Objective:To compare the efficacy and safety of omacycline with meropenem plus linezolid in the treatment of patients with pulmonary infection.Methods:The clinical data of 58 patients with pulmonary infection admitted to the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou Red Cross Hospital and Jiande First People’s Hospital from December 2021 to May 2022 were retrospectively analyzed. The patients were divided into the omacycline group ( n=29) and the meropenem combined with linezolid group (combined group, n=29). The omacycline group was given intravenous omacycline 200 mg or 100 mg, q. d, and the combined group was given intravenous meropenem (1 000 mg, t.i.d) and linezolid (600 mg, b. i.d). The clinical efficacy and drug-related adverse events of two groups were observed. SPSS 22.0 statistical software was used for data analysis. Results:In the omacycline group, 8 cases (27.6%, 8/29) were cured, 19 cases (65.5%, 19/29) were improved, and 2 cases (6.9%, 2/29) were worsened. In the combined group, 1 case (3.4%, 1/29) was cured, 26 cases (89.7%, 26/29) were improved, and 2 cases (6.9%, 2/29) died. There was a statistically significant difference between the two groups ( χ2=6.533, P=0.038). The respiratory failure occurred in 3 cases (10.3%, 3/29) of the omacycline group and 5 cases (17.2%, 5/29) of the combined group ( χ2=0.580, P=0.446). In those patients who were cured or improved, the median time from treatment initiation to disease remission was 3.0 (2.0, 5.5) d in the omacycline group and 5.0 (4.0, 6.0) d in the combined group ( Z=-2.122, P=0.034). There was no significant difference in the incidence of adverse reactions between the two groups [6.9% (2/29) vs. 13.8% (4/29), χ2=0.744, P=0.389]. Conclusion:Omacycline exhibits a good efficacy and safety in the treatment of patients with pulmonary infection, which may be prioritized for the treatment of pulmonary infections.

Objective:This work aims to investigate the virulence features, spore formation and the resistance mechanisms of major sequence types (STs) of clinical Clostridium difficile isolates from nosocomial infectious diarrhea. Methods:Clostridium difficile isolates were prospectively collected from 816 loose stool samples of in patients with antibiotic associated diarrhea at the Beijing Friendship Hospital of Capital Medical University from September 2017 to September 2019. The main ST types ST81 (26 strains), ST8 (15 strains) and ST42 (14 strains) of C. difficile were used as experimental strains. The polymerase chain reaction (PCR) and enzyme-linked immunoassay (ELISA) were performed to detect toxin genes and toxin production of different C. difficile ST types, respectively. The count of the colony forming units (CFU) of the strains as conducted by using the brain-heart infusion (BHI) agar plates. The antimicrobial resistance patterns of the strains to eleven kinds of antibiotics were determined by agar dilution method. The antimicrobial resistance genes: gyrA, gyrB and ermB were amplified and sequenced from the stains. Mutations in the resistance genes were analyzed by sequencing. Measure data was compared by Kruskal Wallis Test, differences in the resistance rates in three group were compared using Fisher exact test. Results:ST81 strains were identified as the tcdA-tcdB+/ cdtA-cdtB-toxin type, ST8 and ST42 strains belonged to tcdA+tcdB+/ cdtA-cdtB-toxin type. The toxin production of ST42 strains (41.9) were higher than ST8 (2.4) and ST81 groups (0.83) (all P<0.001). The number of spore quantities of ST81, ST8 and ST42 strains were 494×10 5CFU/ml, 160×10 5CFU/ml and 166×10 5CFU/ml, respectively. The spore quantities of ST81 strains were much higher than that of ST81 and ST42 strains (all P<0.001). From the in vitro susceptibility test, 100% (26/26) ST81 strains were featured as multi-drug resistant (MDR), and they were resistant to moxifloxacin, ceftriaxone, erythromycin and clindamycin. The resistance rates of ST8 strain to moxifloxacin, erythromycin and clindamycin were 9/15, 11/15 and 11/15, respectively. ST81 strains had higher resistance rates to moxifloxacin, clindamycin and erythromycin, compared to ST8 strains ( P=0.001, P=0.005 and P=0.005). All ST42 strains were susceptible to ceftriaxone and 3/14 ST42 strains were resistant to moxifloxacin. ST81 strains had higher resistance rates to ceftriaxone and moxifloxacin than the ST42 strains (both P<0.001). The positive rate of ermB in ST81 strains (100%, 26/26) were higher the ST8 strains (11/15) ( P<0.005). Amino acid mutation analysis showed that ST81and ST8 stains had one amino acid substitution in both GyrA and GyrB, but the amino acid substitutions were different in GyrB between two ST types. ST81 strains had two point-mutations: Thr82 replaced by Ile in GyrA, and Asp426 replaced by Val in GyrB. ST8 strains had point-mutation: Thr82 replaced by Ile in GyrA; Asp426 replaced by Asn in GyrB. For ST42 strains, Thr82 was replaced by Ile in GyrA. Conclusions:ST81 and ST42 strains were MDR. ST81 had higher spore ability, whereas ST42 strains had more virulence. ST81 strains and most of ST8 strains had high level of fluoroquinolones resistance. It is important to supervise persistently these three ST genotypes to prevent further dissemination.

Objective To evaluate the quality of the clinical trial literatures published on the treatment of COVID-19 with TCM, find out the shortcomings and put forward corresponding suggestions, in order to promote TCM against COVID-19. Methods "COVID-19", "New Coronavirus Pneumonia", "TCM", "Chinese Medicine", "Clinical Trial", "Lianhua Qingwen", "Huoxiang Zhengqi", "Jinhua Qinggan", and other keywords were used to search relevant literatures in CNKI and PubMed database. Among the all the screened relevant literatures on the treatment of COVID-19 with TCM, the literature quality was assessed according to evaluation criteria of clinical trial literatures. Results A total of 463 papers related to the treatment of COVID-19 with TCM were obtained. 440 papers on theoretical research on the network pharmacology mechanism of Chinese medicine treatment of COVID-19 were excluded. Among the 23 articles included in the quality analysis, there are 3 randomized controlled studies, 1 multi-center prospective randomized controlled trial, 2 disease case report trials, and 5 uncontrolled single arm studies, 5 controlled trials and 7 retrospective studies. In the period of more than half a year, although many clinical trial documents of TCM for the treatment of COVID-19 have been published, the clinical trial design reflected in most TCM clinical trials were not standardized. There are problems in "randomness and rationality", such as no control group, no randomization design, only case studies, no blinding method in controlling bias, and insufficient objectivity in the evaluation criteria of efficacy. All of these need to be improved. Conclusion The treatment of new coronavirus pneumonia with TCM still requires more and standardized clinical trial verifications and publications to generate strong evidence-based results, such as adding control groups, increasing sample size, and using blinding methods to increase the credibility of clinical trials.

Inflammatory bowel disease is a recurrent chronic intestinal inflammatory disease with unknown etiology and no effective treatment. Phosphodiesterase (PDE) regulates a variety of physiological and pathophysiological processes by mediating the hydrolysis of intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate. In recent years, a series of researches suggest that PDE inhibitors such as several PDE4 inhibitors, PDE5 inhibitors (sildenafil, tadalafil and vardenafil), PDE3 inhibitors (cilostazol), PDE9 inhibitor (PF-04447943) and PDE3/PDE4 double inhibitor (pumafentrine) have ameliorating effect on experimental colitis in animals. In clinical trials, PDE4 inhibitor apremilast showed more therapeutic advantage than tetomilast. This article reviews the recent research progress of PDE inhibitors in treatment of inflammatory bowel disease.
Animals ; Colitis ; Inflammatory Bowel Diseases/drug therapy* ; Phosphodiesterase 4 Inhibitors

Objective:To explore the feasibility of quantitative evaluation of extracellular volume (ECV) fraction in acute ST-segment elevation myocardial infarction (STEMI) by dual-layer spectral detector CT.Methods:The clinical and imaging data of 20 patients with STEMI who underwent cardiac contrast-enhanced CT and MRI from January to October 2019 in Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine were retrospectively analyzed.The dual spectral detector was used in the enhanced CT scan of the coronary artery with retrospectively gate and the late iodine enhancement with prospective gate. Conventional image and holographic spectral image were obtained by iterative and spectral reconstruction. The short axis image of the heart matched with MR image was obtained by multiplanar reconstruction. Based on the data of spectral based image, the IDD map was reconstructed for the calculation of myocardial CT-ECV during the late iodine enhancement. ECV of infarcted myocardium, salvageable myocardium and remote myocardium based on CT and MRI were calculated respectively. Bland-Altman consistency test and intra group correlation coefficient analysis (ICC) were used to compare the consistency of two measurements and different methods. The correlation between CT-ECV and MRI-ECV was compared by Spearman method.Results:The CT-ECV values of infarcted, salvageable, and remote myocardium were 51.21 (49.27, 53)%, 38.64 (36.17, 40)%, and 51.21 (49.27, 53)%, respectively. The difference was statistically significant ( H= 43.17, P<0.01). The CT-ECV value of infarcted myocardium was significantly higher than that of salvageable myocardium and remote myocardium ( Z=-24.60, 35.40, P<0.01), but there was no significant difference between salvageable myocardium and remote myocardium ( Z= 10.80, P=0.15). The T 1 values of infarcted myocardium, salvageable myocardium and remote myocardium were (1 554.85±70.94), (1 443.85±67.28) and (1 307.05±91.73) ms respectively, the difference was statistically significant ( F=51.35, P<0.01). The T 1 value of infarcted myocardium was higher than that of salvageable myocardium and remote myocardium ( t=-5.07, 9.55, P<0.01), and salvageable myocardium was significantly higher than that of remote myocardium ( t=5.38, P<0.01). The MRI-ECV values of infarcted myocardium, salvageable myocardium and remote myocardium were 55.00 (49.27, 57.75)%, 33.50 (29.00, 35.00)%,and 27.00 (26.00, 29.00)%, respectively. The difference was statistically significant ( Z= 47.12, P<0.01). MRI-ECV of infarcted myocardium was significantly higher than that of salvageable myocardium and remote myocardium ( Z=37.45, -20.30, P< 0.01), and salvageable myocardium was significantly higher than that of remote myocardium ( Z = 17.15, P<0.05). The difference between CT-ECV and MRI-ECV measured by two physicians was good. The bias of Bland-Altman analysis was -0.1% (95% CI:-5.5%-5.2%), 0.8% (95% CI:-9.8%-8.2%), and the ICC values were 0.92 and 0.94, respectively. The bias of Bland-Altman analysis in CT-ECV and MRI-ECV consistency test was 4.00% (95% CI:-9.0%-16.9%) and ICC value was 0.88, which had a good correlation ( r=0.75, P=0.001). Conclusions:The iodine density based ECV fromdual-layer spectral detector CT can be used to quantitatively evaluate the changes of extracellular space after acute STEMI, which is helpful to quantitatively evaluate the histological changes after myocardial ischemia.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective To investigate the characteristic changes of biochemical markers of mineral metabolism, vascular calcification, and renal osteodystrophy in an adenine-induced rat model of chronic kidney disease (CKD). Methods A total of 20 male Sprague Dawley rats (SD rats) were randomly divided into two groups: the normal group fed with a diet without adenine, and the CKD group fed with an adenine-containing diet (7. 5 g/kg) for the first 4 weeks and then a diet without adenine for the following 2 weeks. At the end of the 2nd week, serum biochemical markers were detected. At the end of the 6th week, the SD rats were sacrificed and serum biochemical markers were detected once again. The aortas were collected for pathological examination and detection of vascular calcium and phosphorus contents. Femurs and the fifth lumbar vertebrae were taken for bone mineral density (BMD) measurement and bone histomorphometric analysis. Results At the end of the 2nd and 6th weeks, compared with the normal control group, the levels of serum creatinine, urea nitrogen, phosphorus and parathyroid hormone (PTH) in the CKD group were significantly increased (P＜0. 05 or P＜ 0. 01), and the level of serum calcium was significantly decreased (P＜ 0. 05 or P＜ 0. 01). Medial layer vascular calcification of the aorta occurred in 50％ of the rats in the CKD group, but was not observed in the normal control group. Vascular calcium and phosphorus contents were significantly higher in the CKD group compared with the normal control group (P＜ 0. 05). The BMD of total femur, cortical and trabecular bone tissues of the femur, and the fifth lumbar vertebra was significantly decreased in the CKD group (P＜ 0. 05 or P＜ 0. 01). The histomorphometric analysis showed that both bone resorption and bone formation of the trabecular bone in the CKD group were increased, indicating a high bone turnover status. The volumes of both trabecular and cortical bones of rats in the CKD group were significantly lower than that of the normal control group (P ＜ 0. 05 or P ＜ 0. 01). However, the trabecular bone mineralization was not significantly different between the two groups. Conclusions The adenine-induced rat model of chronic kidney disease (CKD) established in this study shows reduced serum calcium and increased serum phosphorus and PTH, and medial layer vascular calcification of the aorta. With respect to renal osteodystrophy, this model shows a high trabecular bone turnover, normal trabecular bone mineralization, and low bone volume of cortical and trabecular bone, which meets the characteristics of osteitis fibrosa. This model may become a useful tool for future study of chronic kidney disease-mineral and bone disorder (CKD-MBD).

Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD. Methods: This was a prospective case-control study. From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University. Twenty-two healthy children were enrolled in the control group. Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years. The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected. Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology. The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software. The intestinal flora characteristics between the two groups were compared with t test or Mann-Whitney U test and Willcoxon W test. Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m², t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046). The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036). At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10^-3 vs. 63.212 (46.133, 172.071) ×10^-3, Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10^-3 vs. 0.000 (0.000, 0.031) ×10^-3, Z=-2.729, P=0.006) . At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10^-3 vs. 356.821 (161.049, 403.037) ×10^-3, Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10^-3 vs. 54.721 (31.911, 146.410) ×10^-3, Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10^-3 vs. 0.432 (0.029, 2.257) ×10^-3, Z=-2.112, P=0.035). Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism. Besides, these three function genes were related to Bacteroides, Prevotella, Bifidobacterium and Ruminococcus. Conclusion NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.

Objective:To study the difference in anti-hepatic fiborsis components between pre-and post-processed Trionyx Sinensis Carapace to guide the clinical application of Trionyx Sinensis Carapace. Methods:SDS-PAGE gel electrophoresis was used to compare the constituents in pre-and post-processed Trionyx Sinensis Carapace, and the inhibitory effect on the proliferation of HSC-T6 was deter-mined by MTT. Results:The processed Trionyx Sinensis Carapace had much more components than the crude Trionyx Sinensis Cara-pace,and the relative molecular mass in the first-level band decreased resulting in the generation of micromolecular polypeptides. Both pre-and post-processed Trionyx Sinensis Carapace had anti-hepatic fibrosis, while the vinegar-processed Trionyx Sinensis was more ef-fective. Conclusion:The difference in the active components in pre- and post-processed Trionyx Sinensis Carapace is obvious, which provides foundation for the clinical application and further researches.

Objective To investigate the effect of electroacupuncture at different points on auditory brainstem response (ABR) in a rat model of sodium salicylate-induced tinnitus.Method Forty-one male Wistar rats were randomly allocated to saline control (saline), sodium salicylate model (SA), electroacupuncture at Tinggong+ Yifeng (EA), electroacupuncture at Waiguan+ Zhongzhu (AA) and electroacupuncture at Zusanli+ Sanyinjiao (LA) groups. The saline group consisted of five rats and each of the other groups, nine rats. The model was made by intraperitoneal injection of sodium salicylate 275 mg/kg. The saline control group was injected with a corresponding volume of saline. Various acupoint electroacupuncture groups were given electroacupuncture at bilateral Tinggong+ Yifeng, Waiguan+ Zhongzhu and Zusanli+ Sanyinjiao, respectively, at 30 min after model making. Electroacupuncture lasted 30 min. The ABRs were recorded before model making and once every one hour for five consecutive hours after model making. The stimulus sounds were short clicks and tone bursts of frequencies of 4, 8, 16 and 32 kHz. The ABR threshold was used as an assessment index.Results Under the condition of clicks, there was a statistically significant difference in the ABR threshold at one to five hours after model making between the SA, EA, AA or LA group and the saline group (P<0.05), at two to five hours after model making between the EA or AA group and the SA group (P<0.05) and at one hour after model making between the LA and SA groups (P<0.05). Under the conditions of 4, 8 and 16 kHz, there was a statistically significant difference in the ABR threshold at one to five hours after model making between the SA, EA, AA or LA group and the saline group (P<0.05). Under the condition of 32 kHz, there was a statistically significant difference in the ABR threshold at one to five hours after model making between the SA, AA or LA group and the saline group (P<0.05). Under the condition of 4 kHz, there was a statistically significant difference in the ABR threshold at two to five hours after model making between the EA and SA groups (P<0.05) and at four to five hours after model making between the AA and SA groups (P<0.05). Under the condition of 8 kHz, there was a statistically significant difference in the ABR threshold at two to five hours after model making between the EA or AA group and the SA group (P<0.05). Under the condition of 16 kHz, there was a statistically significant difference in the ABR threshold at two, four and five hours after model making between the EA and SA groups (P<0.05). Under the condition of 32 kHz, there was a statistically significant difference in the ABR threshold at one to five hours after model making between the EA and SA groups (P<0.05).Conclusion Electroacupuncture at both periauricular and forelimb points can improve the ABR threshold in sodium salicylate-treated rats. The effect of electroacupuncture at periauricular points is superior to that at forelimb points.