OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus （T2DM） insulin resistance （IR） rats. METHODS Sixty male SD rats were randomly divided into control group （12 rats） and modeling group （48 rats）. The modeling group was fed with a high- fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model. The model rats were randomly divided into model group， the compatibility of Astragali Radix-Puerariae Lobatae Radix group [QG group， 4.05 g/（kg·d）， intragastric administration]， ferroptosis inhibitor ferrostatin-1 group [Fer-1 group， 5 mg/kg by intraperitoneal injection， once every other day]， the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group [QG+erastin group， 4.05 g/（kg·d） by intragastric administration+erastin 10 mg/（kg·d）， intraperitoneal injection]. After 4 weeks of intervention， serum fasting blood glucose （FBG） and fasting insulin （FINS） were measured in each group of rats， and homeostasis model assessment of insulin resistance （HOMA-IR） and the natural logarithm of insulin action index（IAI） were calculated； the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate transaminase （AST） and alanine transaminase （ALT）， Fe2+ and Fe content， glutathione （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） levels， NADP+/NADPH ratio and reactive oxygen species （ROS） were determined. The pathological morphology of its liver tissue was observed； the protein expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， long-chain acyl-CoA synthetase 3 （ACSL3）， ACSL4， ferritin mitochondrial （FTMT）， and cystine/glutamate anti-porter （xCT） in the liver tissue of rats were detected. RESULTS Compared with control group， the liver cells in the model group of rats showed disordered arrangement， swelling， deepened nuclear staining， and more infiltration of inflammatory cells， as well as a large number of hepatocyte vacuoles and steatosis； FBG （after medication）， the levels of TC， TG， LDL-C， AST， ALT， FINS， MDA and ROS， HOMA-IR， Fe2+ and Fe content， NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated， while the levels of HDL-C， GSH and SOD， IAI， protein expressions of GPX4， FTH1， ACSL3， FTMT and xCT were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators， the differences in the changes of most indicators were statistically significant （P＜0.01 or P＜0.05）. Compared with QG group， the improvement of the above indexes of QG+erastin group had been reversed significantly （P＜0.01）. CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats， and alleviate IR degree， ion overload and pathological damage of liver tissue. The above effects are related to the inhibition of ferroptosis.

OBJECTIVE To explore the therapeutic effect and safety of Maiwei Yangfei Decoction(MWYF)in the treatment of idiopathic pulmonary fibrosis of qi-yin deficiency type.METHODS A total of 58 patients with idiopathic pulmonary fibrosis of qi-yin deficiency type were randomly divided into an experimental group and a control group with 29 cases in each group according to a 1:1 ratio.Two cases dropped out of the experimental group and three cases dropped out of the control group.The control group received standardized treatment of Western medicine,and the experimental group received MWYF on the basis of the treatment of the control group.The treatment course of both groups was 3 months.The TCM syndrome score,lung function,6-minute walking distance(6MWD),transcutaneous blood oxygen saturation(SpO2),high-resolution computed tomography(HRCT)score,St.George's respir-atory questionnaire(SGRQ)score and serum sialoglycoprotein antigen(KL-6)level of the two groups were compared before and after treatment.Blood routine and liver and kidney function of the two groups were detected before and after treatment,and the occurrence of adverse reactions during treatment was recorded.RESULTS After treatment,the total score of TCM syndrome of the two groups was significantly improved(P<0.01),and the experimental group was better than the control group(P<0.01);the DLCO%of the experi-mental group increased(P<0.05),and the experimental group was higher than the control group(P<0.05).The experimental group showed significant improvement in 6MWD,HRCT grid shadow,SGRQ symptom score and total score,and serum KL-6 level(P<0.05,P<0.01),which was better than the control group(P<0.05,P<0.01).No serious adverse events occurred in either group dur-ing the treatment.CONCLUSION MWYF combined with standardized Western medicine treatment can effectively improve the clini-cal symptoms of patients with idiopathic pulmonary fibrosis of qi-yin deficiency type,reduce the expression level of serum KL-6,and has a definite effect and good safety.

Objective:To determine the content of the released nickel ion through the 7 extraction media to extract the Ni-Ti wires and to plot the curve of the released nickel ion so as to identify a leaching medium that can be substituted for blood for in vitro Ni release evaluation. Methods:The release of Ni through microwave digestion/inductively coupled plasma mass spectrometry (ICP-MS) in the goat serum was determined. Because of the high content of Ni release, it could be determined by diluting the extraction medium, and other extraction media could be determined directly. Ni release standard curves were plotted by the release amount and different time point variables. Though the different extraction media Ni release curves confirm the specificity of extraction media instead of blood.Results:By analyzing the Ni release curves of seven leaching media, it was found that none of these seven extraction media was suitable for the evaluation of Ni release in in vitro leaching media. Considering the safety of the leaching medium and the simplicity of preparation, hydrochloric acid solution was chosen as the leaching medium, but the concentration needed to be diluted accordingly. Finally, a hydrochloric acid solution was created as an alternative to blood for the in vitro study of Ni release from Ni-Ti alloy cardiovascular products, with a volume fraction of 0.005%. Conclusions:The in vitro leaching medium that can replace blood was found to be hydrochloric acid for the time being, but its concentration was too high, resulting in too much Ni release as well, which deviated from the actual situation. Therefore, the hydrochloric acid solution was diluted step by step, and the Ni release curve was examined until it was close to the clinical release level, and the actual concentration was determined, thus laying a solid foundation for the subsequent evaluation of the safety and risk.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

Objective Taking three-dimensional (3D) motion capture system (MoCap) as the gold standard, a deep learning fusion model based on bi-lateral long short-term memory (BiLSTM) recurrent neural network and linear regression algorithm was developed to reduce system error of the Kinect sensor in lower limb kinematics measurement. Methods Ten healthy male college students were recruited for gait analysis. The 3D coordinates of the reflective markers and the lower limb joint centers were simultaneously collected using the MoCap system and the Kinect V2 sensor, respectively. The joint angles of lower limbs were calculated using the Cleveland clinic kinematic model and the Kinect kinematic model, respectively. The dataset was constructed using the MoCap system as the target and the angles via the Kinect system as the input. A BiLSTM network and a linear regression model for all lower limb angles were developed to obtain the refined angles. A leave-one subject-out cross-validation method was employed to study the performance of the models. The coefficient of multiple correlations (CMC) and root mean square error (RMSE) were used to investigate the similarity and the mean deviation between the joint angle waveforms via the MoCap and the Kinect system. ResultsIn comparison with the linear regression algorithm, the BiLSTM had better performance in the aspect of dealing highly nonlinear regression problems, especially for hip flexion/extension, hip adduction/abduction, and ankle dorsi/plantar flexion angles. The deep learning refined model significantly reduced the system error of Kinect. The mean RMSEs for all joint angles were mainly smaller than 10°, and the RMSEs of the hip joint were smaller than 5°. The joint angle waveforms presented very good similarity with the golden standard. The CMCs of joint angles were greater than 0.7 except for hip rotation angle. Conclusions The markerless gait analysis system based on deep learning fusion model developed in this study can accurately assess lower limb kinematics, joint mobility, walking functions, and has good prospect to be applied in clinical and home rehabilitation.

Objective:We aimed to observe the effects of loganin(Log)on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase(AMPK)signaling in obese mice.Methods:A high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research(ICR)mice.Body weight was measured weekly and fasting blood glucose(FBG)was determined every 2 weeks.Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed.The serum levels of total cholesterol(TC),triglyceride,high-density lipoprotein-cholesterol,low-density lipoprotein-cholesterol(LDL-C),and free fatty acids(FFA)were measured.The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting,and gut microbiota were characterized using 16S rDNA sequencing.Results:Log significantly decreased the body weight and the FBG in obese mice(P＜.05),and it could restore FBG to normal levels.The total cholesterol,LDL-C,and FFA levels were significantly reduced by Log compared with the obese controls(TC:P=.0020;LDL-C:P=.0233;FFA:P=.0127),and the glucose tolerance of animals was significantly improved(P=.0477).The western blot results showed that Log could upregulate the protein expression of Adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPKα),Sirtuin 1(SIRT1),and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1α)in skeletal muscle tissue of obese mice.16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice.Conclusions:Log was effective in reducing body weight and improving glucolipid metabolism in obese mice,probably through activating AMPK signaling and regulating intestinal microbial diversity.

In this report, a series of novel piperidine-substituted thiophene[3,2-]pyrimidine derivatives were designed to explore the hydrophobic channel of the non-nucleoside reverse transcriptase inhibitors binding pocket (NNIBP) by incorporating an aromatic moiety to the left wing of the lead . The newly synthesized compounds were evaluated for anti-HIV potency in MT-4 cells and inhibitory activity to HIV-1 reverse transcriptase (RT). Most of the synthesized compounds exhibited broad-spectrum activity toward wild-type and a wide range of HIV-1 strains carrying single non-nucleoside reverse transcriptase inhibitors (NNRTI)-resistant mutations. Especially, compound exhibited the most potent activity against wild-type and a panel of single mutations (L100I, K103N, Y181C, Y188L and E138K) with an EC ranging from 6.02 to 23.9 nmol/L, which were comparable to those of etravirine (ETR). Moreover, the RT inhibition activity, preliminary structure-activity relationship and molecular docking were also investigated. Furthermore, exhibited favorable pharmacokinetics (PK) profiles and with a bioavailability of 33.8%. Taken together, the results could provide valuable insights for further optimization and compound holds great promise as a potential drug candidate for the treatment of HIV-1 infection.

Objective To evaluate the application value of low-dose CT (LDCT) in physical examination for coal miners with different exposure time.Methods The consecutive three-year imaging data of 972 coal miners with over 20-year exposure were retrospectively reviewed.All miners were divided into 3 groups according to different exposure time,including 317 cases with less than 10 years,299 cases with 10-20 years and 356 cases with more than 20 years.All subjects underwent LDCT examination every year during three consecutive years.Results Baseline LDCT:As the exposure time was prolonged (with less than 10 years,10-20 years and more than 20 years),the number of coal miners has increased with non-calcified pulmonary nodules,interstitial pulmonary lesions,clinically cured or stable stage of pulmonary tuberculosis,pulmonary calcification and pulmonary fibrous stripes,but without statistically significant difference.The detection rates of lung bullae,aorta and coronary artery sclerosis were also increased mildly,with the prolonged exposure time.There was no significant correlation between exposure time and detection rates of bronchiectasis,pulmonary inflammatory lesions,lymph node enlargement or calcification,pleural lesions.The exposure time of 6 cases of malignant nodules and 2 cases of active tuberculosis was more than 10 years.During a two-year follow-up using LDCT scan,there were no significant changes in most of intrapulmonary,pleural and mediastinal lesions.Neither were in pulmonary nodules less than or equal to 4 mm.Three pulmonary nodules with 4-8 mm diameters were enlarged.Most of the inflammatory lesions have changed in size.Conclusion The LDCT scan has a certain value for chest physical examination of the coal miners with different exposure time.It is very necessary to screen the high-risk population of coal miners with exposure time of more than 10 years using LDCT.LDCT reexamination has significant value for pulmonary nodules and inflammatory lesions with diameter of more than 4 mm.Most of intrapulmonary,pleural and mediastinal lesions have no obvious change in the short term,and make an annual reexamination unnecessary,neither does a negative baseline LDCT.

OBJECTIVE: To strengthen the occupational protection of pharmacy intravenous admixture service (PIVAS) staff, and to ensure the safe and timely delivery of drugs. METHODS: The cytotoxic drug packing bag was made by oxford cloth, velvet cotton, pearl cotton, silica gel, activated carbon, rope, etc. Taking Paclitaxel liposomes for injection as an example, the application effect of packing bags was observed. A total of 156 medical orders of PIVAS formulated Paclitaxel liposomes for injection were selected and divided into test group and control group aoccording to random number table. The dispensing drugs were packed with cytotoxic drug packing bag in trial group, and packed with previous plastic packing bag in control group. The packing time of each drug, the delivery time, leaking and shattering, the breakage processing time and loss amount were compared between 2 groups. RESULTS: There was no statistical significance in the delivery time between 2 groups (P＞0. 05). The packing time of trial group was significantly longer than control group; there were 16 bottles of leaking in the control group, and 8 bottles of shattering; In trial group, 3 bottles were leaking but not spilled over (infiltrated in the silica gel layer), and there was no shattering bottle; the breakage processing time of trial group was significantly shorter than that of control group; the loss amount was significantly less than that of control group, with statistical significance (P＜0. 05). CONCLUSIONS: The cytotoxic drug packaging bag developed in this study can play a spill-proof, anti-seismic role, reduce the loss of valuable drugs, and also strengthen the occupational safety and health protection of medical staff.