High-Performance Dental Resins Containing a Starburst Monomer.

Dimethacrylate-based chemistries feature extensively as resin monomers in dental resin-based materials due to their distinguished overall performance. However, challenges endure, encompassing inadequate mechanical attributes, volumetric shrinkage, and estrogenicity. Herein, we first synthesized a novel resin monomer, 9-armed starburst polyurethane acrylate (NPUA), via the grafting-onto approach. Compared to the primary commercial dental monomer 2,2-bis [p-(2'-hydroxy-3'-methacryloxypropoxy) phenyl] propane (Bis-GMA) (with a viscosity of 1,174 ± 3 Pa·s and volumetric shrinkage of 4.7% ± 0.1%), the NPUA monomer achieves the lower viscosity (158 ± 1 Pa·s), volumetric shrinkage (2.5% ± 0.1%), and cytotoxicity (P < 0.05). The NPUA-based resins exhibit the higher flexural strength, flexural modulus, hardness, and hydrophobicity and lower volumetric shrinkage, water absorption, and solubility compared to the Bis-GMA (70 wt%)/TEGDMA (30 wt%) resins. The NPUA-based composites exhibit significantly higher flexural strength, flexural modulus, and hardness and lower volumetric shrinkage (171.4 ± 3.0 MPa, 12.6 ± 0.5 GPa, 2.0 ± 0.2 GPa, and 3.4% ± 0.2%, respectively) compared to the Bis-GMA group (120.3 ± 4.7 MPa, 9.4 ± 0.7 GPa, 1.5 ± 0.1 GPa, and 4.7% ± 0.2%, respectively; P < 0.05). This work presents a viable avenue for augmenting the physicochemical attributes of dental resins.

[Progress and controversy in minimally invasive approach to radical cholecystectomy for gallbladder cancer].

Surgical treatment is one of the most important forms of treatment in patients with gallbladder cancer. With the development of minimally invasive technology, the feasibility, safety and efficacy of minimally invasive approaches such as laparoscopic or robotic-assisted radical cholecystectomy for gallbladder cancer have received continuous attention.For patients with an early T-stage (Tis or T1a), laparoscopic simple cholecystectomy is safe and economical, with a good prognosis for postoperative patients, and it has been widely accepted and performed. Radical resection of advanced gallbladder cancer requires resection of the gallbladder, its liver bed, and other neighboring invaded organs, as well as clearance of regional lymph nodes, which requires experienced gallbladder cancer treatment teams to strictly grasp the indications, select appropriate patients, and formulate a good surgical strategy to ensure the therapeutic effect. Meanwhile, robot-assisted radical resection for gallbladder cancer has been performed in a few centers and shows good clinical potential, but more high-quality studies are needed to further evaluate its value in gallbladder cancer treatment.

[Clinical application of a novel separated magnetic controlled forceps assisted single-incision laparoscopic cholecystectomy].

Objective: To explore the application value of a novel separated magnetic-controlled forceps in transumbilical single-incision laparoscopic cholecystectomy (SILC). Methods: This is a prospective case series study. Data from patients who underwent SILC at the Department of General Surgery, the Second Affiliated Hospital of Air Force Medical University from March to August 2023 were prospectively collected, based on inclusion and exclusion criteria. All patients underwent cholecystectomy assisted by a novel separated magnetic-controlled forceps. Surgical time, intraoperative blood loss, the need for additional incisions during surgery, and the length of hospital stay were recorded to assess surgical difficulty and effectiveness. Postoperative pain scores and complications were documented to evaluate the safety of the procedure. The collaboration experience of the surgeon and assistant was evaluated using a 5-point Likert scale to assess the feasibility of this surgical approach. Informed consent was obtained from all patients in accordance with medical ethical regulations. Patients were followed up through outpatient visits or telephone calls, with follow-up at 7 days and 1 month after surgery, and evaluation of incisional scar healing and completion of satisfaction questionnaires. Follow-up was conducted until September 30, 2023. Results: A total of 45 patients were included in the study,including 19 males and 26 females,aged (42.7±21.2)years(range:32 to 61 years). The difficulty of the operation was evaluated as grade 1 or 2 in 38 cases(84.4%) and grade 3 in 7 cases(15.6%). Operation time was (37.3±15.3) minutes(range: 25 to 80 minutes),and intraoperative blood loss(M(IQR)) was 17.8(35.0) ml (range:10 to 60 ml). All surgical procedures proceeded smoothly without intraoperative incidents, and the overall satisfaction of the surgeon and assistants was high. All patients underwent successful day surgery management and were discharged within 48 hours of hospitalization. The postoperative pain scores at 1, 7, and 30 days were 3 (4), 1 (4), and 0, respectively. The follow-up time was 5.0(1.8) weeks (range: 3 to 7 weeks), with no occurrence of grade 3 to 4 adverse reactions, and the patients were satisfied with the cosmetic effect of the umbilical incision. Conclusions: The novel separated magnetic-controlled forceps can be applied in transumbilical SILC. It has the advantages of convenient operation, and patients are satisfied with the surgical results.

[Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions (1): to improve the validity of real-world evidence].

Objective: Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect. Methods: Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results: Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap. Conclusion: Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

[Genome-wide Mendelian randomization study of the pathogenic role of gut microbiota in benign biliary tract diseases].

Objective: To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization. Methods: This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests. Results: Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95%CI:0.80 to 0.97,P=0.012) and cholecystitis (IVW OR=0.88,95%CI:0.80 to 0.97,P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95%CI:1.02 to 1.30,P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95%CI: 1.08 to 2.04,P=0.016) and cholecystitis (IVW OR=1.17, 95%CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95%CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95%CI:1.02 to 1.13,P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95%CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95%CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95%CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95%CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95%CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions: Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.

[Suggestions on prevention throughout whole life cycle to curb the rapidly increasing prevalence of noncommunicable diseases in the population].

Chronic non-communicable diseases (NCDs) have become diseases that seriously threaten the health and quality of life of the Chinese population, and also become a major public health problem affecting the national economic and social development. With the intensification of China's population aging, the economic burden caused by NCDs will further increase. More and more evidence has shown that NCDs could be prevented, and the prevention and control of NCDs have been considered as a core task of building a healthy China. Therefore, precise personalized nutrition and the prevention of NCDs from the age of zero, which is called the "Double Zero Strategy", would provide a well-consolidated basis for body tissue structure, and prevention of NCDs should also begin at age zero, and then extend to the first 1 000 days of life. The "Double Zero Strategy" preventive intervention can improve the nutritional status, balance diet and nutrition, and increase physical activity among children, adolescents, adults, and the elderly, all of which can reduce the risk of chronic disease, disability, and death. Therefore, launching the "Double Zero Strategy" for full life cycle prevention will help to achieve China's health goals in the new era, and provide more comprehensive measures and plans for implementing the goal of a healthy China.

Enhanced Bonding to Caries-Affected Dentin Using an Isocyanate-Based Primer.

Dental caries is the most common oral disease and the most common cause of resin restorations. In minimally invasive dentistry, the principle behind cavity preparation is to remove external caries-infected dentin (CID) and preserve internal caries-affected dentin (CAD) and sound dentin (SD). The cavity floor is mainly composed of CAD, but the poor bonding performance of CAD has become a widespread concern. This study evaluated the performance of a new collagen-reactive monomer (ITCM) used as a primer to improve the bonding performance of CAD. The experimental specimens were grouped as follows: SD, CAD, and ITCM-pretreated CAD (CAD-ITCM). Dentin slices were obtained for attenuated total reflectance-Fourier transform infrared (ATR-FTIR) analysis. The bonded samples were subjected to microtensile bond strength analysis after 24 h of water storage or aging by thermocycling, and the bonding interface quality was evaluated by nanoleakage assessment, interfacial nanoindentation testing, and in situ zymography. Cytotoxicity experiments with ITCM were performed. ATR-FTIR showed that the isocyanate groups in ITCM can covalently bind and form hydrogen bonds with the collagen in CAD to mediate chemical bonding. ITCM pretreatment significantly improved the bond strength of CAD (P < 0.05), reduced interfacial nanoleakage, improved the sealing of the bonding interface, enhanced the homogeneity of the hybrid layer, and inhibited matrix metalloproteinase activity. In addition, ITCM presented acceptable biocompatibility for dental restorative application. Taken together, this study reported the application of ITCM to induce collagen-based chemical bonding in the CAD bonding system, which fills the gap in strategies to improve the bonding performance of CAD immediately and after aging and has important clinical application prospects.

[Comparison of two child growth standards in assessing the nutritional status of children under 6 years of age].

Objective: To compare the application of China growth standard for children under 7 years of age (China standards) and World Health Organization child growth standards (WHO standards) in evaluating the prevalence of malnutrition in children aged 0-<6 years in China. Methods: The research data came from the national special program for science & technology basic resources investigation of China, named "2019-2021 survey and application of China's nutrition and health system for children aged 0-18 years". Multi-stage stratified random sampling was used to recruit 28 districts (regions) in 14 provinces, autonomous regions or municipalities across the country. Children (n=38 848) were physically measured and questionnaires were conducted in the guardians of the children. The indicators of stunting, underweight, wasting, overweight and obesity were evaluated by China standards and WHO standards respectively. Chi-square test was used to comparing the prevalence of each nutritional status between the two standards, as well as the comparison between the two standards by gender and age. Results: Among the 38 848 children, 19 650 were boys (50.6%) and 19 198 were girls (49.4%), 19 480 urban children (50.1%) and 19 368 rural children (49.9%). The stunting, underweight and wasting cases in the study population were 2 090 children (5.4%), 1 354 children (3.5%) and 1 276 children (3.3%) according to the China standards, and 1 474 children (3.8%), 701 children (1.8%) and 824 children (2.1%) according to the WHO standards, respectively; the above rates according to the China standards were slightly higher than those to the WHO standards (χ2=111.59, 213.14, and 99.99, all P<0.001). The overweight and obesity cases in the study population were 2 186 children (5.6%) and 1 153 children (3.0%) according to the China standards, and 2 210 children (5.7%) and 1 186 children (3.1%) according to the WHO standards, with no statistically significant differences (χ2=0.14 and 0.48, P=0.709 and 0.488, respectively). Compared to the results based on WHO standards, the China standards showed a lower prevalence of overweight and obesity in boys (χ2=14.95 and 5.85, P<0.001 and =0.016, respectively), and higher prevalence of overweight in girls (χ2=12.60, P<0.001); but there was no statistically significant differences in girls' obesity prevalence between the two standards (χ2=2.62, P=0.106). Conclusions: In general, the prevalence of malnutrition among children aged 0-<6 years based on China standards is slightly higher than that on WHO standards. To evaluate the nutritional status of children, it is advisable to select appropriate child growth standards based on work requirements, norms or research objectives.

[Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis].

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.

Hemorrhagic risk factors after rt PA thrombolysis in acute cerebral infarction.

OBJECTIVE: This study aims to investigate the risk factors of hemorrhagic transformation (HT) after thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute cerebral infarction (ACI) and establish a logistic regression equation and the risk prediction model. PATIENTS AND METHODS: One hundred and ninety patients with ACI were divided into the HT group (n=20) and non-HT group (n=170) according to whether HT occurred within 24 hours after rt-PA thrombolysis. The clinical data were collected for analyzing the influencing factors, and a logistic regression analysis model was then established. Besides, patients in the HT group were further grouped into symptomatic hemorrhage (n=7) and non-symptomatic hemorrhage (n=13) according to the type of hemorrhage. The clinical diagnostic value of risk factors in symptomatic hemorrhage after thrombolysis in ACI was analyzed using the ROC curve. RESULTS: We found that history of atrial fibrillation, time from onset to thrombolysis, pre-thrombolytic glucose, pre-thrombolytic National Institute of Health Stroke Scale (NIHSS) score, 24-hour post-thrombolytic NIHSS score, and proportion of patients with large cerebral infarction were all the influencing factors of HT risk after rt-PA thrombolysis in patients with ACI (p<0.05). Logistic regression analysis model was established with an accuracy of 88.42% (168/190), a sensitivity of 75.00% (15/20), and a specificity of 90.00% (153/170). The time from onset to thrombolysis, pre-thrombolytic glucose, and 24-hour post-thrombolytic NIHSS score had higher clinical value in predicting the risk of HT after rt-PA thrombolysis, with the AUCs of 0.874, 0.815 and 0.881, respectively. Blood glucose and pre-thrombolytic NIHSS score were independent risk factors related to symptomatic hemorrhage after thrombolysis in ACI (p<0.05). The AUCs for predicting symptomatic hemorrhage alone and in combination were 0.813, 0.835, and 0.907, respectively, with sensitivities of 85.70%, 87.50% and 90.00%, and specificities of 62.50%, 60.00%, and 75.42% respectively. CONCLUSIONS: The establishment of a prediction model based on the risk factors of HT after rt-PA thrombolysis had a good predictive value in patients with ACI. This model was helpful in guiding clinical judgment and improving the safety of intravenous thrombolysis. Early identification of symptomatic bleeding risk factors provided a reference for clinical treatment and prognostic measures of patients with ACI.

[Global liver cancer incidence and mortality and future trends from 2000 to 2020: GLOBOCAN data analysis].

Objective: To compare the geographical differences and time trends of liver cancer incidence and mortality in different regions around the world so as to predict the future burden of liver cancer. Methods: The incidence and mortality data of liver cancer in different Human Development Index (HDI) countries from 2000 to 2020 were collected from the GLOBOCAN 2020 database. The joinpoint model and annual percent change (APC) were used to analyze the liver cancer global incidence and mortality as well as future epidemic trends from 2000 to 2020. Results: ASMR for male liver cancer was increased from 8.0/100, 000 in 2000 to 7.1/100,000 in 2015 (APC = -0.7, 95%CI: -1.2 ~ -0.3, P = 0.002), while ASMR for female liver cancer was increased from 3.0/100, 000 in 2000 to 2.8/100, 000 in 2015 (APC = -0.5, 95%CI: -0.8 ~ -0.2, P < 0.001). The ratio of male to female ASMR was 2.67:1 in 2000 and 2.51:1 in 2015, indicating a slight narrowing of the difference in mortality between men and women. In 2020, the global ASIR and ASMR for liver cancer were 9.5/100 000 and 8.7/100 000, respectively. Male ASIR and ASMR (14.1/100, 000 and 12.9/100, 000, respectively) were 2 ~ 3 times higher than females (5.2/100, 000 and 4.8/100, 000, respectively). There were significant differences between ASIR and ASMR in different HDI countries and regions (P(ASIR) = 0.008, P(ASMR) < 0.001), and the distributions of ASMR and ASIR were very similar. New cases and deaths were expected to increase by 58.6% (143,6744) and 60.9% (133, 5 375) in 2040, with the number of cases and deaths increasing by 39,7003 and 37,4208 in Asia, respectively. Conclusion: ASMR due to liver cancer worldwide has had a downward trend between 2000 and 2015. However, the latest epidemiological status and predictions of liver cancer in 2020 indicate that prevention and control will still be a major challenge globally in the next 20 years.

[Landscape and metastases of the lymph nodes in prostatic anterior fat pad at radical prostatectomy].

Objectives: To examine the landscape and metastases of the lymph nodes in prostatic anterior fat pad (PAFP) at radical prostatectomy (RP), and to describe the clinical characteristic of the patients with lymph node metastases in PAFP. Methods: The clinical and pathological data of 287 prostate cancer patients underwent RP from December 2019 to August 2021 in Department of Urology, Sun Yat-sen University Cancer Center were collected and analyzed retrospectively. All patients were male, aging (66±7) years (range: 42 to 83 years). The preoperative prostate-specific antigen (PSA) (M(IQR)) were 16.00(29.64) µg/L (range: 0.01 to 99.90 µg/L). There were 244 patients with localized or locally advanced prostate cancer and 43 patients with metastatic prostate cancer. All PAFP were dissected at RP routinely and were sent for pathologic analysis respectively. The PAFP was dissected from the prostate apex caudally toward the bladder neck and dissection extended to the joint of the prostate and the endopelvic fascia bilaterally. All the specimen of PAFP were examined and reported by subspecialty pathologists of genitourinary tumors. Statistical analysis was performed by Student t test, Wilcoxon rank-sum test, χ2 test or Fisher exact test. Results: There were 8.0% (23/287) patients with lymph nodes in PAFP, 3.8% (11/287) patients with PAFP lymph node metastases. Pathologically upstaged occurred in 1 patient due to the PAFP lymph node as the solitary metastatic lesion. Patients with lymph node metastases in PAFP presented higher preoperative PSA (M(IQR): 48.2(73.0) µg/L vs. 15.4(26.5) µg/L, Z=3.158, P=0.002), clinical T stage and N stage (Z=2.977, P=0.003; Z=2.780, P=0.005) and preoperative Gleason score (Z=2.205, P=0.027). Conclusions: Routine dissection of PAFP at RP and separately pathological analysis may allow more lymph nodes and lymph node metastases detection. More accurate pathological N stage may be acquired and consequently may improve the survival of patients by offering more appropriate adjuvant or salvage therapy.

Abnormal hyperplasia of chondrocytes in a rat model of glucocorticoid-induced osteonecrosis of the femoral head.

OBJECTIVE: The aim of our study was to determine whether abnormal hyperplasia of chondrocytes occurs in glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) using a well-established rat model. MATERIALS AND METHODS: Rats were injected with lipopolysaccharide and methylprednisolone to induce GC-ONFH, while control animals were injected with saline (12 animals per group). Establishment of the disease model was confirmed using micro-computed tomography and hematoxylin-eosin (HE) staining of femoral head tissue sections. Chondrocyte hyperplasia was detected using HE staining and semi-quantitated using toluidine blue and saffron O staining. Expression of the autophagy marker LC3B was assessed in cartilage tissues of femoral head using immunohistochemistry. RESULTS: GC-ONFH animals showed significantly greater area of abnormal chondrocyte hyperplasia in femoral head tissue sections than control animals. They also showed significantly higher expression of LC3B in articular cartilage of the femoral head. CONCLUSIONS: GC-ONFH may be associated with abnormal chondrocyte hyperplasia in articular surface cartilage, which may be related to glucocorticoid-induced overactivation of autophagy.

[The role of gut microbiota dysbiosis in the occurrence and development of inflammatory bowel disease and its prevention and control strategies].

The occurrence of inflammatory bowel disease (IBD) is related to environmental factors, host immune status, genetic susceptibility and flora imbalance. With the development of sequencing technologies, the relationship between intestinal microbiota and IBD has been further studied and confirmed in many aspects. This article summarizes the characteristics of microbiota alterations in patients with IBD, as well as the role and mechanisms of microbiota dysbiosis in the onset and development of IBD, and discusses the research status of therapies based on intestinal microbiota, prospecting the future of intestinal flora in the prevention, diagnosis, treatment and prognosis of IBD.

[Progress in clinical diagnosis and treatment of gallbladder cancer].

Due to the lack of effective early diagnosis and treatment, gallbladder cancer(GBC) remains a malignant tumor with extremely high malignancy and poor prognosis. Therefore, high quality studies are required to break through the bottleneck in GBC diagnosis and treatment. This article reviewed the domestic and foreign GBC research published in 2021, presenting a comprehensive summary of the important advances in the field of clinical diagnosis and treatment. Latest epidemiological data and risk factors, emerging diagnostic methods of peripheral blood laboratory tests and imaging, new pathologic classification system, hot topics and controversies of surgical treatment as well as the dynamics of systemic treatment of GBC are reviewed in the article. The present findings may contribute to a more efficient means of diagnosis and treatment for GBC and hold the promise of improved outcomes for patients with GBC.

[Effects of parity on nutrition and health status of Chinese women of childbearing age].

Objective: To analyze effects of parity on women's nutrition and health status. Methods: This study was based on the data bank of "Chinese Nutrition and Health Surveillance of Children and Adolescents Aged 0-17 years old and Lactating Mothers from 2016 to 2017". Using a multi-stage stratified random sampling method, 17 771 women at 0 to 24 months postpartum from 31 provinces in Mainland China were included in this study. Questionnaires were used to collect data on women's general demographic characteristics, parity, mode of delivery, pre-pregnancy weight, pre-delivery weight, diseases before and during pregnancy, postpartum hemorrhage. Current body height, body weight, waist circumference, and blood pressure were measured. Blood hemoglobin, blood glucose and blood lipids were detected. Pre-pregnancy BMI, gestational weight gain, postpartum weight retention, postpartum BMI, the rates of anemia, hypertension, diabetes, and dyslipidemia were calculated. Survey sample weights were calculated according to the sampling design and number of children under 2 years old from the sixth population census data of China. Effects of parity on the observational indicators after adjusting for confounding factors were analyzed by multivariate linear regression and multivariate logistic regression. Results: The age of 17 771 women was (29.5±5.0) years old, 12.2% (2 172) were over 35 but less than 40 years old, and 3.2% (563) were over 40 years old; the women with one parity, two parities, and three parities accounted for 47.3% (8 413), 48.5% (8 620) and 4.2% (738), respectively; urban women accounted for 49.9% (8 875), and rural women accounted for 50.1% (8 896). The results from multivariate linear regression showed that the pre-pregnancy BMI of women with two and three parities was 0.55 kg/m2 and 0.76 kg/m2 higher than women with one parity, respectively; the results of multivariate logistic regression showed that the OR(95%CI) of pre-pregnancy anemia was 1.45(1.04-2.02) for women with three parities compared with women with one parity, and the OR(95%CI) of anemia during pregnancy for women with two parities was 1.20(1.06-1.35) compared with women with one parity. Conclusion: Parity is associated with pre-pregnancy BMI and risk of anemia before and during pregnancy in women of reproductive age.

Quantitative systems pharmacology modeling sheds light into the dose response relationship of a trispecific T cell engager in multiple myeloma.

In relapsed and refractory multiple myeloma (RRMM), there are few treatment options once patients progress from the established standard of care. Several bispecific T-cell engagers (TCE) are in clinical development for multiple myeloma (MM), designed to promote T-cell activation and tumor killing by binding a T-cell receptor and a myeloma target. In this study we employ both computational and experimental tools to investigate how a novel trispecific TCE improves activation, proliferation, and cytolytic activity of T-cells against MM cells. In addition to binding CD3 on T-cells and CD38 on tumor cells, the trispecific binds CD28, which serves as both co-stimulation for T-cell activation and an additional tumor target. We have established a robust rule-based quantitative systems pharmacology (QSP) model trained against T-cell activation, cytotoxicity, and cytokine data, and used it to gain insight into the complex dose response of this drug. We predict that CD3-CD28-CD38 killing capacity increases rapidly in low dose levels, and with higher doses, killing plateaus rather than following the bell-shaped curve typical of bispecific TCEs. We further predict that dose-response curves are driven by the ability of tumor cells to form synapses with activated T-cells. When competition between cells limits tumor engagement with active T-cells, response to therapy may be diminished. We finally suggest a metric related to drug efficacy in our analysis-"effective" receptor occupancy, or the proportion of receptors engaged in synapses. Overall, this study predicts that the CD28 arm on the trispecific antibody improves efficacy, and identifies metrics to inform potency of novel TCEs.

[The clinical value of oral robotic surgery in the treatment of oropharyngeal squamous cell carcinoma].

Objective: To explore the therapeutic effects of transoral robotic surgery (TORS) and traditional surgical modes in oropharyngeal squamous cell carcinoma (OPSCC). Methods: The clinicopathological data of patients with oropharyngeal squamous cell carcinoma treated at Sun Yat-sen University Cancer Center from 2010 to 2018 were retrospectively analyzed. 135 cases were treated with traditional surgery (non-TORS group), while 52 cases were treated with TORS (TORS group). The prognosis of the two groups of patients were analyzed by Kaplan-Meier method and Log rank test, the influencing factors were analyzed by Cox regression model. Results: The 2-year overall survival (OS, 94.2%) and 2-year progression-free survival (PFS, 93.8%) of patients in the TORS group were better than those in the non-TORS group (71.4% and 71.4%, respectively, P<0.05). The 2-year OS (93.3%) and 2-year PFS (92.8%) of TORS group patients in T1-2 stage were better than those of non-TORS group (73.1% and 72.8%, respectively, P<0.05). The 2-year OS (95.8%) and 2-year PFS (95.2%) of patients with stage Ⅰ to Ⅱ in the TORS group were not significantly different from those in the non-TORS group (84.1% and 83.9%, respectively, P>0.05). The 2-year OS (92.9%) and 2-year PFS rate (92.7%) of patients with stage Ⅲ to Ⅳ in the TORS group were better than those in the non-TORS group (64.7% and 63.9%, respectively, P<0.05). The 2-year OS (94.4%) of HPV-positive patients in the TORS group was not significantly different from that in the non-TORS group (83.3%, P=0.222). The 2-year OS of HPV-negative patients in the TORS group (94.1%) was significantly different from that in the non-TORS group (43.7%, P<0.001). HPV status was an independent prognostic factor (P=0.008). Conclusions: TORS has a better prognosis in the treatment of oropharyngeal squamous cell carcinoma compared with the traditional treatment methods. The patients with T1-T2 can achieve better survival benefits after TORS treatment. The HPV-positive OPSCC patients has a better prognosis than that of HPV-negative OPSCC patients, and regardless of HPV status, OPSCC patients in the TORS group could obtain a better survival prognosis.

[Pay close attention to the current characteristics and development trend of severe acute hepatitis with unknown etiology in children worldwide].

In the past, acute hepatitis of unknown etiology in children was sporadic. However, during the last three weeks, there has been a trend of short-term outbreak around the world. As of May 3, 2022, at least 228 cases had been reported in about 20 countries and regions. The main clinical manifestations of the children included abdominal pain, diarrhea, vomiting, jaundice, and hepatomegaly. The liver functions including alanine aminotransferase and total bilirubin increased sharply. About 8.8% of the children needed liver transplantation. The etiology is not clear, but adenovirus type 41 is currently considered to be the most likely cause. Clinicians should keep alert to acute hepatitis of unknown etiology in children, strengthen epidemic surveillance, clinical treatment, and carry out necessary health education.

[Retropharyngeal lymph node dissection in head and neck cancers treated with transoral robotic surgery].

Objective: To evaluate the indications, safety, feasibility, and surgical technique for patients with head and neck cancers undergoing transoral robotic retropharyngeal lymph node (RPLN) dissection. Methods: The current study enrolled 12 consecutive head and neck cancer patients (seven males and four females) who underwent transoral robotic RPLN dissection with the da Vinci surgical robotic system at the Sun Yat-sen University Cancer Center from May 2019 to July 2020. Seven patients were diagnosed as nasopharyngeal carcinoma with RPLN metastasis after initial treatments, 4 patients were diagnosed as thyroid carcinoma with RPLN metastasis after initial treatments, and one patient was diagnosed as oropharyngeal carcinoma with RPLN metastasis before initial treatments. The operation procedure and duration time, intraoperative blood loss volume and complications, nasogastric feeding tube dependence, tracheostomy dependence, postoperative complications, and hospitalization time were recorded and analyzed. Results: All patients were successfully treated by transoral robotic dissection of the metastatic RPLNs, none of which was converted to open surgery. RPLNs were completely resected in 10 patients, and partly resected in 2 patients (both were nasopharyngeal carcinoma patients). The mean number of RPLN dissected was 1.7. The operation duration time and intraoperative blood loss volume were (191.3±101.1) min and (150.0±86.6) ml, respectively. There was no severe intraoperative complication such as massive haemorrhage or adjacent organ injury during surgery. Nasogastric tube use was required in all patients with (17.1±10.6) days of dependence, while tracheotomy was performed in 8 patients with (11.6±10.7) days of dependence. The postoperative hospitalization stay was (8.5±5.7) days. Postoperative complications occurred in 4 patients, including 2 of retropharyngeal incision and 2 of dysphagia. During a follow-up of (6.5±5.1) months, disease-free progression was observed in all patients, 10 patients were disease-free survival and other 2 patients were survival with tumor burden. Conclusions: The transoral robotic RPLN dissection is safety and feasible. Compared with the traditional open surgical approach, it is less traumatic and safer, has fewer complications and good clinical application potentiality. The indications for transoral robotic RPLN dissection include thyroid carcinoma, oropharyngeal carcinoma, and some selected nasopharyngeal carcinoma and other head and neck cancers. Metastatic RPLNs from some nasopharyngeal carcinoma with incomplete capsule, unclear border and adhesion to the surrounding vessels are not suitable for transoral robotic RPLN dissection.