Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.

OBJECTIVE: To explore the relationship between the estrogen-like effect of seeds of Cuscuta chinensis and the fingerprints of the seeds of Cuscuta chinensis from different habitats, thus to provide a basis for the establishment of Chinese medicine quality standards based on the relationship between the fingerprinting and pharmacodynamics. METHODS: The fingerprints of seeds of Cuscuta chinensis samples from different habitats were established by HPLC, and the active ingredients of seeds of Cuscuta chinensis with estrogenlike effect were screened by uterotrophic method and MTT assay, and the spectrum-activity relationship was analyzed by bivariate correlation analysis. RESULTS: Twenty-six peaks of seeds of Cuscuta chinensis Lam. were identified as common peaks by HPLC. It was shown by uterotrophic and MTT assay that the seeds of Cuscuta chinensis from No. 20 habitat could significantly promote the proliferation of MCF-7 cells and the increase of uterus weight compared with the blank control group and the positive control group. It was shown that the estrogenic effect of seeds of Cuscuta chinensis was the combined effect of a variety of chemical constituents. CONCLUSION: There exsists correlation between the fingerprints of the seeds of Cuscuta chinensis from different habitats and their estrogenic activity.

New drug research and development is a technology-intensive industry with high investment, high cycle and high risk. In recent years, with the rapid development of modern disciplines such as omics technology, bioinformatics, high-throughput and high-content screening, and artificial intelligence, the research and development of small-molecule drugs has presented a new paradigm characterized by "integrated medicinal chemistry". This review summarizes new enabling drug discovery technologies, the emergence of new subfields formed through integration innovations and practical chemistry toolbox in the field of medicinal chemistry.

Background The advantages of endothelium keratoplasty(EK)include without corneal surface incision and sutures,remaining normal corneal topography,minimizing astigmatism and providing a healthy donor endothelial cell count and function.Using anterior segment optical coherence tomography(AS-OCT) to examine the morphology of the corneal graft after EK is helpful for the evaluation of the outcome of EK.ObjectiveThis study applies AS-OCT to observe the relationship of recipient cornea and donor graft and offer a basis for the evaluation of operative outcome.MethodsThe clinical data from 44 eyes of 42 patient who received DSAEK in Peking University Eye Center from September 2007 through April 2009 was reviewed retrospectively.These patients included 30 male and 12 female with the age from 15 to 83 years.Structure of cornea and relationship between recipient cornea and graft disc after surgery were clinically examined and recorded by slit-lamp digital camera and AS-OCT.This study was approved by the Ethics Committee of Peking University.Written informed consent was obtained from all of the patients before the operation.ResultsThe donor graft attached to posterior central surface of recipient in 28 eyes under the slit-lamp microscopy and AS-OCT.The thickness of donor graft was decreased,and graft sticked more closely to recipient cornea and was more transparent with the lapse of time.Complete dislocation of the donor graft in early stage was found in 5 eyes(11.36%) and partial dislocation in 2 eyes(4.55%).Curliness of graft edge occurred in 1 eye(2.27%) and eccentricity of donor graft in 8 eyes(18.18%).ConclusionAS-OCT can display the morphology and structure of cornea as well as the relationship between donor graft and recipient after DSAEK.It is helpful for evaluating the clinical effectiveness of DSAEK.

Objective: To observe the changes in numbers and degranulation status of local mast cells (MCs) of the complementary acupionts, as well as the concentrations of serum histamine and bradykinin after acupuncture at rat's complementary acupionts of Yanglingquan (GB 34) and Yinlingquan (SP 10), for exploring the mechanisms of the synergistic effect of complementary acupionts. Methods: Using random number table method, 40 Wistar rats were randomly divided into a blank control group (group K), an acupuncture at Yanglingquan (GB 34) group (group A), an acupuncture at Yinlingquan (SP 9) group (group B), an acupuncture at Yanglingquan (GB 34) and Yinlingquan (SP 9) group (group AB), and an acupuncture at points near Yanglingquan (GB 34) and Yinlingquan (SP 9) group (group CD), 8 rats in each group. Group A received acupuncture at Yanglingquan (GB 34); group B received acupuncture at Yinlingquan (SP 9); group AB received acupuncture at Yanglingquan (GB 34) and Yinlingquan (SP 9); group CD received acupuncture at the control points [points 3 mm away from Yanglingquan (GB 34) and Yinlingquan (SP 9) respectively]. Acupuncture was performed at bilateral points in each group. Rats in group K were fixed using the same method as rats in the other 4 groups without acupuncture stimulation. Needles of 0.35 mm in diameter and 40 mm in length were used for acupuncture. Needle handle was connected to the G6805-Ⅱ mode electroacupuncture (EA) device after needling qi was obtained, with sparse-dense wave, frequency of 2 Hz/100 Hz and current of 1 mA to keep the needle handles slightly tremulous while the rats kept quiet. Rats were continuously stimulated by EA for 20 min each time. Experimental interventions were conducted on the 1st, 3rd, 5th and 7th days when the experiment started, for 4 times in total. Specimens from rats in each group were collected 2 h after the 7th day. The levels of histamine and bradykinin in serum were detected by enzyme-linked immunosorbent assay (ELISA). Local tissues of the points were used to prepare cryosections. The changes of MCs were observed after toluidine blue staining. Results: Compared with group K, the numbers and degranulation rates of MCs in group A, group B, group AB and group CD were significantly increased (all P<0.05). The number and degranulation rate of MCs in group AB were significantly higher than those in group A, group B and group CD (all P<0.05). The order of histamine levels from high to low was: group AB >group B > group A > group CD > group K, and the differences were statistically significant (all P<0.05); the levels of bradykinin in group AB, group A and group B were significantly higher than those in group K and group CD (all P<0.05). There was no significant difference in the bradykinin level between group A and group B, nor between group CD and group K (all P>0.05). Conclusion: The number and degranulation rate of MCs of the complementary acupionts are significantly increased after acupuncture at complementary acupionts of Yanglingquan (GB 34) and Yinlingquan (SP 9) of rats, and the serum levels of histamine and bradykinin are increased, which may be one of the mechanisms of the synergism produced by the combination of complementary acupionts.

Objective To investigate the effects of ropivacaine infiltration combined with dezocine on the agitation during recovery from general anesthesia in the patients undergoing cerebral surgery.Methods Sixty patients of both sexes,aged 18-64 yr,of ASA physical status Ⅰ or Ⅱ,undergoing elective neurosurgery under general anesthesia,were randomly divided into 4 groups (n =15 each) using a random number table:control group (group C),ropivacaine group (group R),dezocine group (group D),and ropivacaine + dezocine group (group RD).Group C received local infiltration with normal saline 20 ml at 10 min before skin incision,and normal saline 2 ml was injected intravenously at 30 min before the end of operation.The patients received local infiltration with 0.5％ ropivacaine 20 ml at 10 min before skin incision,and normal saline 2 ml was injected intravenously at 30 min before the end of operation in group R.Group D received local infiltration with normal saline 20 ml at 10 min before skin incision,and dezocine 10 mg was injected intravenously at 30 min before the end of operation.The patients received local infiltration with 0.5％ ropivacaine 20 ml at 10 min before skin incision,and dezocine 10 mg was injected intravenously at 30 min before the end of operation in group RD.The time for recovery from anesthesia,extubation time,and development of agitation after extubation in PACU were recorded.Agitation was assessed and scored.Ramsay sedation score and VAS score were recorded immediately after extubation.The development of cardiovascular events and respiratory depression was recorded within 10 min after extubation.Before induction of anesthesia (T0),at the end of surgery (T1) and immediately after extubation (T2),blood samples were collected from the dorsal artery of foot for deter mination of the levels of blood glucose,plasma cortisone,epinephrine and norepinephrine.Results Compared with group C,the agitation score,incidence of agitation,VAS score,and incidence of postoperative hypertension were significantly decreased in R,D and RD groups,especially in R and D groups.The time for recovery from anesthesia and time for extubation were significantly shorter in R and RD groups than in group C.Ramsay sedation scores were significantly higher at the onset of extubation in R,D and RD groups than in group C.Ramsay sedation scores were significantly higher in D and RD groups than in group R.Compared with group C,the levels of blood glucose,plasma cortisone,epinephrine and norepinephrine were significantly decreased in R,D and RD groups,especially in group RD.Conclusion Ropivacaine infiltration combined with dezocine can reduce the agitation during recovery from general anesthesia in the patients undergoing cerebral surgery.

Objective To explore the personality change in patients with epilepsy during the interictal period and the correlation between clinical features and personality change. Methods One hundred and fifteen patients with idiopathic or cryptogenic epilepsy were chosen as the epileptic group and 42 age- and sex-matched healthy subjects served as controls. All participants were evaluated by Mini Mental Status Examination and Brief Psychiatric Rating Scale to ensure the normality of cognition and mental state.Personality was evaluated by adult version of Eysenck Personality Questionnaire (EPQ)in interictal epilepsy patients and healthy controls.Scores of psychoticism (P),extraversion (E),neuroticism (N) and lie (L)were obtained using computer software. Pearson correlation analysis and logistic regression were used to investigate the scores of EPQ and influential factors.Results P and N scores were significantly elevated in epilepsy patients compared with controls ( P scores:50.48 ± 9.55 vs 46.59 ± 7.28,N scores:51.13 ±12.89 vs 46.83 ± 9.40 ; t =2.374,2.266,both P ＜ 0.05 ),while E scores were significantly decreased (51.74 ± 10.74 vs 60.37 ± 9.84;t =- 4.511,P ＜ 0.01 ).There were no significant differences in L scores.Multivariate analysis showed that disease duration was independently correlated to P scores (β =0.043,P＜0.05),while education was correlated to E scores (β =0.109,P ＜ 0.05 ).There were no significant correlations between personality scores,patient age,gender,age of onset,frequency,seizure type,National Hospital Seizure Severity Scale scores,family history,history of status epilepticus and antiepileptic drugs usage.Conclusions High psychoticism and neuroticism and low cxtraversion scores are correlated to patients with epilepsy during the interictal period.Disease duration is an independent risk factor for psychoticism personality,and education level is an independent risk factor for extraversion personality in epilepsy patients.

Objective To investigate the clinical efficacy of coronary renal shunt via splenic vein for portal hypertension (PHT) after splenectomy.Methods The retrospective descriptive study was adopted.The clinical data of 5 patients with PHT who were admitted to the People's Hospital of Ningxia Autonomous Region from August 2012 to April 2015 were collected.Operative procedures:two procedures of coronary renal shunt via splenic vein (SV) were carried out after primary splenectomy.Procedure 1:the SV was freed from the residual end to the right for 5-6 cm in length and end-to-side spleno-renal shunt was carried out.The anterior wall of superior mesenteric vein (SMV) was exposed beneath the pancreatic neck and dissected behind the neck upward until the upper edge of the SV and its confluence with the left gastric vein (LGV) were exposed.The SV was ligated with clip between portal vein (PV) and LGV to let blood flow from LGV drain through the whole course of SV to left renal vein (LRV).Procedure 2:the peritoneum at the inferior border of the pancreas was incised,and the junctions of the SV and SMV and junctions of the SV and LGV were exposed.The inferior mesenteric vein (IMV) was divided between ligations.Dissection of the SV was carried out to the left for 3-4 cm in length and was divided.Its distal end was tied and proximal stump anastomosed to LRV by the end-to-side anastomosis.The SV was ligated with clip between PV and LGV.The right gastric and gastroepiploic vessels were ligated at the junction of the antrum and the body,and from this point,the hepatogastric ligment and the omentum were divided upward and downward respectively to completely separate the venous flow between the hepatointestinal area and the stomach in the two procedures.Patients took oral enteric-coated aspirin and warfarin after operation.(1) Intraoperative observation indicators included surgical procedures,operation time,volume of blood loos and free portal pressure (FPP).(2) Postoperative observation indicators included recovery of patients,time to anal exsufflation,time for diet intake,time of abdominal drainage,duration of hospital stay and occurrence of complications.(3)The follow-up using telephone interview and outpatient examination was performed to detect the changes of platelet (PLT),portal vein thrombosis (PVT),patency of spleno-renal vein anastomosis,oral anticoagulants and gastroesophageal varices up to October 2015.Measurement data with skewed distribution were analyzed by M (range).Results (1)Intraoperative observation indicators:5 patients underwent successful coronary renal shunt via splenic vein.Two patients received procedure 1 and 3 patients received procedure 2.Operation time and volume of blood loss were 226 minutes (range,195-298 minutes) and 425ml (range,235-820 mL).FPP was 3.46 kPa (range,2.69-4.61 kPa) before spleen resection,2.69 kPa (range,2.11-3.07 kPa) after spleen resection,2.98 kPa (range,2.30-3.36 kPa) after spleno-renal anastomosis,respectively.(2) Postoperative observation indicators:5 patients had good recovery,and time to anal exsufflation,time for fluid diet intake,time of abdominal drainage removal and duration of hospital stay were respectively 3 days (range,2-4 days),3 days (range,2-4 days),5 days (range,4-9 days) and 14 days (range,10-17 days).Of 5 patients,1 was complicated with pleural effusion and atelectasis and 1 with serum tumescence of incision.(3) Follow-up situations:5 patients were followed up for a median time of 18 months (range,6-36 months).The level of postoperative PLT was continuously growing,and the dose of oral warfarin was increased according to the level of growing PLT.The follow-up results of procedure 1 in 2 patients:1 patient was followed up for 36 months and complicated with splenic vein thrombosis at postoperative month 6,and underwent transcatheter hepatic arterial chemoembolization (TACE) due to primary liver cancer at postoperative month 12,and then no special treatment was conducted due to splenic vein occlusion and sever esophageal varices without red-color sign or bleeding at postoperative month 36.The other patient was followed up for 24 months,and didn't undergo special treatment due to mild hepatic encephalopathy with a level of blood ammonia of 76 μmol/L at postoperative month 3,and then was found to have mild esophageal varices at postoperative month 18 by computed tomography (CT) and gastroscopy.Three patients using procedure 2 were followed up at month 6,12,18,with increased body mass index (BMI) and without occurrence of peritoneal effusion and hepatic encephalopathy,and they were complicated with mild gastroesophageal varices by reexamination of CT angiography and gastroscopy at postoperative month 6.Conclusion Coronary renal shunt via splenic vein for PHT after splenectomy could relieve hypersplenism and reduce selectively vein decompression of gastroesophageal varices.

Objective:To compare the difference of epileptiform discharges detection in patients with epilepsy between the 25 electrodes electroencephalogram (EEG) system proposed by the International Federation of Clinical Neurophysiology in 2017 and the previous 19 electrodes EEG system.Methods:Patients suspected of epilepsy or with confirmed epilepsy who need a follow-up EEG were collected in Zhongshan Hospital, Fudan University from March 2018 to November 2019, and conventional video-EEG recording was performed on all patients for two hours with the standard 25 electrodes EEG system. Two neurophysiologists reviewed the recordings blindly using the 19 electrodes system and the 25 electrodes system, marking the epileptiform discharges and their amplitudes. Finally, the data were statistically analyzed.Results:A total of 403 patients were included in the study, in which 263 cases were diagnosed as epilepsy, including 129 cases of generalized epilepsy, 115 cases of temporal lobe epilepsy, 13 cases of frontal lobe epilepsy, two cases of parietal lobe epilepsy and four cases of occipital lobe epilepsy. In 115 temporal lobe epilepsy patients, 76 (66.09%) and 100 (86.96%) records were detected epileptiform discharges by the 19 or 25 electrodes EEG system respectively, and the difference was statistically significant (χ2=13.939, P<0.001). While in patients with non-temporal lobe epilepsy, there was not statistically significant difference between the two systems. In 76 patients whose temporal epileptiform discharges were detected by the two systems, the amplitudes of epileptiform discharges in the newly-added inferior temporal electrodes (F9/F10, T9/T10, P9/P10) and the original temporal electrodes (F7/F8, T7/T8, P7/P8) were (61.53±22.64) μV and (48.25±20.90) μV, respectively, with statistically significant difference between the two groups ( t=5.486, P<0.001). In patients with abnormal [79.59% (39/49) vs 61.22% (30/49), χ2=3.967, P=0.046] and normal [95.45% (42/44) vs 70.45% (31/44), χ2=9.724, P=0.003] imaging, the ability of the 25 electrodes EEG system to detect epileptiform discharges was higher than that of the 19 electrodes EEG system. Conclusion:The 25 electrodes EEG system can significantly improve the detection ability of temporal epileptiform discharges in patients with epilepsy, which is recommended for regular use to increase the detection ability of temporal area abnormal wave and assist the diagnosis and treatment of epilepsy.

Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.