[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

[Clinical study of lumbar stability after unilateral biportal endoscopy in the treatment of degenerative lumbar diseases].

Objectives: To investigate the clinical efficacy of unilateral biportal endoscopy (UBE) in the treatment of degenerative lumbar disease (DLD) and its impact on postoperative lumbar stability. Methods: This is a retrospective case series study. A total of 109 cases of DLD treated with UBE in the Department of Orthopaedic, Beijing Chaoyang Hospital Affiliated to Capital Medical University from July 2020 to June 2022 were analyzed retrospectively. There were 47 males and 62 females, aged (53.3±8.2) years (range: 21 to 80 years). The surgical segments were single segment in 80 cases, two segments in 25 cases, and three segments in 4 cases. The low back pain and leg pain of visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score and Oswestry disability index (ODI) were evaluated before and after operation. The modified MacNab criteria were used for evaluation of the clinical consequences. Postoperative three-dimensional lumbar CT was performed to observe the preservation of the facet joints and the angle of the medial surface of the facetectomy(ß angle). At 12 months after surgery, X ray of the flexion and extension lumbar spine were reviewed. The comparison and analysis of the data were conducted using paired sample t tests or generalized estimation equations. Results: All 109 patients underwent operative procedures successfully. The operation time was (94.5±37.1) minutes (range:56 to 245 minutes), the times of X ray was 6.8±4.0 (range:4 to 16 times), and the days of hospitalization was (5.3±3.7) days (range:4 to 14 days). Complications included dural tears in 4 cases, transient lower limb numbness in 4 cases, epidural hematoma in 2 case. The follow-up time was (19.6±7.2) months (range:12 to 36 months). The postoperative low back pain VAS, leg pain VAS, JOA score and ODI were significantly improved(all P<0.05). According to the modified MacNab criteria, the excellent and good rate was 88.99%(97/109) at 12 months after surgery. One case underwent revision surgery because of recurrent lumbar disc herniation. In term of radiographic evaluation, the area of the surgical side facet joints after UBE surgery was reserved more than 60%. The ß angle was less than 90° in all patients. After 12 months of surgery, there was no surgical segment instability or spondylolisthesis by the X-ray of the flexion and extension lumbar spine. Conclusion: UBE can achieve satisfactory clinical efficacy in the treatment of DLD, and maintain the stability of the lumbar spine.

[A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey].

Objective: To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors. Methods: From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions. Results: Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects (χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients (χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications (χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment (R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not (OR=1.83, P<0.001). Conclusions: Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Surgical treatment of nasopharyngeal cancer - a consensus recommendation from two Chinese associations.

BACKGROUND: Surgical treatment is playing an increasingly important role in the management of nasopharyngeal carcinoma (NPC). This consensus focuses on the indications for optimal surgery, and surgical methods in the whole process of treatment for NPC to provide a useful reference to assist these difficult clinical decisions. METHODOLOGY: A thorough review of available literature on NPC and surgery was conducted by the Association for the prevention and treatment of nasopharyngeal carcinoma in China, international exchange and promotion Association for medicine and healthcare, and the Committee on nasopharyngeal cancer of Guangdong provincial anticancer association. A set of questions and a preliminary draft guideline was circulated to a panel of 1096 experienced specialists on this disease for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the experts in two authoritative medical science and technology academic groups in the prevention and treatment of NPC in China for review and reconsideration. RESULTS: The initial round of questions showed variations in clinical practice even among similar specialists, reflecting the lack of high-quality supporting data and resulting difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of surgery, including indications and surgical approaches. CONCLUSION: By standardizing the surgical indications and practice, we hope not only to improve the surgical outcomes, but also to highlight the key directions of future clinical research in the surgical management of NPC.

[Basic principles, design elements, advantages and challenges of emulated target trial].

Cohort studies have unique advantages such as good representation of subjects, large sample size, and long follow-up time, but the difficulty in controlling confounders is the main obstacle to their insufficient causal inference. On the contrary, randomized controlled trial (RCT) research has absolute advantages in controlling confounding factors, but human, material, and ethical aspects limit its organizational implementation. With the accumulation of real-world cohort research data in recent years, emulated target trial (ETT) following the design principles of RCT research in large cohort studies has attracted more attention. ETT research based on cohort data produces more accurate research conclusions and provides new ideas for real-world cohort data analysis. This paper aims to introduce the basic principles, design elements, and advantages and challenges of ETT research to provide a reference for medical researchers to carry out ETT.

[Comparison of quality-of-life after proximal gastrectomy with double tract reconstruction versus gastric tube reconstruction in patients with proximal gastric cancer].

Objective: To compare the surgical safety and postoperative quality of life between proximal gastrectomy with double tract reconstruction (PG-DT) and proximal gastrectomy with gastric tube reconstruction (PG-GT) for proximal gastric cancer. Methods: This was a retrospective cohort study of clinical and follow-up data of 99 patients with proximal gastric cancer who had undergone double tract or gastric tube surgery in Nanjing Drum Tower Hospital from January 2016 to September 2021. We allocated them to two groups according to surgical procedure, namely a double tract group (PG-DT, 50 patients) and gastric tube group (PG-GT, 49 patients). Proximal gastrectomy with double tract reconstruction entails constructing a Roux-en-Y esophagojejunostomy after severing the proximal stomach, and then constructing a side-to-side anastomosis between the residual stomach and the jejunum to establish an anti-reflux barrier and thus minimize postoperative gastroesophageal reflux. Proximal gastrectomy with gastric tube reconstruction entails severing the proximal gastric stomach, constructing a tubular shaped gastric remnant, and then using a linear stapler to directly anastomose the posterior wall of the esophagus to the anterior wall of the resultant gastric tube. The primary end point was the quality of life of the two groups 1 year postoperatively (post-gastrectomy syndrome assessment scale: the higher the scores for change in body mass, food intake per meal, meal quality subscale, total physical health measurement, and total mental health measurement, the better the quality-of-life, and the higher the scores for other indicators, the worse the quality-of-life). The secondary end points were intraoperative and postoperative status, changes in nutritional status 1, 3, 6, and 12 months postoperatively, and long-term postoperative complications (gastroesophageal reflux, anastomotic stenosis, intestinal obstruction, and gastric emptying disorder 1 year postoperatively). Results: In the PG-DT group, there were 35 (70%) men and 15 (30%) women, 33 (66.0%) patients were aged <65 years, and 37 (74.0%) of them had a body mass index of 18-25 kg/m2; whereas in the PG-GT group, there were 41 (83.7%) men and eight (16.3%) women, 21 (42.9%) patients aged <65 years, and 34 (69.4%) patients with a body mass index of 18-25 kg/m2. There were no significant differences in baseline data between the two groups except for age (P=0.021). There were no significant differences in intraoperative blood loss, number of lymph node dissected, length of hospital stay, and incidence of perioperative complications between the two groups (all P>0.05). Compared with the PG-GT group, the incidence and severity of postoperative reflux esophagitis were significantly lower in the PG-DT group (4.0% [2/50] vs. 26.5% [13/49], χ2=13.507, P=0.009). The incidences of postoperative anastomotic stenosis, intestinal obstruction, and gastric retention did not differ significantly between the two groups (all P>0.05). Patients in the PG-DT group had better quality-of-life scores for esophageal reflux (2.8 [2.3,4.0] vs. 4.8 [3.8,5.0], Z=3.489, P<0.001), eating discomfort (2.7 [1.7,3.0] vs. 3.3 [2.7,4.0 ], Z=3.393, P=0.001), and total symptoms (2.3 [1.7,2.7] vs. 2.5 [2.2,2.9], Z=2.243, P=0.025) than those in the gastric tube group; The scores for postoperative symptoms (2.0 [1.0,3.0] vs. 2.0 [2.0, 3.0], Z=2.127, P=0.033), meals consumed (2.0 [1.0, 2.0] vs. 2.0 [2.0, 3.0], Z=3.976, P<0.001), work (1.0 [1.0, 2.0] vs. 2.0 [1.0, 2.0], Z=2.279, P=0.023] and daily life (1.7 [1.3, 2.0] vs. 2.0 [2.0, 2.3], Z=3.950, P<0.001) were better in the PG-DT than the PG-GT group. Patients in the PG-GT group scored better than those in the PG-DT group for somatic symptoms, such as anal evacuation (3.0 [2.0, 4.0] vs. 3.5 [2.0, 5.0], Z=2.345, P=0.019). There were no significant differences in hemoglobin, serum albumin, serum total protein, or weight loss 1 year postoperatively between the two groups (all P>0.05). Conclusions: The safety of double tract anastomosis for proximal gastric cancer is comparable to that of gastric tube surgery. Compared with gastric tube surgery, double tract anastomosis achieves less esophageal reflux and better quality of life, making it a preferable surgical procedure for proximal gastric cancer.

[Study on the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A].

Objective: To summarize the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A. Methods: In the retrospective study, a total of 1 226 clinical isolates from suspected multidrug-resistant pulmonary tuberculosis patients in Beijing TB control system from 2016 to 2021 were identified as Mycobacterium tuberculosis (MTB) strains by MPB64 antigen detection test. Rifampicin-resistant tuberculosis (RR-TB) strains were screened by the phenotypic drug susceptibility using the proportion method. The drug susceptibilities of Levofloxacin(LFX), Moxifloxacin(MFX), Bedaquiline(BDQ) and Linezolid(LZD)were detected by the phenotypic drug susceptibility with microplate method. The drug resistance rate, drug resistance level and minimum inhibitory concentration (MIC) distribution of four anti-tuberculosis drugs in group A were analyzed. We calculated the demographic distribution of RR-TB, multidrug-resistant tuberculosis(MDR-TB), pre-extensively drug resistant tuberculosis (pre-XDR-TB), extensively drug resistant tuberculosis (XDR-TB) patients and the cross resistance of LFX and MFX, then summarized the drug-resistance spectrum of BDQ-resistant and LZD-resistant strains and the treatment outcome of RR-TB patients. Measurement data were expressed as rate or composition ratio,χ2 test was used between and within groups, and P<0.05 was considered statistically significant. Results: Among the 1 226 suspected multidrug-resistant pulmonary tuberculosis patients, the detection rates of RR/MDR/pre-XDR/XDR-TB patients were 20.8%(255/1 226), 15.2%(186/1 226), 5.7%(70/1 226), 0.5%(6/1 226), respectively. There were statistically significant differences in the distribution of patients with the four types of drug resistance in terms of age and treatment history (χ2=14.95, P=0.020;χ2=15.91, P=0.001). The drug resistance rates of LFX, MFX, BDQ and LZD in RR-TB patients were 27.5% (70/255), 27.5% (70/255), 0.4% (1/255) and 2.4% (6/255), respectively. The MICs of LFX, MFX and LZD-susceptible MTB were mainly at 0.25 mg/L, and the MIC of BDQ-susceptible MTB was mainly concentrated at 0.03 mg/L. 25.1% (64/255) of the RR MTB were resistant to both LFX and MFX, and 6 strains were resistant to LFX or MFX, showing incomplete two-way cross resistance. One BDQ-resistant strain and six LZD-resistant strains were detected. The treatment success rate of RR-TB patients was 74.4% (151/203), and there were statistically significant differences in treatment outcomes between resistant and sensitive patients on the LFX-containing treatment regimen (Fisher's exact test, P=0.012). Conclusions: The prevalence of fluoroquinolones (LFX and MFX) resistance in rifampicin-resistant MTB is very serious. LFX and MFX show incomplete bidirectional cross-resistance. BDQ and LZD have the most promising future in the treatment of MDR-TB. Improve drug-resistance testing will help to further improve the success rate of treatment.

Injectable systems for long-lasting insulin therapy.

Insulin therapy is the mainstay to treat diabetes characterizedd by hyperglycemia. However, its short half-life of only 4-6 min limits its effectiveness in treating chronic diabetes. Advances in recombinant DNA technology and protein engineering have led to several insulin analogue products that have up to 42 h of glycemic control. However, these insulin analogues still require once- or twice-daily injections for optimal glycemic control and have poor patient compliance and adherence issues. To achieve insulin release for more than one day, different injectable delivery systems including microspheres, in situ forming depots, nanoparticles and composite systems have been developed. Several of these delivery systems have advanced to clinical trials for once-weekly insulin injection. This review comprehensively summarizes the developments of injectable insulin analogs and delivery systems covering the whole field of injectable long-lasting insulin technologies from prototype design, preclinical studies, clinical trials to marketed products for the treatment of diabetes.

[Interpretation of Consolidated Health Economic Evaluation Reporting Standards 2022].

The number of studies related to health economics evaluation is increasing. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) contains 28 items. Based on CHEERS 2013, CHEERS 2022 adds a health economic analysis plan, model sharing, and community, patient, public, and other relevant stakeholders' participation in the statement, taking into account the future development direction of health economics evaluation. It provides a useful review tool for peer reviewers, editors, and readers and supports health technology assessment agencies in establishing standard reporting standards for health economics evaluations. In this study, we briefly introduced and interpreted the CHEERS 2022 statement and analyzed an example of health economics evaluation in infectious disease epidemiology to provide a reference for researchers to report studies regarding health economics evaluation standardly.

[Correlation between pelvic relapses of rectal cancer after radical and R0 resection: A regression model-based analysis].

Objective: To propose a new staging system for presacral recurrence of rectal cancer and explore the factors influencing radical resection of such recurrences based on this staging system. Methods: In this retrospective observational study, clinical data of 51 patients with presacral recurrence of rectal cancer who had undergone surgical treatment in the Department of Gastrointestinal Surgery, Peking University People's Hospital between January 2008 and September 2022 were collected. Inclusion criteria were as follows: (1) primary rectal cancer without distant metastasis that had been radically resected; (2) pre-sacral recurrence of rectal cancer confirmed by multi-disciplinary team assessment based on CT, MRI, positron emission tomography, physical examination, surgical exploration, and pathological examination of biopsy tissue in some cases; and (3) complete inpatient, outpatient and follow-up data. The patients were allocated to radical resection and non-radical resection groups according to postoperative pathological findings. The study included: (1) classification of pre-sacral recurrence of rectal cancer according to its anatomical characteristics as follows: Type I: no involvement of the sacrum; Type II: involvement of the low sacrum, but no other sites; Type III: involvement of the high sacrum, but no other sites; and Type IV: involvement of the sacrum and other sites. (2) Assessment of postoperative presacral recurrence, overall survival from surgery to recurrence, and duration of disease-free survival. (3) Analysis of factors affecting radical resection of pre-sacral recurrence of rectal cancer. Non-normally distributed measures are expressed as median (range). The Mann-Whitney U test was used for comparison between groups. Results: The median follow-up was 25 (2-96) months with a 100% follow-up rate. The rate of metachronic distant metastasis was significantly lower in the radical resection than in the non-radical resection group (24.1% [7/29] vs. 54.5% [12/22], χ2=8.333, P=0.026). Postoperative disease-free survival was longer in the radical resection group (32.7 months [3.0-63.0] vs. 16.1 [1.0-41.0], Z=8.907, P=0.005). Overall survival was longer in the radical resection group (39.2 [3.0-66.0] months vs. 28.1 [1.0-52.0] months, Z=1.042, P=0.354). According to univariate analysis, age, sex, distance between the tumor and anal verge, primary tumor pT stage, and primary tumor grading were not associated with achieving R0 resection of presacral recurrences of rectal cancer (all P>0.05), whereas primary tumor pN stage, anatomic staging of presacral recurrence, and procedure for managing presacral recurrence were associated with rate of R0 resection (all P<0.05). According to multifactorial analysis, the pathological stage of the primary tumor pN1-2 (OR=3.506, 95% CI: 1.089-11.291, P=0.035), type of procedure (transabdominal resection: OR=29.250, 95% CI: 2.789 - 306.811, P=0.005; combined abdominal perineal resection: OR=26.000, 95% CI: 2.219-304.702, P=0.009), and anatomical stage of presacral recurrence (Type III: OR=16.000, 95% CI: 1.542 - 166.305, P = 0.020; type IV: OR= 36.667, 95% CI: 3.261 - 412.258, P = 0.004) were all independent risk factors for achieving radical resection of anterior sacral recurrence after rectal cancer surgery. Conclusion: Stage of presacral recurrences of rectal cancer is an independent predictor of achieving R0 resection. It is possible to predict whether radical resection can be achieved on the basis of the patient's medical history.

[Indications and complications prevention and management of phaseâ ¡ implantation of Provox Vega voice prosthesis after total laryngectomy].

Objective: To explore the indications and management of common postoperative complications of phase II tracheoesophageal puncture (TEP) for Provox Vega voice prosthesis after total laryngectomy. Methods: The clinical data of 20 patients undergoing phase II TEP for Provox Vega voice prosthesis in our hospital between May 2021 and January 2022 were analyzed. Among them, there were 19 males and 1 female, aged from 37 to 76 years, with an average age of (60.0±8.4)years. The surgical indications and the prevention and treatment of common postoperative complications were summarized. Descriptive analysis was used in this research. Results: The basic surgical indications were as following: after total laryngectomy, there was no stenosis of the stoma and esophagus entrance, no scar constitution, no mouth opening restriction, no stiffness and backward restraint of the neck after radiotherapy, and more than half a year apart surgery or radiotherapy. Among the 20 patients, 18 underwent implantation successfuly, 1 failed in the operation, and for 1 patient, the prosthesis was removed due to bleeding 1 week after implantation. The common postoperative complications included TEP fistula infection (2 cases), the TEP fistula bleeding(1 case), deep neck (prevertebral) abscess (1 case), granulation at the inner side of the TEP fistula (1 case), invagination of the prosthesis (2 cases) and leakage around the prosthesis (2 cases). All patients were cured with different interventions. Conclusions: The Provox Vega voice prosthesis is generally safe for phase Ⅱ implantatione, but implantation indications need to be established. Common postoperative complications can be solved through preventive and remedial interventions.

HISMD: A Novel Immune Subtyping System for HNSCC.

Immune subtyping is an important way to reveal immune heterogeneity, which may contribute to the diversity of the progression and treatment in head and neck squamous cell carcinoma (HNSCC). However, reported immune subtypes mainly focus on levels of immune infiltration and are mostly based on a mono-omics profile. This study aimed to identify a comprehensive immune subtype for HNSCC via multi-omics clustering and build a novel subtype prediction system for clinical application. Data were obtained from The Cancer Genome Atlas database and our independent multicenter cohort. Multi-omics clustering was performed to identify 3 clusters of 499 patients in The Cancer Genome Atlas based on immune-related gene expression and somatic mutations. The immune characteristics and biological features of the obtained clusters were revealed by bioinformatics, and 3 immune subtypes were identified: 1) adaptive immune activation subtype predominantly enriched in T cells, 2) innate immune activation subtype predominantly enriched in macrophages, and 3) immune desert subtype. Subsequently, the clinical implications of each subtype were analyzed per clinical epidemiology. We found that adaptive immune activation showed better survival outcomes and had a similar response to chemotherapy with innate immune activation, whereas immune desert might be relatively resistant to chemotherapy. Moreover, a subtype prediction system was developed by deep learning with whole slide images and named HISMD: HNSCC Immune Subtypes via Multi-omics and Deep Learning. We endowed HISMD with interpretability through image-based key feature extraction. The clinical implications, biological significances, and predictive stability of HISMD were successfully verified by using our independent multicenter cohort data set. In summary, this study revealed the immune heterogeneity of HNSCC and obtained a novel, highly accurate, and interpretable immune subtyping prediction system. For clinical implementation in the future, additional validation and utility studies are warranted.

Sex-specific metabolic risk factors and their trajectories towards the non-alcoholic fatty liver disease incidence.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. This study examined sex-specific associations between NAFLD and metabolic factors and investigated the trajectory of risk factors. METHODS: We retrospectively investigated 16,140 individuals from Beijing Health Management Cohort. Univariate and multivariate time-dependent Cox regression analyses were performed to identify independent risk factors for new-onset NAFLD. The trajectory of risk factors was investigated using the latent growth curve model and growth mixture model. RESULTS: Over a median follow-up of 3.15 years, 2,450 (15.18%) participants developed NAFLD. The risk factors for NAFLD in men were increased body mass index (BMI); waist circumference (WC); triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), haemoglobin (Hb), and serum uric acid (SUA) levels; and platelet (PLT) count and decreased serum creatinine-to-body weight (sCr/bw) and high-density lipoprotein cholesterol (HDL-C) levels. In women, the risk factors were increased BMI, WC, and fasting plasma glucose (FPG), TG, LDL-C, SUA, white blood cell (WBC), and PLT and decreased sCr/bw and HDL-C levels. In addition, BMI, LDL-C, sCr/bw and PLT changing trajectories were associated with NAFLD in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends was associated with NAFLD risk in women. CONCLUSIONS: Development of NAFLD is associated with BMI, LDL-C, sCr/bw and PLT changing trajectories in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends are associated an increased risk of NAFLD in women. Deterioration of metabolic risk factors status can be a predictor of NAFLD many years before its occurrence.

A preliminary study of peripheral T-cell subsets in porokeratosis patients with MVK or MVD variants.

Background: Porokeratosis (PK) is considered a skin-specific autoinflammatory keratinization disease. Intriguingly, four causative genes of PK are in turn arranged in mevalonate pathway, with MVD variants being the commonest followed by MVK variants in a cohort of Chinese patients. Evidence indicates that mevalonate metabolites induce trained immunity in human monocytes and regulate T cells at multiple levels. Of note, γδT cells are dually regulated by intracellular and extracellular mevalonate metabolism. Aims: To identify the possible differences in T-cell between MVK or MVD variants from PK patients. Materials & Methods: Targeted exome sequencing and exonic CNV screening were performed in 26 patients with PK. Sanger sequencing was used to validate all identified variants. Among them, 22 patients were identified with MVK or MVD variants. PBMCs from 22 PK patients and 27 normal controls (NCs) were analysed by flow cytometry for the frequencies of T cells subsets, including IFN-γ-, and TNF-α-producing T cells. Results: There were 14 mutations identified in the 26 PK patients, including 6 novel mutations (MVK: c.118_226+1337dup, c.388_392delGATATinsC, c.613A>T, c.768G>C, and MVD: c.250C>T, c.988T>G). In contrast to NCs, significantly decreased frequencies of CD8+ and Vγ9Vδ2 T cells were observed in the PK patients with MVD variants. Moreover, it was found that dysregulated secretion of pro-inflammatory cytokines by T cells in both PK patients with MVK and MVD variants. Conclusions: Our findings enriched the Human Gene Mutation Databases and showed probable differences in peripheral T cells subsets between PK patients and controls.

[Effect of tourniquet on morphology and stiffness of quadriceps in patients receiving total knee arthroplasty: a randomized controlled trial].

Objective: To evaluate tourniquet effect on the morphology and stiffness of quadriceps in patients receiving total knee arthroplasty (TKA). Methods: Total of 80 patients with primary knee osteoarthritis receiving unilateral primary TKA from August 2020 to June 2021 in Peking University Third Hospital were enrolled in this randomized controlled trial. The patients were randomly divided into tourniquet group and non-tourniquet group (40 cases in each group). The study measured and compared postoperative thickness and stiffness of quadriceps, as well as circumference of the affected thigh in two groups. Results: There were 11 males and 29 females in tourniquet group, 9 males and 31 females in non-tourniquet group, with mean age of (69.1±5.1) years and (67.4±5.3) years, respectively. There was no significant difference in demographic information such as gender, age and BMI (all P<0.05). Postoperative thickness of quadriceps, stiffness of quadriceps and circumferenceï¼»x¯±s or M （Q1，Q3）］of the affected thigh in all patients were (2.76±0.69) cm, 25.20 (17.83, 32.90) m/s, 54.00 (51.13, 56.00) cm. These outcomes in tourniquet and non-tourniquet groupï¼»x¯±s or M （Q1，Q3）］were (2.78±0.76) cm and (2.73±0.61) cm, 24.00 (17.15, 33.13) m/s and 25.20 (18.68, 32.85) m/s, 54.00 (49.75, 55.00) cm and 54.50 (52.13, 57.53) cm, respectively; no significant deference was found in these indexes between the two groups (all P>0.05). Conclusion: Tourniquet has no significant effect on morphology and stiffness of quadriceps in patients undergoing TKA.

[Feasibility and perioperative safety of transoral robotic surgery with da Vinci Xi platform].

Objective: To explore the feasibility and perioperative safety of transoral robotic surgery with da Vinci Xi platform for pharyngolaryngeal tumors. Methods: A retrospective analysis was performed on 55 consecutive cases with resection of pharyngolaryngeal tumors by transoral robotic surgery with da Vinci Xi platform from July 27, 2020 to October 31, 2021 in the Department of Head and Neck Surgery, Fudan University Eye, Ear, Nose and Throat Hospital, including 44 males and 11 females, aged 25-79 years. There were 41 cases of oropharyngeal tumors, 9 cases of parapharyngeal space tumors, 2 cases of laryngeal tumors, 2 cases of hypopharyngeal tumors and 1 case of retropharyngeal space tumor. Operative time, intraoperative blood loss, postoperative hospital stay, perioperative tracheotomy, nasal feeding, hemorrhage and other complications were analyzed. Results: Of the 55 patients, 54 received resection of pharyngolaryngeal tumors by da Vinci robot through oral approach, and only 1 case of pyriform sinus carcinoma underwent a conversion to open surgery due to poor exposure of lower margin. The average surgical time for the patients with transoral robotic surgeries was 64.4 min, the average blood loss was 24.8 ml, the average postoperative hospital stay was 6.9 d, and the average oral feeding time was 11.1 d. Seventeen patients (30.9%) underwent preventive tracheotomy during surgery. Among 38 cases of laryngeal cancer, 28 underwent simultaneously neck dissection. No serious complications occurred in all patients during and after operation. The follow-up time was 1-15 months. Aside from 1 patient had a relapse 10 months after surgery, other patients had no recurrence or metastasis. Conclusion: Transoral robotic surgery with da Vinci Xi is safe, effective and minimally invasive for resection of pharyngolaryngeal tumors under reasonable indications.