The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Objective:Based on the needs of advanced nursing practice development, to establish an indicator system of role function of position of oncology genetic nurses suitable for our national condition, and to provide a basis for position establishing of nocology genetic nurses.Methods:Initial indexes were generated through the literature review and semi-structured interviews. From September to December 2022, two rounds of expert consultations and analytic hierarchy process were conducted to establish the evaluation index for role function of position of oncology genetic nurses.Results:A total of 43 experts were included in the study, the response rates of 2 rounds were 93.62%(44/47) and 97.73%(43/44), and the authority coefficients of the experts were 0.821 and 0.853. The Kendall′s coefficients of concordance for the 2 rounds of consultations were 0.100-0.150 (all P<0.01) and 0.101-0.237 (all P<0.01). Finally, the role function system of position for oncology genetic nurses was formed, which consisted of 5 first-level indexes, 17 second-level indexes and 86 third-level indexes. Conclusions:The system of role function of position for oncology genetic nurses is reasonable, scientific and reliable, professional and specific, which can provide a theoretical reference for the development of advanced nursing practice on hereditary oncology in China.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Non-alcoholic fatty liver disease (NAFLD), as a metabolic disease, has shown a constant upward trend in prevalence among the people in recent years. In addition to changing lifestyles and conventional drug treatment, bariatric surgery, represented by Roux-en-Y gastric bypass surgery and sleeve gastrectomy, has gradually become one of the treatment options for NAFLD. However, the mechanism of bariatric surgery in treating NAFLD remains to be studied. The "multiple-hit theory", which has gradually been recognized in recent years, believes that NAFLD is formed by the combined effect of multiple mechanisms such as insulin resistance, bile acid metabolism pathway, and intestinal flora. Based on relevant literatures and clinical practices, the authors explore the relevant mechanisms of bariatric surgery for direct or indirect treatment of NAFLD.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:To investigate the iodine nutrition status of residents and its changing trend in Baoji City, Shaanxi Province during the 10 years implementation of a new salt iodine standard, evaluate the prevention and treatment effects, and provide a basis for implementing iodine supplementation measures scientifically.Methods:From 2013 to 2015, each county (district) in Baoji City, Shaanxi Province was divided into 5 districts based on east, west, south, north, and central regions. One town (street, referred to as the town) was selected from each district, and four administrative villages were selected from each town. Fifteen residents from each administrative village were selected to collect edible salt samples from their homes and test the iodine content of the salt. At the same time, one primary school was selected from each selected town, and 42 children (age and gender were balanced) aged 8 - 10 were selected from each primary school for thyroid palpation examination. From 2016 to 2022, each county (district) was divided into 5 districts based on east, west, south, north, and central regions. One town was selected from each district, and one primary school was selected from each town. Forty-two non boarding students aged 8 - 10 were selected from each primary school to undergo thyroid palpation examination, and edible salt samples were collected from their home to detect salt iodine content. At the same time, 4 administrative villages were selected from each town, and 10 households were selected from each administrative village to collect edible salt samples and test the salt iodine content; 21 pregnant women were selected from each of the 5 towns in each county (district) to collect edible salt samples and test the salt iodine content. From 2013 to 2022, synchronous collection of urine samples from children and pregnant women (early, middle, and late pregnancy were balanced) was conducted to detect urine iodine content. Direct titration method was adopted for determination of salt iodine content, and arbitration method was adopted for Sichuan salt and other fortified edible salt (GB/T 13025.7-1999). Thyroid examination was performed according to the Diagnostic Criteria for Endemic Goiter (WS 276-2007). Urine iodine was detected by Arsenic Cerium Catalytic Spectrophotometric Method for Determination of Iodine in Urine (WS/T 107 - 2006).Results:From 2013 to 2022, a total of 37 609 household edible salt samples were collected. The coverage rate of iodized salt, the qualified rate of iodized salt and the consumption rate of qualified iodized salt for each year ranged from 98.00% to 100.00%, 94.16% to 99.55%, and 92.28% to 99.67%, respectively. The median range of salt iodine was 22.42 to 26.80 mg/kg. A total of 25 437 children aged 8 - 10 were examined, and the annual incidence of thyroid enlargement (goiter) ranged from 0.35% to 3.02%. A total of 33 270 urine samples were collected, including 21 698 from children and 11 572 from pregnant women. The median range of urine iodine for children in each year was 203.70 - 275.47 μg/L, median range of urine iodine in pregnant women was 167.65 - 218.57 μg/L. The median urine iodine in children showed a decreasing trend from 2013 to 2022 ( Z = 3.04, P = 0.002); the median urine iodine of pregnant women did not show a significant decrease ( Z = 1.61, P = 0.110). Conclusions:During the 10 years implementation of the new salt iodine standard in Shaanxi Province, all indicators of iodine deficiency disorders monitoring in Baoji City have met the standards and maintained the elimination status of iodine deficiency disorders. The urine iodine levels of children have shown a downward trend, while urine iodine levels of pregnant women do not show significant changes. It is recommended that Baoji City expand the scope of iodine nutrition monitoring for key populations, and effectively carry out iodine supplementation measures scientificlly guided by monitoring information, tailored to local conditions, and classified guidance.

Objective:To investigate the risk factors of postoperative continuous renal replacement therapy application in Stanford type A acute aortic dissection.Methods:This retrospective study included 527 patients with Stanford type A acute aortic dissection from November 2015 to February 2018 in Beijing Anzhen Hospital. They were divided into 2 groups according to whether or not needed postoperative continuous renal replacement therapy, group CRRT(78 cases) and group None CRRT(449 cases). Binary logistic regression analysis was used to analyze the risk factors of continuous renal replacement therapy. Results:Of all the patients, the percentage of using continuous renal replacement therapy was 14.8%(78/527), and the mortality of 30 days after surgery was 8.5%(45/527). The independent risk factors associated with CRRT were preoperative serum creatinine(sCr)( OR=1.012, 95% CI: 1.005-1.019, P<0.001), transfusion of red blood cell in surgery( OR=1.141, 95% CI: 1.071-1.216, P<0.001), transfusion of platelet in surgery( OR=1.307, 95% CI: 1.084-1.576, P=0.005), the total amount of drainage( OR=1.000, 95% CI: 1.000-1.000, P=0.036), and the time of extubation after surgery( OR=1.004, 95% CI: 1.001-1.008, P=0.013). Conclusion:The risk factors of CRRT after emergency surgery of Stanford type A acute aortic dissection are preoperative serum creatinine, transfusion of red blood cell in surgery, transfusion of platelet in surgery, the total amount of drainage and the time of tracheal extubation after surgery. We need to focus on those risk factors in our daily job and manage them timely and properly, in order to improve patients’ prognosis.

Objective:To explore the effect of constructing WeChat platform and introducing PPT (PowerPoint) optimized by Media studio pro editing technology in the teaching of radiation therapeutics.Methods:Sixty undergraduates of medical imaging technology in Fujian Medical University were randomly divided into experimental group and control group in average. The experimental group set up a WeChat group and acquired the optimized PPT before class; control group received classroom teaching and clinical practice according to the traditional teaching mode. Twenty-four items of MCTQ (Maastricht clinical teaching questionnaire) were selected and translated. A total of 30 teachers majoring in tissue radiation oncology and medical imaging were randomly divided into two groups. The questionnaire was used to evaluate the two teaching models. To examine the academic performance of the two groups of students. SPSS 23.0 software was used for independent sample t-test. Results:By comparing the scores of MCTQ questionnaire between the two groups, it was concluded that the teaching mode of the experimental group had significant advantages in 11 aspects, such as clinical practice, obtaining more learning opportunities and so on ( P < 0.05). The scores of practice [(84.67±7.29) vs. (80.03±8.97)] and final evaluation [(81.53±8.78) vs. (76.77±9.49)] of the students in the experimental group were better than those in the control group ( P < 0.05). Conclusion:The application of optimized PPT by Media studio pro editing technology based on WeChat platform is worth popularizing in the teaching of radiation therapeutics.

Objective:To analyze the surgical types of patients with Kashin-Beck disease (KBD) in Shaanxi Province, and to provide reference for optimizing KBD surgery.Methods:Retrospective analysis was used to investigate KBD patients who underwent surgical treatment, and the patient's information was from the Shaanxi Provincial Endemic Disease Prevention and Control Information System. Patients with incomplete surgical treatment information were excluded, and χ 2 test was used to analyze the impact of factors such as gender, education level, living area, disease severity, and social environment on the selection of different surgical types (free body enucleation or joint replacement) for KBD patients. Using propensity score method to perform a 1 ∶ 1 match on patients with different surgical types, and analyzing the influencing factors of KBD patients receiving different types of surgical treatment through multivariate logistic regression. Results:From 2018 to 2020, a total of 1 084 KBD patients in Shaanxi Province underwent surgical treatment, including 555 males (51.20%) and 529 females (48.80%), with a median age of 64 years old. There were 917 patients (84.59%) in the Guanzhong region (Tongchuan, Xi'an, Weinan, Xianyang, Baoji), 120 patients (11.07%) in the northern Shaanxi region (Yulin, Yan'an), and 47 patients (4.34%) in the southern Shaanxi region (Ankang, Hanzhong, Shangluo). The number of patients with KBD grade Ⅰ,Ⅱ, and Ⅲ was 401 (36.99%), 525 (48.43%), and 158 (14.58%), respectively. Five hundred and forty-eight patients (50.55%) underwent free body enucleation surgery, and 536 patients (49.45%) underwent joint replacement surgery. Univariate analysis showed that different genders, educational levels, living areas, disease severity, economic status, whether to relocate, type of drinking water, type of staple food, and source of staple food were the influencing factors for KBD patients to choose the type of surgery (χ 2 = 81.82, 22.38, 93.68, 22.38, 5.17, 15.68, 13.82, 39.37, 49.63, P < 0.05). Among 374 pairs of patients who underwent free body enucleation and joint replacement through propensity score matching, multivariate logistic regression analysis found that high school and above education level [odds ratio( OR) = 0.42, P = 0.008], Guanzhong region ( OR = 0.12, P < 0.001), relocation ( OR = 0.60, P = 0.004), and drinking well water ( OR = 2.15, P = 0.001) were the influencing factors for KBD patients to choose different surgical types for treatment. Conclusion:When performing surgical treatment for KBD patients in Shaanxi Province, clinicians can consider the severity of the disease, as well as factors such as the education level, living area, relocation status, and type of drinking water of KBD patients, to provide more suitable surgical types for KBD patients.

Objective:To systematically evaluate the effect of bariatric and metabolic surgery on bone metabolism in obese patients.Methods:Search terms for the present meta-analysis included "bariatric surgery, metabolic surgery, sleeve gastrectomy, gastric bypass, bone metabolic indicators, bone mineral density", both in English and corresponding Chinese. PubMed, WOS, Cochrane, CNKI, and VIP databases were searched for longitudinal studies from the establishment of the database to September 20, 2022. The data on bone mineral density and bone metabolic markers in obese patients before and after bariatric surgery were extracted. RevMan5.4 and Stata17.0 software were used for Meta-analysis.Results:A total of 8 clinical studies with 420 patients were included. The results of the meta-analysis showed that compared with the preoperative baseline, lumbar spine bone mineral density ( WMD=0.05, 95% CI: -0.00~0.1), femoral neck bone mineral density( WMD=0.10, 95% CI: 0.05-0.15), hip bone mineral density( WMD=0.14, 95% CI: 0.10-0.17), and serum vitamin D 3 ( WMD=-4.87, 95% CI: -6.34--3.40)were decreased, while parathyroid hormone ( WMD=10.04, 95% CI: 5.32-14.76) was elevated after surgery. Conclusions:Current evidence demonstrates that metabolic and bariatric surgery can lead to decreased bone mineral density and impairs in bone metabolic markers early after surgery. Roux-en-Y gastric bypass surgery cause more adverse effects on bone metabolism than sleeve gastrectomy. The results imply that all patients undergoing metabolic and bariatric surgery should be monitored for bone metabolism and routinely take vitamin D and calcium supplements.