AdCC and MEC when compared with NSG and PMA. In addition, we detected that AP2M1 was overexpressed in AdCC and MEC when compared with NSG. We also found that SIX1 and AP2M1 were positively associated with cyclin D1. CONCLUSIONS: These results may prove that SIX1 and AP2M1 are involved in the proliferation of AdCC and MEC to cause tumor growth.

Human Cytomegalovirus Immediate Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus.

The mechanisms underlying neurodevelopmental damage caused by virus infections remain poorly defined. Congenital human cytomegalovirus (HCMV) infection is the leading cause of fetal brain development disorders. Previous work has linked HCMV infection to perturbations of neural cell fate, including premature differentiation of neural progenitor cells (NPCs). Here, we show that HCMV infection of NPCs results in loss of the SOX2 protein, a key pluripotency-associated transcription factor. SOX2 depletion maps to the HCMV major immediate early (IE) transcription unit and is individually mediated by the IE1 and IE2 proteins. IE1 causes SOX2 downregulation by promoting the nuclear accumulation and inhibiting the phosphorylation of STAT3, a transcriptional activator of SOX2 expression. Deranged signaling resulting in depletion of a critical stem cell protein is an unanticipated mechanism by which the viral major IE proteins may contribute to brain development disorders caused by congenital HCMV infection.IMPORTANCE Human cytomegalovirus (HCMV) infections are a leading cause of brain damage, hearing loss, and other neurological disabilities in children. We report that the HCMV proteins known as IE1 and IE2 target expression of human SOX2, a central pluripotency-associated transcription factor that governs neural progenitor cell (NPC) fate and is required for normal brain development. Both during HCMV infection and when expressed alone, IE1 causes the loss of SOX2 from NPCs. IE1 mediates SOX2 depletion by targeting STAT3, a critical upstream regulator of SOX2 expression. Our findings reveal an unanticipated mechanism by which a common virus may cause damage to the developing nervous system and suggest novel targets for medical intervention.

Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase.

Congenital human cytomegalovirus (HCMV) infection is the leading cause of neurological disabilities in children worldwide, but the mechanisms underlying these disorders are far from well-defined. HCMV infection has been shown to dysregulate the Notch signaling pathway in human neural progenitor cells (NPCs). As an important downstream effector of Notch signaling, the transcriptional regulator Hairy and Enhancer of Split 1 (Hes1) is essential for governing NPC fate and fetal brain development. In the present study, we report that HCMV infection downregulates Hes1 protein levels in infected NPCs. The HCMV 72-kDa immediate-early 1 protein (IE1) is involved in Hes1 degradation by assembling a ubiquitination complex and promoting Hes1 ubiquitination as a potential E3 ubiquitin ligase, followed by proteasomal degradation of Hes1. Sp100A, an important component of PML nuclear bodies, is identified to be another target of IE1-mediated ubiquitination. A C-terminal acidic region in IE1, spanning amino acids 451 to 475, is required for IE1/Hes1 physical interaction and IE1-mediated Hes1 ubiquitination, but is dispensable for IE1/Sp100A interaction and ubiquitination. Our study suggests a novel mechanism linking downregulation of Hes1 protein to neurodevelopmental disorders caused by HCMV infection. Our findings also complement the current knowledge of herpesviruses by identifying IE1 as the first potential HCMV-encoded E3 ubiquitin ligase.

Increased Expression of LAMTOR5 Predicts Poor Prognosis and Is Associated with Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma.

Late endosomal/lysosomal adaptor and MAPK and mTOR activator 5 (LAMTOR5) is a novel oncoprotein associated with several human malignancies, but its clinical role in head and neck squamous cell carcinoma (HNSCC) remains unclear. The present study aims to investigate the clinical and pathological significance of LAMTOR5 in HNSCC. We utilized immunohistochemical staining of human tissue microarrays (210 primary HNSCC, 42 normal oral mucosae, 69 oral epithelial dysplasia, and 68 metastasis lymph nodes) to explore the clinical and pathological significance of LAMTOR5 in HNSCC. Additionally, expression level of LAMTOR5 in immunoreactivity of Pten conditional knock out (Pten cKO) mice HNSCC was also assessed. We found LAMTOR5 was overexpressed in human and Pten cKO mice HNSCC, and its expression was significantly associated with patients' overall survival, lymph node metastasis and lymph node grade. Furthermore, LAMTOR5 expression was significantly correlated with the expression of p-AktSer473, p-S6Ser235/236, immune checkpoints (PD-L1, Galectin 9, VISTA and B7-H4) and macrophage markers (CD68 and CD163). In Pten cKO mice HNSCC, it was also significantly correlated with VISTA and F4/80. Consequently, we consider that high expression of LAMTOR5 might be a poor prognostic indicator and correlated with the immunosuppression of tumor microenvironment.

Clinical evidence of prevention strategies for capecitabine-induced hand-foot syndrome.

Hand-foot syndrome (HFS) is the most common adverse effect of capecitabine-containing chemotherapy. The purpose of this study was to assess the efficacies of various prevention and treatment strategies for capecitabine-induced HFS. Searches of the PubMed and Embase databases were performed to identify relevant studies. The risk ratio (RR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate the efficacies of these prevention and treatment strategies. Publication bias was evaluated using Begg's and Egger's tests. Overall and subgroup analyses were conducted. All statistical analyses were conducted with Stata software version 12.0. Seventeen eligible studies were included. Our results indicated that celecoxib was significantly associated with a lower incidence of grade ≥2 capecitabine-induced HFS without heterogeneity (RR = 0.43, 95% CI = 0.23-0.81, I2  = 0.0%). However, pyridoxine and topical urea/lactic acid were not effective toward preventing capecitabine-induced grade 1, 2, 3, ≥1 or ≥2 HFS. Moreover, pyridoxine was not effective in treating capecitabine-induced HFS. Similar results were obtained by subgroup analysis. Our results indicate that celecoxib has potential prophylactic efficacy for capecitabine-induced HFS. However, pyridoxine and topical urea/lactic acid are not associated with a decrease in the incidence of capecitabine-induced HFS.

MicroRNA miR-21 attenuates human cytomegalovirus replication in neural cells by targeting Cdc25a.

UNLABELLED: Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily manifesting as neurological disorders. HCMV infection alters expression of cellular microRNAs (miRs) and induces cell cycle arrest, which in turn modifies the cellular environment to favor virus replication. Previous observations found that HCMV infection reduces miR-21 expression in neural progenitor/stem cells (NPCs). Here, we show that infection of NPCs and U-251MG cells represses miR-21 while increasing the levels of Cdc25a, a cell cycle regulator and known target of miR-21. These opposing responses to infection prompted an investigation of the relationship between miR-21, Cdc25a, and viral replication. Overexpression of miR-21 in NPCs and U-251MG cells inhibited viral gene expression, genome replication, and production of infectious progeny, while shRNA-knockdown of miR-21 in U-251MG cells increased viral gene expression. In contrast, overexpression of Cdc25a in U-251MG cells increased viral gene expression and production of infectious progeny and overcame the inhibitory effects of miR-21 overexpression. Three viral gene products-IE1, pp71, and UL26-were shown to inhibit miR-21 expression at the transcriptional level. These results suggest that Cdc25a promotes HCMV replication and elevation of Cdc25a levels after HCMV infection are due in part to HCMV-mediated repression of miR-21. Thus, miR-21 is an intrinsic antiviral factor that is modulated by HCMV infection. This suggests a role for miR-21 downregulation in the neuropathogenesis of HCMV infection of the developing CNS. IMPORTANCE: Human cytomegalovirus (HCMV) is a ubiquitous pathogen and has very high prevalence among population, especially in China, and congenital HCMV infection is a major cause for birth defects. Elucidating virus-host interactions that govern HCMV replication in neuronal cells is critical to understanding the neuropathogenesis of birth defects resulting from congenital infection. In this study, we confirm that HCMV infection downregulates miR-21 but upregulates Cdc25a. Further determined the negative effects of cellular miRNA miR-21 on HCMV replication in neural progenitor/stem cells and U-251MG glioblastoma/astrocytoma cells. More importantly, our results provide the first evidence that miR-21 negatively regulates HCMV replication by targeting Cdc25a, a vital cell cycle regulator. We further found that viral gene products of IE1, pp71, and UL26 play roles in inhibiting miR-21 expression, which in turn causes increases in Cdc25a and benefits HCMV replication. Thus, miR-21 appears to be an intrinsic antiviral factor that represents a potential target for therapeutic intervention.

The outcome of the proximal radial artery arteriovenous fistula.

BACKGROUND: Guidelines recommend placing native arteriovenous fistulas (AVFs) as far distally in the upper extremity as possible. If there are adequate veins and adequate arteries, a wrist fistula, which offers notably lower risks than grafts and catheters, would be the first choice for long-term hemodialysis. With increasing failure and difficulty to create wrist fistulas, we reviewed outcomes of the proximal radial AVF (PRAAVF) and demonstrate that it is an effective technique. METHODS: A systemic literature research was conducted in PubMed and related bibliographies. The focus of data extraction was primary failure, primary patency rates, and secondary patency rates after 1 and 2 years. Estimates were pooled with the random effects model, and meta-regression and sensitivity analysis were performed to explore heterogeneity. RESULTS: According to selection criteria formulated a priori, 10 articles (n = 1310) were included and finally analyzed after screening 1687 articles. The pooled primary failure was 12.3% (95% confidence interval [CI], 7.6%-17.0%; χ(2) = 70.8, I(2) = 87.3%), the primary patency, including primary failure, was 73.6% (95% CI, 52.4%-94.9%; χ(2) = 71.3, I(2) = 97.2%) at 1 year and 70.5% (95% CI, 50.6%-90.5%; χ(2) = 58.8, I(2) = 96.6%) at 2 years. Secondary patency was 80.0% (95% CI, 72.8%-87.2%; χ(2) = 24.42, I(2) = 75.4%) at 1 year and 73.7% (95% CI, 65.2%-82.2%; χ(2) = 28.51, I(2) = 79.0%) at 2 years. Individual variate meta-regression analysis found the definition of primary failure was a significant source of heterogeneity (P = .009). Steal syndromes developed in four of 832 (0.5%) of the PRAAVFs, and venous hypertension developed in four of 284 (1.4%). CONCLUSIONS: The PRAAVF presented low to moderate primary failure and high primary and secondary patency rates with acceptable complications. Consideration of the specific fistula is required when creating a vascular access, especially when a wrist fistula has failed or is predicted to be unsuccessful.

Later passages of neural progenitor cells from neonatal brain are more permissive for human cytomegalovirus infection.

Congenital human cytomegalovirus (HCMV) infection is the most frequent infectious cause of birth defects, primarily neurological disorders. Neural progenitor/stem cells (NPCs) are the major cell type in the subventricular zone and are susceptible to HCMV infection. In culture, the differentiation status of NPCs may change with passage, which in turn may alter susceptibility to virus infection. Previously, only early-passage (i.e., prior to passage 9) NPCs were studied and shown to be permissive to HCMV infection. In this study, NPC cultures derived at different gestational ages were evaluated after short (passages 3 to 6) and extended (passages 11 to 20) in vitro passages for biological and virological parameters (i.e., cell morphology, expression of NPC markers and HCMV receptors, viral entry efficiency, viral gene expression, virus-induced cytopathic effect, and release of infectious progeny). These parameters were not significantly influenced by the gestational age of the source tissues. However, extended-passage cultures showed evidence of initiation of differentiation, increased viral entry, and more efficient production of infectious progeny. These results confirm that NPCs are fully permissive for HCMV infection and that extended-passage NPCs initiate differentiation and are more permissive for HCMV infection. Later-passage NPCs being differentiated and more permissive for HCMV infection suggest that HCMV infection in fetal brain may cause more neural cell loss and give rise to severe neurological disabilities with advancing brain development.

Natural antisense transcripts of UL123 packaged in human cytomegalovirus virions.

In this study, we demonstrated that antisense transcripts of human cytomegalovirus (HCMV) UL123, UL21.5 and cellular GAPDH genes were present in highly purified virions. These virion RNAs were delivered into the host cells upon infection, and de novo synthesized ones appeared in the infected cell at the immediate early stage. Although the sequence of UL123 antisense transcripts in virions is uncertain, we found that these transcripts in Towne-infected human fibroblasts had novel transcriptional start sites (TSSs) with various 5'-terminal deletions of open reading frame (ORF) 59. These findings not only provide new insight into the composition of HCMV virions but also reveal a possible viral strategy for initiating latent infection and switching between latent and productive infections.

[Double-pulley combined with suture bridge technique for fixation of comminuted fractures of distal patella pole].

OBJECTIVE: To investigate the clinical effect of double pulley combined with suture bridge in the treatment of comminuted fracture of the lower pole of the patella. METHODS: From January 2018 to June 2020, 15 patients with comminuted fracture of the lower pole of the patella were treated with double pulley and suture bridge technology, including 9 males and 6 females, aged 28 to 68 years old with an average of (42.4±9.6) years old. All patients had obvious knee joint pain and limited movement after injury. All knee joints were examined by X-ray and CT, which confirmed that they were all comminuted fractures at the lower level of the patella. After operation, X-ray films of the knee joint were taken regularly to understand the fracture healing, the Insall Salvati index was measure, the range of motion of the joint was recorded, and the function of the knee joint was evaluateed by the Bostman scoring system. RESULTS: All the 15 patients were followed up for 7 to 24 months with an average of (11.4±4.2) months, and there was no obvious anterior knee pain. At the last follow-up, the knee joint range of motion of the affected limb was 105° to 140° with an average of (128.5±12.8) °, and the Insall Salvati index was 0.79 to 1.12 with an average of (0.92±0.18). The X-ray film showed that the patella was bone healing, and no anchor fell off, broken, or displaced fracture block was found. Bostman patellar fracture function score was 27.85±2.06, 13 cases were excellent, 2 cases were good. CONCLUSION: Double pulley technique combined with suture bridge technique is reliable for reduction and fixation of comminuted fracture of the lower pole of patella, and patients can start functional exercise early after operation.

Sequential damage assessment of the posterolateral complex of the knee joint: a finite element study.

BACKGROUND: The posterolateral complex (PLC), which consists of the popliteus tendon (PT), lateral collateral ligament (LCL), and popliteofibular ligament (PFL), is an indispensable structure of the knee joint. The aim of this study was to explore the functionality of the PLC by determining the specific role of each component in maintaining posterolateral knee stability. METHODS: A finite element (FE) model was generated based on previous material property data and magnetic resonance imaging of a volunteer's knee joint. The injury order of the PLC was set as LCL, PFL, and PT. A combined compressive load of 1150 N and an anterior tibial load of 134 N was applied to the tibia to investigate tibial displacement (TD). Tibial external rotation (TER) and tibial varus angulation (TVA) were measured under bending motions of 5 and 10 Nm. The instantaneous axis of rotation (IAR) of the knee joint under different rotation motions was also recorded. RESULTS: The TD of the intact knee under a combined compressive load of 1150 N and an anterior tibial load of 134 N matched the values determined in previous studies. Our model showed consistent increases in TD, TVA, and TER after sequential damage of the PLC. In addition, sequential disruption caused the IAR to shift superiorly and laterally during varus rotation and medially and anteriorly during external rotation. In the dynamic damage of the PLC, LCL injury had the largest effect on TD, TVA, TER, and IAR. CONCLUSIONS: Sequential injury of the PLC caused considerable loss of stability of the knee joint according to an FE model. The most significant structure of the PLC was the LCL.

[Coronal curvature of tibial leads to malalignment of tibial prosthesis after total knee arthroplasty].

OBJECTIVE: To investigate the effect of tibial coronal curvature on the alignment of tibial prosthesis in patients undergoing total knee arthroplasty (TKA). METHODS: From July 2019 to April 2021, 100 patients with knee osteoarthritis were treated with total knee arthroplasty. Before operation, the full-length films of lower limbs were taken and the tibial bowing angle(TBA) was measured. TBA more than 2° was tibial bending, which was divided into tibial bending group and non bending group. There were 40 cases in tibial bending group, 9 males and 31 females, aged 56 to 84 years old with an average of (69.22±7.10) years. There were 60 cases in the non bending group, 19 males and 41 females, aged from 51 to 87 years old with an average of (70.80±7.21) years. The preoperative tibial length (TL) and medial proximal tibial angle (MPTA) were measured and compared between the two groups. The full-length X-rays of the lower limbs were taken again 3 days to 1 week after operation. The medial angle of the tibial component coronal aligement angle (TCCA) and the outilier rate of force line of the tibial prosthesis were measured and compared between the two groups. Pearson method was used to analyze the correlation between TCCA and age, TCCA and height, TCCA and weight, TCCA and BMI, TCCA and TBA, TCCA and TL, TCCA and MPTA; Spearman method was used to analyze the correlation between TCCA and gender, TCCA and Kellgren-Lawrence(K-L) grade. RESULTS: All 100 patients successfully completed the operation and obtained satisfactory full-length X-rays in standing position. There was no significant difference in TL, MPTA and TCCA between bending group and non bending group(P>0.05). The outilier rate of force line in tibial bending group was 22.5%, and that in non bending group was 6.67%, the difference was statistically significant(P<0.05). The correlation study found that TCCA was strongly correlated with TBA(r=-0.702, P<0.01), weakly correlated with MPTA(r=0.311, P<0.01), and had no correlation with other parameters(P>0.05). CONCLUSION: In patients with knee osteoarthritis undergoing total knee arthroplasty, tibial bending will lead to poor force line of tibial prosthesis. During operation, attention should be paid to osteotomy of proximal tibial vertical tibial mechanical axis and correct installation of prosthesis to avoid poor alignment of prosthesis.

Biomaterial-mediated modulation of oral microbiota synergizes with PD-1 blockade in mice with oral squamous cell carcinoma.

Because a host's immune system is affected by host-microbiota interactions, means of modulating the microbiota could be leveraged to augment the effectiveness of cancer therapies. Here we report that patients with oral squamous cell carcinoma (OSCC) whose tumours contained higher levels of bacteria of the genus Peptostreptococcus had higher probability of long-term survival. We then show that in mice with murine OSCC tumours injected with oral microbiota from patients with OSCCs, antitumour responses were enhanced by the subcutaneous delivery of an adhesive hydrogel incorporating silver nanoparticles (which inhibited the growth of bacteria competing with Peptostreptococcus) alongside the intratumoural delivery of the bacterium P. anaerobius (which upregulated the levels of Peptostreptococcus). We also show that in mice with subcutaneous or orthotopic murine OSCC tumours, combination therapy with the two components (nanoparticle-incorporating hydrogel and exogenous P. anaerobius) synergized with checkpoint inhibition with programmed death-1. Our findings suggest that biomaterials can be designed to modulate human microbiota to augment antitumour immune responses.

Total hip revision with custom-made spacer and prosthesis: A case report.

BACKGROUND: Both periprosthetic joint infections (PJIs) and severe femoral segmental defects are catastrophic complications of total hip arthroplasty (THA), and both present a significant challenge in revisional surgery. There are limited data available to guide clinical decision making when both occur concurrently. CASE SUMMARY: A 61-year-old woman presented with a 6-mo history of a sinus tract at the site of her original THA incision. Radiological imaging revealed a total hip joint implant with an ipsilateral segmental femoral defect. Based on histological, radiological, laboratory, and clinical features, a diagnosis of concurrent chronic PJI and segmental femoral defect (Type IIIB, Paprosky classification) was made. After multidisciplinary team discussion, three-dimensional (3D)-printed, custom-made antibiotic spacers were created that could be used to mold antibiotic-loaded cement spacer. These were placed following PJI debridement in the first stage of revision surgery. After the PJI was eliminated, a 3D-printed, custom-made, femoral prosthesis was created to repair the considerable femoral defect. After 20-mo follow-up, the patient had excellent functional outcomes with a near-normal range of hip movement. So far, neither evidence of recurrent infection nor loosening of the prosthesis has been observed. CONCLUSION: We describe a case of "two-stage, custom-made" total hip revision to treat PJI with a concurrent segmental femoral defect. Use of a personalized, 3D-printed spacer and proximal femoral prosthesis led to satisfactory hip function and no early postoperative complications. Use of a customized implant provides surgeons with an alternative option for patients where no suitable spacer or implant is available. However, the long-term function, longevity, and cost-effectiveness of the use of custom-made prostheses have yet to be fully explored.