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.

Coronary microvascular dysfunction （CMD） is one of the important causes of myocardial ischemia and non-obstructive coronary artery ischemic symptoms. However， effective diagnostic methods and targeted treatment strategies for CMD are currently lacking. According to traditional Chinese medicine （TCM）， the comorbidity theory of "blood-vessel-cardiac collaterals" plays a central role throughout the entire development process of CMD. It suggests that in the clinical diagnosis and treatment of CMD， the treatment of blood， vessels， and cardiac collaterals should not be neglected. In light of this， insect medicines， known for their efficacy in promoting blood circulation， resolving stasis， and alleviating spasms， hold promise as a potential treatment for CMD. However， there is currently no research or summary on the use of insect medicines for the treatment of CMD. Therefore， this article took the comorbidity theory of "blood-vessel-cardiac collaterals" as the starting point and divided the pathogenesis of CMD into five evolution stages： Beginning in the blood （changes in blood components and hemorheology）， progressing in the vessels （atheromatous plaque formation and unstable plaques）， occurring in the cardiac collaterals （microvascular endothelial damage and microvascular constriction and spasms）， ending in the cardiac collaterals （microvascular remodeling）， and resulting in energy metabolism disorders throughout the process， so as to explore the pathogenesis and evolution of CMD. In addition， based on the modern pharmacological research on insect medicines， this article discussed the clinical application of insect medicines in the treatment of CMD from four aspects： Promoting blood circulation and removing blood stasis to relieve vessels' obstruction， relieving spasms to alleviate pain， combating poison with poison to disperse stagnation， and tonifying cardiac collaterals to nourish the heart， which aims to provide a theoretical basis for the use of TCM in treating CMD， broaden the scope of medication， and improve clinical efficacy.

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: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.

Heart failure refers to a group of clinical syndromes caused by structural or functional abnormalities of the heart that lead to impaired ejection or filling of the ventricles. The traditional Chinese medicine （TCM） theory of cardiac and renal coordination holds that the kidney governs water and plays a key role in maintaining the balance of fluid metabolism. Therefore， the treatment of water retention in heart failure can start from the heart and kidney. The basic pathogenesis of heart failure is kidney deficiency， blood stasis， and water stagnation， and the therapies including dredging the heart and kidneys， warming yang and excreting water， tonifying kidneys and activating blood， and dredging meridians and collaterals. Aquaporins （AQPs）， the key molecular basis of water metabolism， are involved in the pathogenesis of water retention in heart failure together with the arginine vasopressin system （AVP）， renin-angiotensin-aldosterone system （RAAS）， and diuretic resistance. Studies have shown that herbal medicines that regulate the heart and kidney can alleviate water retention in heart failure by targeting AQPs， thereby delaying or even reversing the progression of heart failure. This paper expounds the TCM name and pathogenesis of heart failure from the theory of cardiac and renal coordination， the role of AQPs in the pathogenesis of water retention in heart failure， and the modern connotation of the therapy of tonifying heart and kidney for heart failure， aiming to provide ideas for the prevention and treatment of water retention in heart failure by TCM.

Objective:To investigate whether the antibacterial copper sulfide (CuS)/graphene oxide (GO) nanosheets composite film can promote angiogenesis and osteogenesis in vitro. Methods:GO and CuS/GO nanosheets were synthesized and mixed into polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC) hydrogel films. The study was conducted in 4 groups: PVA/CMC/GO, PVA/CMC/CuS/GO, PVA/CMC (only PVA/CMC-based film) and blank control (no material). The PVA/CMC, PVA/CMC/GO and PVA/CMC/CuS/GO films were characterized by electron scanning microscopy and energy dispersive spectrometer. The biocompatibility of different films (PVA/CMC/CuS/GO films with concentrations of CuS/GO nanotablets of 0, 50, 100, 200, 400, and 800 μ g/mL) was evaluated by CCK-8, live/dead cell staining, and hemolysis test. The angiogenesis was evaluated by cell migration and tube forming test in vitro. Alkaline phosphatase and alizarin red staining were used to evaluate osteogenesis in vitro, and the expression of osteogenic genes was measured by immunofluorescence staining and RT-qPCR. In addition, the bacterial plate counting method and bacteriostatic circle method were used to evaluate the antibacterial activity of films. Results:In the PVA/CMC/GO and PVA/CMC/CuS/GO groups, the surface of the PVA/CMC-based film was smooth and flat whereas the nanosheets composite films were irregularly flaky and convex. The biosafety experiments showed that the PVA/CMC-based film composited with GO or CuS/GO nanosheets at the concentration of 100 μg/mL had good biocompatibility. The results of angiogenesis in vitro showed that the migration ratio of HUVEC cells in the PVA/CMC/CuS/GO group was significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In the experiment of tube forming area and length, the PVA/CMC/CuS/GO group was significantly better than the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The osteogenic differentiation in vitro displayed that the alkaline phosphatase and alizarin red staining of MC3T3-E1 cells in the PVA/CMC/CuS/GO group were significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In addition, the fluorescence intensity of immunofluorescence staining in alkaline phosphatase and type Ⅰcollagen on MC3T3-E1 cells, and the mRNA expression levels of osteogenic related genes including alkaline phosphatase, bone morphogenetic protein 2, osteocalcin and osteopontin in the PVA/CMC/CuS/GO group were significantly higher than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The antibacterial assay showed that the PVA/CMC/CuS/GO group had a significantly greater antibacterial activity and a significantly larger inhibition zone against Gram-positive bacteria and Gram-negative bacteria than the PVA/CMC/GO, PVA/CMC and control groups ( P< 0.001). Conclusions:PVA/CMC films composited with GO or CuS/GO nanosheets demonstrate ideal biocompatibility and antibacterial properties which promote angiogenesis and osteogenic differentiation in vitro. In particular, antibacterial PVA/CMC/CuS/GO composite films with the coupling function of angiogenesis and osteogenesis are expected to provide a new strategy for infectious bone defects.

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 compare the effect of age on clinical outcome of laparoscopic sleeve gastrectomy (LSG) in the obese patients.Methods:A total of 113 patients who underwent LSG due to obesity and metabolic disorders between 2013 and 2018 at Fudan University Pudong Hospital, and completed the scheduled follow-up (1, 3, 6, and 12 months after surgery) were included for the retrospective analysis. The patients were divided into three groups based upon pre-operative age, including 15 to 30 year-old group ( n=58), 31 to 45 year-old group ( n=32), and 45 to 65 year-old group ( n=23). The body weight related parameters, glycemic and metabolic related parameters, lipid panel as well as arterial blood pressure were compared at pre-operative baseline, 1, 3, 6, and 12 months after surgery. The quantitative data were analyzed by repeated measurement ANOVA, and the P value was corrected by Bonferroni method. And the categorical variables were analyzed by chi square test. Results:The preoperative baseline data showed that with the increase of age, the preoperative body mass index gradually decreased, which were (40.1±5.9) kg/m 2, (37.1±6.6) kg/m 2 and (35.3±7.4) kg/m 2 in 16 to 30, 31 to 45 and 46 to 65 year-old groups, respectively. Otherwise, other metabolic related parameters were comparable. At 12 months after LSG, there was no significant difference in the amount of weight loss among the groups, but the percentage of total weight loss (% TWL) and the percentage of total BMI loss (%TBMIL) decreased significantly with age increasing. The %TBMIL in 16 to 30, 31 to 45 and 46 to 65 year-old groups were 32.3±7.5%, 28.4±8.4% ( P<005 compared with 16 to 30 year-old group) and 25.7±8.2% (compared with 16 to 30 year-old group P<0.001), respectively. In the patients with preoperative HbA1c>7%, HbA1c reduction in the three groups at 12 months after operation were 3.20% (compared with 46-65 year-old group P<0.001), 2.64% (compared with 46-65 year-old group P<0.05) and 1.34%, respectively. The proportions of patients with HbA1c < 6.5% were 95.8%, 88.9% and 50.0%, respectively. LDL, triglyceride and arterial blood pressure in all groups decreased and HDL increased rapidly within 3 months after operation, but there was no significant difference among the three groups. Conclusions:The improvement of blood glucose metabolism and the remission rate of type 2 diabetes mellitus (T2DM) in the patients with older age were worse than those in the younger patients, and the T2DM in the younger patients tends to obtain better clinical remission after LSG; in terms of weight loss, with the increase of age, %TWL and %TBMIL also showed a decreasing trend; however, the improvement of blood lipid and blood pressure after LSG was not affected by the factor of age. This study implies that patients who meet the indications of metabolic and bariatric surgery should be suggested to receive surgical treatment early in order to achieve better clinical outcomes.

Objective:To investigate parents′ knowledge and attitude toward post-operative pain management in pediatric orthopedics and analyze influencing factors.Methods:A total of 170 parents of 6 to 16 years old children who underwent selective surgeries and were hospitalized because of limb fracture were conveniently selected in Children′s Hospital of Soochow University from April to December in 2019, They were investigated using the general data questionnaire, Pain Management Knowledge and Attitudes Questionnaire.Results:There were 167 parents completed questionnaires in our study. The mean score of parents′ knowledge, general attitude and negative attitude to pain medication were 15.0(3.00), 24.0(4.00) and 17.0(3.00) respectively. There were statistical differences between different educational levels of parents′ knowledge ( χ2 value was11.599, P=0.021), as well as different age of parent′s general attitude ( χ2 value was 7.053, P=0.029). Spearman-related results showed that parents′ cognition was positively correlated with general attitudes ( r value was 0.394, P<0.01). Conclusions:The majority of parents are at moderate to high level of knowledge, general attitude and negative attitude to pain medication. Pediatric nurses should pay more attention to parents′ knowledge deficit of and negative attitude toward pain assessment tools and pain-drugs to develop targeted educational intervention programs for promoting parental involvement.