ObjectiveTo evaluate the clinical efficacy and safety of Huaban Jiedu Formulation （化斑解毒方， HJF） in treating psoriasis vulgaris with blood-heat syndrome. MethodsA randomized， double-blind， placebo-controlled study was conducted with 60 patients diagnosed with psoriasis vulgaris of blood-heat syndrome. Patients were randomly assigned to either a treatment group or a control group， with 30 cases in each. The treatment group received HJF granules orally， one dose a day， combined with topical Qingshi Zhiyang Ointment （青石止痒软膏）， while the control group received placebo granules， one dose a day， combined with the same topical ointment. Both groups were topically treated twice daily of 28 days treatment cours. Psoriasis area and severity index （PASI）， visual analogue scale for pruritus （VAS）， traditional Chinese medicine （TCM） syndrome scores， dermatology life quality index （DLQI）， and psoriasis life stress inventory （PLSI） were assessed before treatment and on day 14 and day 28. Response rates for PASI 50 （≥50% reduction） and PASI 75 （≥75% reduction）， as well as overall clinical efficacy， were compared between groups. Serum levels of interleukin-6 （IL-6） and interleukin-17 （IL-17） were measured before and after 28 days of treatment. Adverse reactions during treatment were recorded. ResultsAfter 28 days of treatment， both groups showed significant reductions in PASI total score， lesion area score， erythema， scaling， and infiltration scores， pruritus VAS score， TCM syndrome score， DLQI， PLSI， and serum IL-6 and IL-17 levels （P＜0.05）. Compared to the control group， the treatment group had significantly greater improvements in PASI total score and erythema score， TCM syndrome score， serum IL-6 and IL-17 levels， and PASI 50 response rate after 28 days （P＜0.05）. Between-group comparisons of score differences before and after 28-day treatment revealed that the treatment group showed significantly better improvements in PASI total， lesion area score， erythema score， TCM syndrome score， DLQI， PLSI， and inflammatory markers （P＜0.05 or P＜0.01）. The total effective rate on day 14 and day 28 was 40.00% （12/30） and 83.33% （25/30） in the treatment group， versus 6.90% （2/29） and 41.38% （12/29） in the control group， respectively. The clinical efficacy in the treatment group was significantly superior to that in the control group （P＜0.05）. Mild gastric discomfort occurred in 3 patients in the treatment group and 1 in the control group. ConclusionHJF can effectively improve skin lesions and TCM symptoms relieve pruritus， enhance quality of life， and reduce inflammatory markers IL-6 and IL-17， in patients with blood-heat syndrome of psoriasis vulgaris， with a good safety profile.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

ObjectiveTo compare wild and cultivated Paeoniae Radix Rubra（PRR） in three aspects， including character， microscope， determination of primary and secondary metabolites. MethodSeventeen batches of wild and nine batches of cultivated PRR were collected，their character data were measured by vernier caliper and scales， and their paraffin sections were made by safranin-fixed green dyeing for the observation of microscopic features. The content of ethanol-soluble extracts and total tannin from wild and cultivated PRR was determined by the method of general principle 2201 and 2202 in the 2020 edition of Chinese Pharmacopoeia， the content of polysaccharides was determined by phenol-sulfuric acid method. Anthrone colorimetry was used to determine the content of starch， and Van Soest method of washing fiber was used to determine the content of fiber. The contents of fructose， glucose and sucrose in wild and cultivated PRR were determined by ultra-high performance liquid chromatography evaporative light scattering detection（UPLC-ELSD）， and the secondary metabolites（gallic acid， methyl gallate， catechin， oxypaeoniflorin， albiflorin， paeoniflorin， ellagic acid， 1，3，4，6-tetragalloylglucose， galloylpaeoniflorin， 1，2，3，4，6-O-pentagalloylglucose， naringenin， benzoylpaeoniflorin and benzoylalbiflorin） were determined by UPLC. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to analyze the data of wild and cultivated PRR， the contribution of different factors to the difference was determined according to the variable importance in the projection（VIP） value>1 and P<0.05. ResultIn term of characters， wild PRR showed the traditional characteristic of Zaopi Fencha， its outer skin was loose and easy to fall off， its surface had longitudinal furrow and wrinkle， but the outer skin of cultivated PRR was not easy to fall off， and its surface was relatively smooth. The radial texture of xylem of wild PRR cross-section was more obvious， showing radial striations， vacuoles and more cracks， while the radial texture of xylem of cultivated PRR cross-section was not obvious， dense and some had cracks. Microscopically， the number of radial vessels arranged in the xylem of wild PRR was more than that of cultivated PRR， the number of calcium oxalate clusters in the phloem and xylem of wild PRR was more than that of cultivated PRR， while the number of starch grains was significantly higher in cultivated PRR. In terms of the content of primary chemical constituents， the contents of polysaccharides and starch of cultivated PRR were significantly higher than those of wild PRR（P<0.05）， while the contents of cellulose， lignin， fructose and glucose of wild PRR were significantly higher than those of cultivated PRR（P<0.05）. The results of determination of 13 secondary metabolites showed that the contents of paeoniflorin， methyl gallate， catechin and oxypaeoniflorin in wild PRR were significantly higher than those in cultivated PRR（P<0.05）， while the contents of albiflorin， gallic acid， ellagic acid， naringenin， benzoylpaeoniflorin and benzoylalbiflorin were significantly lower than those of cultivated PRR（P<0.05）. A total of 10 variables contributing to the differentiation between wild and cultivated PRR were screened， including albiflorin， cellulose， benzoylpaeoniflorin， oxypaeoniflorin， naringenin， ellagic acid， starch， lignin， paeoniflorin and total tannins. ConclusionThere are significant differences between wild and cultivated PRR in characters， microscopic characteristics， contents of primary and secondary metabolites. It is suggested that the content ratio of paeoniflorin and albiflorin， the contents of oxypaeoniflorin and cellulose can be used as indicators to characterize production methods of PRR so as to improve the quality standard of PRR. This study can provide reference for the improvement of quality standard of PRR and the guidance of high quality production of PRR.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

Antiviral drug research and development is an important research direction in the current and future biomedical field. The research and development of antiviral drugs not only requires the application of new strategies and new technologies, but also requires the complementary advantages and close cooperation of project teams. Based on the latest progress in this field and the author's drug research practice, this paper summarizes the underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry.

Objective:To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection.Methods:A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data.Results:A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z ?=?-1.981, P ?=?0.048), aspartate aminotransferase (AST, z ?=?-3.956, P ?

This study was aimed at analyzing the changes in the cell proteome of HTR-8/Svneo human villous trophoblasts during infection with Listeria monocytogenes,to explore the mechanisms involved in L.monocytogenes infection of the placenta at the molecular level in host cells.Tandem Mass Tag(TMT)proteomics was used to compare the quantitative proteome be-tween the HTR-8/Svneo infection group and control group.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used to analyze enrichment in the molecular functions,biological processes,and metabolic pathways of differentially expressed proteins.A total of 76 285 peptides and 6 979 quantifiable proteins were identified.A total of 356 proteins showed significant differential expression:153 up-regulated and 203 down-regulated.The protein with the high-est fold change was microtubule motor protein(B4DYE2),and the protein with the lowest fold change was translation initia-tion factor 1(Q6IAV3).GO functional enrichment and KEGG metabolic pathway enrichment analyses indicated that the up-regulated proteins were involved primarily in biological processes and metabolic pathways such as the movement of microtubules and microfilament as well as autophagy,whereas the down-regulated proteins were involved mainly in primary metabolic pathways,such as carbon metabolism,nitrogen metabolism,amino acid biosynthesis,and nucleic acid metabolism,as well as ubiquitin mediated protein hydrolysis.In the process of infection of HTR-8/Svneo by L.monocytogenes,the basal metabolism of host cells may be significantly diminished,and the autophagy level may be high.The significant up-regulation of cell migration-inducing and hyaluronan-binding protein CEMIP(Q8WUJ3)suggested an important role of this protein in regulating the migration and invasion of trophoblast cells,thus causing adverse pregnancy outcomes.Our findings may provide new ideas for the study of the molecular mechanism of L.monocytogenes infection of the placenta.

Objective:To explore the long-term efficacy of laparoscopic fundoplication for proton pump inhibitor dependent gastroesophageal reflux disease (GERD).Method:Clinical data of proton pump inhibitor dependent GERD patients who underwent fundoplication at the Rocket Force Characteristic Medical Center from Jan to Jun 2012 were analyzed, including GERD symptom score, subjective symptom relief rate, PPI discontinuation rate and surgical satisfaction, as well as recurrence and complications.Result:A total of 160 GERD patients were included in this study, with 64% of patients having respiratory symptoms. Nissen and Toupet fundoplication were performed in 43 and 117 cases, respectively, with a follow-up time of (127±3) months. The postoperative GERD symptom scores of the patients were significantly lower than before treatment (all P<0.001); The subjective relief of overall symptoms in the digestive tract and airway problem was 90% (80%, 100%) and 100%, respectively. The PPI discontinuation rate was 86%, and the overall satisfaction rate of the treatment was 92%, and the satisfaction rate of patients with respiratory symptoms was 89%. 7% of patients experienced varying degrees of symptomatic recurrence, 4% of patients re-underwent endoscopic treatment and/or laparoscopic fundoplication due to symptom recurrence. The incidence of long-term postoperative dysphagia, bloating, belching, increased exhaust, abdominal pain, diarrhea, and constipation were 11.3%, 16.9%, 0, 1.3%, 0, 2.5%, and 5.6%, respectively. Conclusions:Laparoscopic fundoplication has good long-term efficacy in the treatment of GERD. A small number of patients may experience postoperative recurrence, as well as complications such as dysphagia and gas-bloat syndrome. Most recurrent patients can achieve good therapeutic effect by redoing endoscopic treatment or redoing surgery.