In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Objective To investigate the efficacy of Fuzheng Hejie Prescription(composed of Scutellariae Radix,Lonicerae Japonicae Flos,Agastachis Herba,Bupleuri Radix,Atractylodis Rhizoma,Glycyrrhizae Radix et Rhizoma,etc.)in the treatment of respiratory viral infections in children and to observe its effect on inflammatory factors and immune function.Methods A total of 203 children with respiratory viral infection of H1N1 virus were randomly divided into 101 cases in the observation group and 102 cases in the control group.Both groups were given the routine treatment for subsiding fever,maintaining water-electrolyte balance,and ensuring enough sleep.And additionally,the control group was given Ribavirin Granules and Ibuprofen Granules,and the observation group was given Fuzheng Hejie Prescription based on the treatment for the control group.The course of treatment covered 7 days.The changes of traditional Chinese medicine(TCM)syndrome scores and the levels of immunological indicators and inflammatory factors in the two groups were observed before and after the treatment.Moreover,the clinical efficacy,symptom resolution time and the incidence of adverse reactions were compared between the two groups of children.Results(1)In the course of the trial,one case fell off in the observation group and 2 cases fell off in the control group,and eventually 100 children in each group were included in the trial.(2)After 7 days of treatment,the total effective rate of the observation group was 93.00%(93/100),and that of the control group was 88.00%(88/100),and the intergroup comparison showed that the therapeutic effect of the observation group was superior to that of the control group,but the difference was not statistically significant(χ2= 1.454,P = 0.228).(3)After treatment,the scores of primary symptoms and secondary symptoms as well as the total TCM syndrome scores in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the time for the resolution of clinical symptoms such as fever,cough,expectoration and sore throat in the observation group was significantly shorter than that in the control group(P＜0.01).(5)After treatment,the levels of immunological indicators of T lymphocyte subset CD3+ and CD4+ in the two groups were increased compared with those before treatment(P＜0.05),and the levels of CD8+ and B cells were decreased compared with those before treatment(P＜0.05).The intergroup comparison showed that the increase in the levels of CD3+ and CD4+ as well as the decrease in the levels of CD8+ and B cells of the observation group was significantly superior to that of the control group(P＜0.01).(6)After treatment,the levels of inflammatory factors of serum amyloid A(SAA),C-reactive protein(CRP),serum tumor necrosis factor alpha(TNF-α),soluble interleukin 2 receptor(SIL-2R),and interleukin 6(IL-6)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels of interleukin 2(IL-2)and interferon γ(IFN-γ)ls were all significantly increased compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum SAA,CRP,TNF-α,SIL-2R,and IL-6 levels and the increase of serum IL-2 and IFN-γ levels in the observation group were significantly superior to those in the control group(P＜0.01).(7)The incidence of adverse reactions in the observation group was 2.00%(2/100),which was significantly lower than that of 8.00%(8/100)in the control group,but the difference was not statistically significant(χ2 = 3.789,P = 0.052).Conclusion Fuzheng Hejie Prescription exerts certain effect in treating children with respiratory viral infection of H1N1 virus,which can effectively decrease children's TCM syndrome scores,regulate the inflammatory response,improve the immune function,accelerate the relief of clinical symptoms and shorten the course of the disease.

The electrophysiological activity of the gastrointestinal tract and the mechanical anti-reflux structure of the gastroesophageal junction are the basis of the anti-reflux function of the stomach. Proximal gastrectomy destroys the mechanical structure and normal electrophysiological channels of the anti-reflux. Therefore, the residual gastric function is disordered. Moreover, gastroesophageal reflux is one of the most serious complications. The emergence of various types of anti-reflux surgery through the mechanism of reconstructing mechanical anti-reflux barrier and establishing buffer zone, and the preservation of, the pacing area and vagus nerve of the stomach, the continuity of the jejunal bowel, the original gastroenteric electrophysiological activity of the gastrointestinal tract, and the physiological function of the pyloric sphincter, are all important measures for gastric conservative operations. There are many types of reconstructive approaches after proximal gastrectomy. The design based on the anti-reflux mechanism and the functional reconstruction of mechanical barrier, and the protection of gastrointestinal electrophysiological activities are important considerations for the selected of reconstructive approaches after proximal gastrectomy. In clinical practice, we should consider the principle of individualization and the safety of radical resection of tumor to select a rational reconstructive approaches after proximal gastrectomy.
Humans ; Stomach Neoplasms/surgery* ; Gastrectomy ; Gastroesophageal Reflux ; Esophagogastric Junction/surgery* ; Pylorus/pathology*

Objective:To investigate the current status of early nutritional support treatment in patients with severe acute pancreatitis complicated with intestinal fistula,and analyze the impact on the clinical outcomes of patients.Methods:Retrospective analysis was used to select the relevant data of 60 ICU admission patients with severe acute pancreatitis complicated with intestinal fistula of a tertiary hospital in Nanjing from May 2022 to May 2023,the statistics analysis of the patients'early nutritional support treatment were carried out,and explored the impact on clinical outcomes of patients.Results:A total of 45(75％)and 57(95％)patients started EN and PN treatment within 48 h of admission.The EEN calorie compliance rate after admission of 1 week was 44.2％.There was a difference in mechanical ventilation time and hospitalization expenses between the early enteral nutrition calorie group and non-compliance group,but no significant difference in the length of ICU stay(P＞0.005).Conclusion:The early enteral nutrition compliance rate of patients with severe acute pancreatitis combined with intestinal fistula is slightly lower.Compared with the early enteral nutrition non-compliance group,the enteral nutrition standard group has shorter mechanical ventilation time and lower total hospitalization costs,which can improve the clinical outcome of patients.

Animals ; Rats ; Diabetes Mellitus ; Vascular Endothelial Growth Factor A

OBJECTIVE: To explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. METHODS: A cross-sectional stratified study was performed to select 108 patients with GradeⅡKOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m^-2 with an average of (23.80±2.86) kg·m^-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m^-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m^-2 with an average of(23.42±2.97) kg·m^-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m^-2 with an average of (24.15±2.33) kg·m^-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m^-2 with an average of (23.79±2.49) kg·m^-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. RESULTS: There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). CONCLUSION The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.
Aged ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Medicine, Chinese Traditional ; Osteoarthritis, Knee ; Syndrome ; Wind ; Cold Temperature

OBJECTIVE: To investigate the application of 3D printing percutaneous surgical guide plate in closed reduction and cannulated screw internal fixation of femoral neck fracture. METHODS: The clinical data of 12 patients with femoral neck fracture from March 2019 to March 2022 were retrospectively analyzed. Patients were divided into observation group and control group according to different operation plans, with 6 cases in each group. The observation group received percutaneous operation guide plate assisted closed reduction and hollow screw internal fixation, while the control group received closed reduction and hollow compression screw internal fixation. The operation time, intraoperative blood loss, fluoroscopy times, and Kirschner needle puncture times were compared between two groups. The location of screws were recordedon postoperative X-ray films, follow-up time, time of complete fracture healing, Harris score of hip joint and the incidence of complications were recorded on postoperative X-ray films. RESULTS: The operation time of observation group (32.17±6.18) min was shorter than that of control group (53.83±7.31) min (P<0.05). The amount of intraoperative bleeding in the observation group (18.33±2.94) ml was less than that in the control group (38.17±5.56) ml(P<0.05). The times of fluoroscopy in the observation group (7.50±1.05) were less than those in the control group (21.00±4.82) (P<0.05). The number of Kirschner needle punctures (8.00±0.63) in observation group was less than that in control group (32.67±3.08) (P<0.05). The follow-up time was(12.88±0.74) months in observation group and (12.83±0.72) months in control group, there was no significant difference between two groups (P>0.05). One year after operation, Harris score of hip joint in the observation group was(82.00±4.52) points, while that in the control group was(81.00±3.41) points, there was no significant difference between two groups(P>0.05). The time of complete fracture healing in the observation group was (7.50±1.05) months, while that in the control group was (7.67±1.21) months, there was no significant difference between two groups(P>0.05). The parallelism of the screws in the observation group was (0.50±0.11) ° and (0.76±0.15) °, which were lower than that in the control group (1.57±0.31) ° and (1.87±0.21) ° (P<0.05). The screw distribution area ratio (0.13±0.02) cm2 in the observation group was higher than that in the control group (0.08±0.01) cm2 (P<0.05). No complications such as necrosis of femoral head, nonunion of fracture, shortening of femoral neck and withdrawal of internal fixation occurred in both groups. CONCLUSION The application of 3D printing percutaneous surgical guide plate improves the accuracy and safety of closed reduction and cannulated screw internal fixation for femoral neck fracture. It has the advantages of minimally invasive, reducing radiation exposure, fast and accurate, shortening the operation time and reducing intraoperative bleeding.
Humans ; Retrospective Studies ; Treatment Outcome ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal ; Bone Screws ; Printing, Three-Dimensional

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage

Objective: To evaluate the effect of ultrasound diagnosis of thyroid micro-malignant nodules and accumulate practical experience for the management of active surveillance for them, so as to avoid overtreatment. Methods: A total of 949 patients who were diagnosed with thyroid malignant nodules using ultrasonography, with the nodules being less than 1 cm in size and without regional lymph node metastasis or distant metastasis, were included. They were treated by the same surgeon of the Department of Head and Neck Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from February 2014 to December 2020. 112 patients chose immediate surgery. The rest patients were asked to accept ultrasound examination every 6 months to 1 year. Follow-up endpoints: tumor size growth of 3 mm, tumor volume increase greater than 50%, lymph node metastasis or distant metastasis. Results: The median follow-up time was 19 months. 713 patients underwent surveillance for more than 6 months. Of the 713 patients, 570 (79.9%) were women, with mean age at 43.5 years old. Tumor progression was observed in 47 (6.6%) patients with a cumulative incidence of 2.7% (1 year), 7.2% (2 years) and 9.5% (3 years). In multivariate analysis, patient age [HR=0.508, 95%CI: 0.275-0.939, P=0.031], lesion number [HR=2.945, 95%CI: 1.593-5.444, P=0.001] and tumor size [HR=2.245, 95%CI: 1.202-4.192, P=0.011] at the beginning of observation were independent risk factors for tumor progression in patients with minimal thyroid malignant nodules during follow-up. During a median (range) active surveillance of 19 (6-80) months, 74 patients chose surgery during the surveillance. Among the 186 patients who underwent surgery, only 3 patients were diagnosed with fibrotic nodules in pathology, while the rest were papillary thyroid carcinoma. The ultrasound accuracy reached 98.4%(183/186). Conclusions: Ultrasonography is an effective method of diagnosing malignant thyroid nodules. Thyroid micro-malignant nodules progress slowly. As a result, it is safe to observe them instead of taking immediate surgery. Patient age, lesion number and tumor size at the beginning of observation are independent risk factors for the tumor progression of malignant nodules.
Humans ; Female ; Adult ; Male ; Thyroid Nodule/surgery* ; Carcinoma, Papillary/surgery* ; Lymphatic Metastasis ; Thyroid Neoplasms/surgery* ; Thyroidectomy/methods* ; Watchful Waiting ; Ultrasonography ; Retrospective Studies

IMM0306 is a recombinant human signal regulatory protein α-anti-CD20 mouse chimeric antibody fusion protein, intended to treat refractory or recurrent CD20 positive B-cell non-Hodgkin lymphoma (B-NHL) in clinical. In this study, an ELISA method was established to evaluate the pharmacokinetics of IMM0306 in human serum. The experiment was approved by the Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences (No. CTR20192612). Recombinant human CD47 protein was coated with the plate overnight, blocking the plate with 5% skin milk for 2 h. After washing, 100 μL per well standard and unknown samples were added, and incubated for 1.5 h. After washing, the detection antibody Anti-IMM0306-Biotin was added and incubated for 1 h, and then HRP-labeled streptavidin was added for 1 h, and the color was detected. The optimal concentration of coating reagent was 2 μg·mL^-1 by ELISA method, and the optimal dilution of anti-IMM0306-biotin and SA-HRP were 1∶500 and 1∶5 000, respectively. The lower limit of quantitation was 4 ng·mL^-1, and the standard curve range was 4-100 ng·mL^-1. The verification results of the method meets the corresponding acceptance criteria, and can be used in IMM0306 clinical pharmacokinetic studies.