Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma.

BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.

Relationships between intravoxel incoherent motion parameters and expressions of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) in patients with cervical cancer.

AIM: To determine the associations of intravoxel incoherent motion (IVIM) parameters with expression of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), and evaluate the performance of the combined model established based on IVIM and clinicopathological parameters in predicting PD-L1and PD-1 status of cervical cancer (CC) patients. MATERIALS AND METHODS: Seventy-eight consecutive CC patients were enrolled prospectively and underwent magnetic resonance imaging (MRI) including IVIM. IVIM quantitative parameters were measured, compared, and correlated with PD-L1 and PD-1 expression. Independent factors related to PD-L1 and PD-1 positivity were identified and were used to establish the combined model. The combined model's diagnostic performance was evaluated using the receiver operating characteristic (ROC) analysis. The Shapley additive explanation (SHAP) algorithm was used to explain the contribution of each parameter in the combined model. RESULTS: The real diffusion coefficient (D) value was significantly lower in the PD-L1-positive group than in the PD-L1-negative group (0.64 ± 0.12 versus 0.72 ± 0.11, p=0.021). The PD-1-positive and PD-1-negative groups showed similar trends (0.63 ± 0.13 versus 0.73 ± 0.09, p=0.003). Parametrial invasion, lymph node status, pathological grade, FIGO (International Federation of Gynecology and Obstetrics) staging, and D values were independently associated with PD-L1 and PD-1expression. A combined model incorporating these parameters showed good discrimination with the sensitivity, specificity of 90.9%, 82.6% for PD-L1, and 93.5%, 72% for PD-1. According to the SHAP value, FIGO staging and pathological grade were the most influential features of the prediction model. CONCLUSION: IVIM parameters were found to correlate with PD-L1 and PD-1 expression. The combined model, incorporating parametrial invasion, lymph node status, pathological grade, FIGO staging, and D values, showed good discrimination in predicting PD-L1 and PD-1 status, providing the basis for CC immunotherapy.

Effect and mechanism of recombinant human fibroblast growth factor 18 on osteoporosis in OVX mice.

OBJECTIVES: This study aimed to investigate the effect and the mechanism of recombinant human fibroblast growth factor 18 (rhFGF18) on postmenopausal osteoporosis. METHODS: The effect of rhFGF18 on the proliferation and apoptosis of osteoblasts and the mechanism underlying such an effect was evaluated using an oxidative stress model of the MC3T3-E1 cell line. Furthermore, ovariectomy was performed on ICR mice to imitate estrogen-deficiency postmenopausal osteoporosis. Bone metabolism and bone morphological parameters in the ovariectomized (OVX) mice were evaluated. RESULTS: The results obtained from the cell model showed that FGF18 promoted MC3T3-E1 cell proliferation by activating the extracellular signal-regulated kinase (ERK) and p38 instead of c-Jun N-terminal kinase (JNK). FGF18 also prevented cells from damage inflicted by oxidative stress via inhibition of apoptosis. After FGF18 administration, the expression level of anti-apoptotic protein Bcl-2 in the mice was upregulated, whereas those of the pro-apoptotic proteins Bax and caspase-3 were downregulated. Administering FGF18 also improved bone metabolism and bone morphological parameters in OVX mice. CONCLUSIONS: FGF18 could effectively prevent bone loss in OVX mice by enhancing osteoblastogenesis and protecting osteoblasts from oxidative stress-induced apoptosis.

Comparative Transcriptomic Analysis of the Flavor Production Mechanism in Yogurt by Traditional Starter Strains.

Synergistic fermentation of milk by Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus is one of the key factors that determines the quality of yogurt. In this study, the mechanism whereby yogurt flavor compounds are produced by mixture of S. thermophilus SIT-20.S and L. delbrueckii ssp. bulgaricus SIT-17.B were investigated by examining these strains' flavor production, growth, and gene transcription. The results showed that yogurt produced by a 10:1 mixture of the aforementioned strains had the highest abundance of acetoin, whereas yogurt produced by a 1:1 mixture had the highest abundance of diacetyl and acetaldehyde. In addition, the growth of S. thermophilus SIT-20.S was enhanced in the 10:1 mixture. Transcriptomic analysis revealed differentially expressed genes in the flavor-compound-related pathways of S. thermophilus SIT-20.S and L. delbrueckii ssp. bulgaricus SIT-17.B in yogurts produced by 10:1 and 1:1 mixture compared with those produced by either strain alone. Mixed fermentations regulated the expression of genes related to glycolysis, resulting in an increase of pyruvate, which is an important precursor for diacetyl and acetoin synthesis. The gene encoding the acetoin reductase (SIT-20S_orf01454) was decreased in S. thermophilus SIT-20.S, which ensured the accumulation of acetoin. Besides, gene encoding the acetaldehyde dehydrogenase (SIT-20S_orf00949) was upregulated in S. thermophilus SIT-20.S, and the expression of alcohol dehydrogenase (SIT-20S_orf01479; SIT-17B_orf00943) was downregulated in both strains, maintaining the abundance of acetaldehyde. In addition, the gene encoding the NADH oxidase (SIT-17B_orf00860) in L. delbrueckii ssp. bulgaricus SIT-17.B were upregulated, which promoted the accumulation of diacetyl and acetoin. In conclusion, we characterized the mechanism by which S. thermophilus and L. delbrueckii ssp. bulgaricus synergistically generated yogurt flavor compounds during their production of yogurt and highlighted the importance of appropriate proportions of fermentation starters for improving the flavor of yogurts.

[Immunotherapy advances for lung cancer combined with chronic obstructive pulmonary disease].

Lung cancer is a major public health problem worldwide, with high rates of morbidity and mortality. It often coexists with chronic obstructive pulmonary disease (COPD), the diagnosis and management of which often receives insufficient attention. In particular, the presence of COPD has significant implications for the clinical management of lung cancer patients. This review systematically assesses the influence of COPD on the efficacy of immunotherapy and the occurrence of immune-related adverse events in patients with lung cancer, identifies existing challenges and proposes avenues for future research in this field.

Causal associations between serum amino acid levels and osteoarthritis: a Mendelian randomization study.

OBJECTIVE: The association between serum amino acid (AA) levels and osteoarthritis (OA) risk remains unclear. METHOD: We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effects of serum AA levels on the OA risk by using summary-level genome-wide association study (GWAS) data. Inverse variance weighted (IVW) and Wald ratio were used as the main analysis. We also applied MR-Egger, Weighted median and Robust Adjusted Profile Score (MR.RAPS) methods. Heterogeneity and horizontally pleiotropic outliers were checked. The causal effects of AAs on early-onset all OA were explored. We also performed multivariable MR (MVMR) and conducted the bidirectional MR. RESULTS: The results suggested that genetically predicted alanine (Ala), tyrosine (Tyr) and isoleucine (Ile) levels were significantly associated with OA risk [e.g., association between Ala and hip/knee OA risk: OR = 0.82, 95% confidence interval (CI) = 0.75-0.90, P = 1.54E-05]. The study yielded little evidence of associations between genetically predicted AA levels with early-onset all OA risk. When adjusting the body mass index (BMI) in the MVMR model, suggestive causal effects of Ala and Tyr were also identified, while the effects of Ile substantially attenuated with OA risk. No significant associations between OA and AA levels were observed after testing for bidirectionality. CONCLUSIONS: Some AAs, such as Ala, Tyr and Ile likely affects the OA risk especially at hip or knee joints. The findings highlight the important role that serum AAs might play in the development of OA and provided new treatment approaches to OA.

[Cumulative sum control chart analysis of soft tissue balance in total knee replacement assisted by electronic pressure sensor].

OBJECTIVE: To explore the training ability of pad to guide the balance of soft tissue by drawing cumulative sum (CUSUM) control chart total knee arthroplasty (TKA) sensor. METHODS: The data of 73 knees of TKA assisted by electronic gasket initially completed by a senior physician were analyzed retrospectively. There were 8 males (8 knees) and 52 females (65 knees), with an average age of (67.5±5.9) years (57-82 years). The balance of the internal and external space of knee joint was measured at 0°, 45°, 90°, and 120°, in order to observe the pressure distribution of the medial and la-teral compartments, and CUSUM learning curve was drawn. RESULTS: In 0° extension, the medial pressure was higher than the lateral (P < 0.01), when flexion began, the medial and lateral pressures decreased, and became stable and approximately equal during 45°-120°. In the learning curve, by knee 34, CUSUM 0° curve crossed the acceptable control line from above, which showed that it was easy to grasp the soft tissue balance at 0° position through sensor learning. CUSUM 45° curve was above the unacceptable control line in the end, which meant that it was difficult to grasp the technique at the mid-flexion angle. CUSUM 90° and 120° crossed the acceptable control line from above by knee 68 and 57 respectively, which showed that the technique of balance could be improved with the aid of more cases. CONCLUSION: The electronic pressure sensor can effectively guide the soft tissue balance in TKA. The learning process is simple and does not increase the risk of complications. It can be used as a tool for learning TKA soft tissue balance technology to guide joint surgeons to further master or improve the soft tissue balance technology.

[Progress in pre-chronic obstructive pulmonary disease].

Pre-chronic obstructive pulmonary disease (Pre-COPD) refers to individuals with chronic respiratory symptoms, structural abnormalities, and/or functional abnormalities, in the absence of airflow limitation, who may develop persistent airflow limitation over time. COPD is characterized by high prevalence and great heterogeneity and complexity. Early multidimensional identification and promotion of early prevention, management and treatment of Pre-COPD can help delay or halt the development of COPD, which has significant public health implications. This review aimed to summarize the definition, relevant cohorts, clinical trials, and other research progress in pre-COPD in order to improve the understanding of individuals with pre-COPD and improve early prevention and management of COPD.

[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial.

BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM. PATIENTS AND METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%). CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.

Difference responses of soil fungal communities to cattle and chicken manure composting application.

AIMS: Cattle and poultry manure composting are often applied on agricultural lands but the fungal community composition before and after application in soils is still unclear. This study describes soil fungal diversity after manure applications contribute to the correct resource use of livestock and poultry manures. METHODS AND RESULTS: Fresh manure samples were obtained from 10 beef cow farms and 12 egg-laying poultry farms at five distinct phases of rearing. Surface soil samples were collected from vegetable plots within the farms after manure application at 15, 30 and 45 t hm-2 . Using high-throughput sequencing techniques, the ITS region was used to describe soil fungus populations. The fungal OTUs, Chao1 and ACE of cattle manure were relatively higher in the fattening stage (>12 months), the OTUs and ACE of chicken manure were the highest in the initial laying stage (16-24 weeks). The fungal diversity indices of vegetable soils had no linear change after cow or chicken manure application compared with the control. Ascomycota (84.7% of total sequences), Neocallimastigomycota (9.69%) and Basidiomycota (4.6%) were the dominant phyla in cattle manure. Ascomycota (88.9%) also predominated in chicken manure followed by Basidiomycota (8.9%). Following both cattle and chicken manure applications, the abundance of Ascomycota decreased, whereas Basidiomycota and Chytridiomycota increased in the soils. None of the dominant genus increased or decreased linearly with the increase of cattle and chicken composting application rate. The fungal-dominant genera of the soils with and without manure composting application were mostly affected by soil pH and EC than manure. Pearson's correlation analysis revealed that organic matter, Cu and Hg contents were strongly linked to the fungal diversity and the abundance of specific taxa in cattle manure. In chicken manure, OM, TN and Zn were major factors controlling the fungal diversity and community composition. Soil pH, EC and Cu, Zn, Cd, Hg and As content had pronounced effects on the beneficial and pathogenic genus in soil with and without manure composting. Beneficial fungal genus such as Aspergillus, Plectosphaerella, Acremonium, Meyerozyma and fungal pathogenic such as Fusarium, Cladosporium, Verticillium were sensitive to properties (EC, pH, OM) and heavy metals (Cu, Zn, Hg) contents of the environment relatively. This study can serve as an applicable contribution helping in farms management (especially to cattle and poultry breeding) and improving their resource use of livestock and poultry manures. CONCLUSIONS: Soil heterogeneity rather than manure determines fungal communities in the vegetable fields, but we can encourage the sensible use of cattle and chicken manures in agroecosystems. SIGNIFICANCE AND IMPACT OF THE STUDY: This study will help farmers regulate the dosage of feed components which can increase the number of beneficial fungal genus or reduce the number of pathogenic fungal genus, improve their resource use of livestock and poultry manures and encourage the sensible use of cattle and chicken manures in agroecosystems.

DNA methylation and waist-to-hip ratio: an epigenome-wide association study in Chinese monozygotic twins.

PURPOSE: Epigenetic signatures such as DNA methylation may be associated with specific obesity traits. We performed an epigenome-wide association study (EWAS) by combining with the waist-to-hip ratio (WHR)-discordant monozygotic (MZ) twin design in an attempt to identify genetically independent DNA methylation marks associated with abdominal obesity in Northern Han Chinese and to determine the causation underlying. METHODS: A total of 60 WHR discordant MZ twin pairs were selected from the Qingdao Twin Registry, China. Generalized estimated equation (GEE) model was used to regress the methylation level of CpG sites on WHR. The Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was used to assess the temporal relationship between methylation and WHR. Gene expression analysis was conducted to validate the results of differentially methylated analyses. RESULTS: EWAS identified 92 CpG sites with the level of P < 10 - 4 which were annotated to 32 genes, especially CADPS2, TUSC5, ZCCHC14, CORO7, COL23A1, CACNA1C, CYP26B1, and BCAT1. ICE FALCON showed significant causality between DNA methylation of several genes and WHR (P < 0.05). In region-based analysis, 14 differentially methylated regions (DMRs) located at 15 genes (slk-corrected P < 0.05) were detected. The gene expression analysis identified the significant correlation between expression levels of 5 differentially methylated genes and WHR (P < 0.05). CONCLUSIONS: Our study identifies the associations between specific epigenetic variations and WHR in Northern Han Chinese. These DNA methylation signatures may have value as diagnostic biomarkers and provide novel insights into the molecular mechanisms of pathogenesis.

[Application of trifoliate flap design of radial forearm flap in reconstruction of defects after mouth floor cancer resection].

Objective: To evaluate the effect of trifoliate flap design of radial forearm flap in reconstruction of defects after mouth floor cancer resection. Methods: From June 2016 to December 2019, 12 patients with defect after resection of mouth floor cancer were treated with trifoliate flap design of radial forearm flap. All of these patients were T2 stage, included 9 well-differentiated squamous cell carcinoma (SCC) and 3 moderate differentiated SCC. The defect size ranged from 8.0 cm×6.0 cm to 5.0 cm×4.5 cm after resection of tumor and neck dissection. All defects were repaired with trifoliate flap design of radial forearm flap. The flap size ranged from 8.0 cm×2.0 cm to 4.0 cm×1.5 cm, the donor site was sutured directly on Z plasty. Results: All flaps completely survived well. Both the wound and the donor site were stage Ⅰ healing. With the average follow-up of 38.6 months, the swallowing and speech function were satisfactory. Conclusions: Trifoliate flap design of radial forearm flap can effectively repair the postoperative defect of mouth floor cancer, and the donor site can be directly sutured on Z plasty. This technique can avoid forearm scar caused by skin grafting and the formation of the second donor site.

[Efficacy and safety of venetoclax combined with azacitidine versus CAG regimen combined with decitabine in elderly patients with relapsed acute myeloid leukemia].

Objective: To compare the efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) versus CAG regimen combined with decitabine (DAC) in elderly patients with relapsed acute myeloid leukemia (AML). Methods: From January 2018 to August 2020, the clinical data of forty-five elderly patients with relapse AML at the First Affiliated Hospital of Soochow University were retrospectively analyzed, including 31 males and 14 females. The median age was 66 (60-80) years old. Eighteen patients were administrated with VEN and AZA, while the other 27 were in CAG with DAC. The complete remission (CR) rate, partial remission (PR) rate, total remission rate (ORR), adverse events and overall survival (OS) were compared between the two groups. Results: At the end of the treatment, the ORR in VEN with AZA group was 77.8% (14/18); including 11 CR and 3 PR. In CAG with DAC group, the ORR was 37.0% (10/27); including 8 CR and 2 PR (P=0.007). Subgroup analysis suggested that VEN with AZA had a higher ORR in patients stratified as intermediate and poor-risk (P=0.013) or with DNA methylation mutations (P=0.007). Main adverse events in both groups were bone marrow suppression, infections, nausea and vomiting, anorexia and fatigue. Grade Ⅲ-Ⅳ cytopenia developed in lower incidence of VEN with AZA group, such as leukopenia (66.7% vs. 100%, P=0.002), anemia (50.0% vs. 92.6%, P=0.002), thrombocytopenia (72.2% vs. 96.3%, P=0.031) and neutropenia (61.1% vs. 92.6%, P=0.014). In addition, less grade Ⅲ-Ⅳ infections occurred in VEN with AZA group (66.7% vs. 33.3%, P=0.028), as well as grade Ⅲ-Ⅳ gastrointestinal events (40.7% vs. 11.1%, P=0.032), grade Ⅲ-Ⅳ fatigue (55.6% vs.11.1%, P=0.003) compared with CAG with DAC group. The 1-year OS in VEN with AZA group versus CAG with DAC group was 42.9% and 31.6% respectively (P=0.150). Conclusion: VEN combined with AZA proves favorable efficacy and tolerablity in elderly patients with relapsed AML.

[Robotic assisted artificial hip and knee arthroplasty is an inevitable trend in the future].

Artificial joint arthroplasty, such as total hip and total knee arthroplasty, is one of the most successful procedures in orthopedics. The quality of life of these patients can be improved significantly through relieving pain, correcting the deformity and improving joint function. Although hip and knee arthroplasty currently are routine surgeries for patients with late stage joint diseases, post-operative complications like leg length discrepancy, dislocation or instability, limp and uncertain reason pain are still common. The position of the implants plays important roles in all these complications. Robotic assisted joint arthroplasty can not only provide 3D pre-operative visual planning, but also can assist to fulfill the pre-operation plan perfectly. But the current joint arthroplasty robots cannot carry out automatic personalized pre-operation planning, and also have the shortcomings of low efficiency and high cost etc. However, based on their current performance and with the help of artificial intelligence and better algorithm, we believe that joint arthroplasty will be more and more precisive, intelligent and minimally invasive, which is an inevitable trend in the development of joint surgery.

[Effect of the acetabular cup positioning and leg length restoration after total hip arthroplasty using robotic-assisted surgery system].

Objective: To assess the improvement of the robotic-assisted total hip arthroplasty (rTHA) regarding the acetabular cup positioning and the leg length restoration. Methods: Clinical data of 246 patients undergoing primary unilateral THA from September 2019 to June 2021 in Peking University Third Hospital were retrospectively reviewed, including patients treated with rTHA (n=113) and conventional THA (cTHA) (n=133). Thirty-seven male patients along with 76 females were enrolled into the rTHA group with a mean age of (62±9) years. In comparison, the average age of cTHA group was (60±12) years with 59 males and 74 females. The postoperative inclination and anteversion of the acetabular cup and the rate of acetabular cup within the Lewinnek and Callanan "safe zone" were documented and analyzed. For the patient with normal or surgically restored contralateral hip, the leg length discrepancy was also measured and compared between the two groups. Results: The overall mean postoperative inclination and anteversion was 39.0°±5.5° and 14.1°±5.1°, respectively. No statistically significant difference was found between the rTHA and cTHA group regarding postoperative inclination (39.3°±2.9° vs 38.7°±7.0°, P=0.383) and anteversion (13.4°±4.3° vs 14.7°±5.6°, P=0.054). In rTHA group, 97.3%(110/113) of the cups were implanted within the Lewinnek"safe zone"(75.9%(101/133) in cTHA group) and 94.7%(107/113) were within the Callanan"safe zone"(66.2%(88/133) in cTHA group), and those were both higher in rTHA group (both P<0.01). There was no significant difference in postoperative leg length discrepancy between the two groups (P=0.445). Meanwhile, 29(23.0%) cases of cTHA group had leg length discrepancy more than 5 mm, and it was 9.7%(9/93) in rTHA group. Conclusion: It indicated the benefit of rTHA in acetabular cup positioning as well as the leg length restoration.

[Comparison of alignment and position of prosthesis between portable accelerometer-based navigation device and conventional instrumentation in total knee arthroplasty with valgus deformity].

Objective: To explore the differences of alignment and position of prosthesis between portable accelerometer-based navigation device (PAD) and conventional instrumentation (CI) in total knee arthroplasty (TKA) with valgus deformity. Methods: Patients with knee osteoarthritis and valgus deformity who underwent primary TKA in Peking University Third Hospital from January 2017 to December 2020 were enrolled in this retrospective study and were divided into PAD group and CI group according to the surgical instruments. Five male patients and 44 female patients were included with a mean age of (67.2±7.0) years. The differences in preoperative general data, preoperative and postoperative alignment between the two groups were studied. Results: A total of 49 patients (25 patients in the PAD group and 24 in the CI group) were enrolled in this study. There were no statistically significant differences in gender, age, height, weight, body mass index, surgical side, preoperative hip-knee-ankle (HKA) angle, preoperative HKA angle deviation, Keblish classification and Ranawat classification between the two groups (all P>0.05). There was no significant difference in the accuracy of postoperative HKA angle (2.0°±1.4° vs 3.0°±2.2°, P=0.082), coronal femoral component angle (CFCA) (1.5°±1.2° vs 2.1°±1.6°, P=0.144) and coronal tibial component angle (CTCA) (1.2°±0.8° vs 1.3°±1.0°, P=0.695) between the two groups; but the standard deviation of the above-mentioned three indices in PAD group were all smaller than those in CI group. The rate of outliers of postoperative HKA angle of the PAD group was smaller than that in the CI group (P<0.05), but there was no significant difference in the rate of outliers of CFCA and CTCA between the two groups (both P>0.05). Conclusion: TKA assisted by PAD can provide good alignment and prosthesis position in patients with valgus deformity, and it is superior to TKA with CI in terms of precision and rate of outliers of postoperative overall alignment of lower extremity.

[Relationship between valve ablation and bladder function in children with posterior urethral valves disorder].

This study is to investigate the effect of valve ablation on bladder function in patients with posterior urethral valves. The clinical data of patients with posterior urethral valves who received urodynamic examination before and after valve ablation were retrospectively analyzed.The bladder compliance improved during urine storage after operation, and the maximum detrusor pressure decreased during micturition. The postoperative urinary system ultrasound showed that the residual urine volume of the group with significantly improved upper urinary tract hydrocephalus was significantly less than that of the group with no improvement. The bladder compliance was significantly higher than that of the group with no improvement, and the maximum urine flow rate was significantly higher than that of the group with no improvement (all P<0.05). Valve ablation has limited effect on improving bladder function in patients with PUV. Valve incision can help improve the maximum bladder volume, residual urine volume and maximum urinary flow rate. It has a certain effect on bladder compliance and maximum detrusor pressure.

[A multicenter cross-sectional study of quality of life and nonsurgical treatment in patients with knee osteoarthritis].

Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (ß=-0.521, P=0.036); patients aged ≥64 years had lower PCS than those aged<55 years (ß=-0.636, P=0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (ß=1.063, P<0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (ß=-0.860, P=0.002), while the PCS of those with severe clinical symptoms was much lower (ß=-1.126, P<0.001). Patients treated with combination therapy had higher PCS than untreated patients (ß=0.731, P=0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (ß=-0.712, P=0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (ß=-1.183, P=0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

[Labor progression characteristics of primiparous term singleton pregnant women complicated with adenomyosis].

Objective: To analyze the labor progression characteristics of primiparous term singleton pregnant women with adenomyosis. Methods: From April 2014 to May 2021, pregnant women underwent regular antenatal examination in Peking University Third Hospital were enrolled in this retrospective study, 109 primiparous term pregnant women with adenomyosis who underwent singleton, primipara, cephalic and vaginal delivery were referred as the adenomyosis group, while 109 pregnant women without adenomyosis primiparous term pregnant women at the same time were referred as the control group. The general clinical information, labor process intervention, pregnancy outcomes and labor course time of the two groups were analyzed. Results: (1) General clinical conditions: the pre-pregnancy uterine volume of the adenomyosis group was larger than that of the control group [(66.8±23.7) vs (41.4±13.1) cm3, P<0.05]. The proportion of assisted reproductive pregnancy and endometriosis in the adenomyosis group were higher than those in the control group [31.2% (34/109) vs 7.3% (8/109); 31.2% (34/109) vs 5.5% (6/109); all P<0.05]. There were no significant differences in maternal age, gestational age at delivery, pre-pregnancy body mass index, gestational weight gain, gravidity, incidence of pregnancy complications (gestational diabetes mellitus, pre-eclampsia and thyroid diseases) and premature rupture of membranes between the two groups (all P>0.05). (2) Labor process intervention and maternal and fetal outcomes: postpartum hemorrhage was higher in the adenomyosis group than the control group (median: 300 vs 260 ml, P=0.018). There were no significant differences in the proportion of labor onset, use of oxytocin, artificial rupture of membranes, perineal laceration Ⅲ and above, episiotomy, newborn weight and 1-minute Apgar score between the two groups (all P>0.05). (3) Time of labor process: there were no significant differences between the two groups in the time required for the first stage, third stage, total stage and cervical dilation 0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7 cm (all P>0.05). The time required for cervical dilation 7-8, 8-9, 9-10 cm and the second stage of labor in adenomyosis group (median: 20, 18, 15 and 12 minutes, respectively) were shorter than those of the control group (median: 23, 23, 23 and 26 minutes, respectively), and the differences were statistically significant (all P<0.05). (4) The effect of endometriosis on labor: there was no significant difference in the effect of endometriosis on labor in adenomyosis group (P>0.05). Conclusions: The labor process of primiparous term pregnant women with adenomyosis is significantly accelerated after the cervical dilatation for 7 cm, which should be closely observed. The third stage of labor course is managed aggressively with drugs to prevent postpartum hemorrhage.