Based on the theory of traditional Chinese medicine （TCM） chronomedicine， this paper explores the pathogenesis and treatment strategies of colorectal cancer mediated by circadian rhythm disorders. It is believed that the imbalance of yin and yang is isomorphic to the disorder of biological clock genes， which is the root cause of the disease. The disharmony of ying and wei （营卫） corresponds to the imbalance of immunity and metabolism， which is the pivot of the disease. The disorder of qi movement is related to the imbalance of intestinal barrier， which is the manifestation of the disease. Accordingly， relevant strategies are proposed， including chronochemotherapy regimen that aligns with biological rhythms to enhance efficacy and reduce toxicity， acupuncture based on the ebb and flow of midnight and midday which selects acupoints along meridians to harmonize qi and blood， and a timed medication strategy that matches the disease mechanism by administering drugs at optimal times. These strategies aim to deepen the understanding of the pathogenesis of colorectal cancer mediated by circadian rhythm disorders from the perspective of TCM chronomedicine， thereby providing new ideas for clinical practice.

Oxidative stress is an important pathophysiological pathway for the development and progression of ferroptosis. Under pathological conditions, the production of a large amount of reactive oxygen species （ROS） exceeds the buffering capacity of the antioxidant defense system, resulting in lipid peroxidation and cell ferroptosis in the state of oxidative stress. Cellular lipid peroxidation can generate toxic aldehydes, which interact with important biological macromolecules and break the normal function of cells. At present, it has been found that aldehyde dehydrogenase 2 （ALDH2） can eliminate these aldehydes and regulate the cycle of toxic aldehydes-ROS-oxidative stress-lipid peroxidation, thereby improving the prognosis of diseases associated with iron death. Ferroptosis and ALDH2 were introduced, and the current researches on ALDH2 were summarized to improve diseases associated with iron death, which can open up new directions for the subsequent research on the treatment of diseases associated with iron death.

Approximately 25% of renal cell carcinoma (RCC) patients are already at an advanced stage at the time of initial diagnosis. Additionally, nearly 30% of patients with localized RCC eventually develop distant metastases even after undergoing radical surgery. Traditional chemotherapy and radiotherapy have shown limited effect on advanced RCC treatment, resulting in poor prognosis, with a 5-year survival rate of only about 8%. In recent years, immunotherapy for RCC has become a significant focus of research. With further research, the treatment options for advanced RCC have become increasingly diverse. The exploration of the current clinical applications and research advancements in immunotherapy for advanced RCC could offer medical evidence for optimizing treatment strategies for advanced RCC patients.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

In order to evaluate the consistency of the release behavior between the self-made saxagliptin and metformin hydrochloride sustained-release tablets and the reference preparations in vitro, the similarity of the dissolution curves between the self-made preparations and the reference preparations in four dissolution mediums: HCl (pH 1.0), acetate buffer saline (pH 4.5), phosphate buffer saline (pH 6.8) and pure water, and the gel morphology and strength of the self-made preparations and the reference preparations in the HCl (pH 1.0) solution medium were compared.Results showed that in four dissolution mediums, the dissolution rates of saxagliptin in the self-made preparations and the reference preparations at 15 min were greater than 85%, and the ?2 similarity factors of metformin hydrochloride were 89, 83, 80, 86, all greater than 50, so the dissolution of the self-made preparations was consistent with those of the reference preparations.The volume expansion rate, water absorption rate and erosion rate were consistent with those of the reference preparations, and the gel strength of the self-made preparations was the same as that of the reference preparations.The in vitro release behaviors of the self-made preparations and the reference preparations are consistent, which provide a good guarantee for bioequivalence.

The ulnar collateral ligament (UCL) of the elbow is the primary stabilizer to resist valgus stress. Its injury is common in overhead throwing athletes, mainly caused by repeated valgus forces, and can cause elbow pain and affect the career of athletes. A common treatment of ulnar collateral ligament injury for overhead throwing athletes is ulnar collateral ligament reconstruction (UCLR). At present, the UCLR techniques have been constantly improved, mainly in graft structure, incision exposure, management of the ulnar nerve, and methods of humeral and ulnar fixation. This paper is to review the anatomy and biomechanics of UCL, as well as techniques, key points, postoperative complications and rehabilitation of UCLR so as to deepen the understanding of UCLR in clinicians.

Objective To investigate the effect of warfarin on coagulation and hemorheology in patients with atrial fibrillation.Methods 106 cases of admitted in our hospital from October 2014 to October 2016 were randomly divided into observation group(53 cases)and control group(53 cases).The control group re-ceived routine treatment,the observation group received routine and warfarin treatment.The two groups were treated for 4 weeks.The therapeutic effects were compared between the two groups.Before and after treat-ment,indicators of heart function,blood coagulation and hemorheology were observed.Results The total effi-ciency of observation group(92.45%)was higher than that of the control group(73.58%,P<0.05).After treatment,the TT and APTT of the two groups both increased(P<0.05);The TT and APTT of the observa-tion group were higher than that of the control group(P<0.05);The plasma viscosity,erythrocyte aggrega-tion index,and fibrinogen of the two groups decreased(P<0.05);The plasma viscosity,erythrocyte aggrega-tion index,fibrinogen of the observation group were lower than that of the control group(P<0.05).Conclu-sion Warfarin has obvious curative effect on patients with atrial fibrillation,and can improve the function of blood coagulation and hemorheology.

Objective To solve the problems of clinical laboratory module in mobile medical unit such as miscellaneous and mixed equipment,disordered packages,and weak mobility and responsiveness.Methods The concept of modularization was used for the secondary optimization of clinical laboratory equipment and consumables.The specialized vehicle for clinical laboratory was designed with considerations on the advantages of clinical laboratory shelter in equipment and medical vehicle in mobility,so as the values of clinical laboratory module were enhanced in mobile medical unit.Results Modular and standardized management of clinical laboratory equipment was realized to solve the existing problems of equipment.Conclusion The equipment supportability and mobility are enhanced in mobile medical unit,so that the requirements can be fulfilled for medical support missions at peace time and wartime.

Objective To evaluate the cost-utility of different hepatitis E vaccination strategies in women aged 15 to 49.Methods The Markov-decision tree model was constructed to evaluate the cost-utility of three hepatitis E virus vaccination strategies.Parameters of the models were estimated on the basis of published studies and experience of experts.Both methods on sensitivity and threshold analysis were used to evaluate the uncertainties of the model.Results Compared with non-vaccination group,strategy on post-screening vaccination with rate as 100％,could save 0.10 quality-adjusted life years per capital in the women from the societal perspectives.After implementation of screening program and with the vaccination rate reaching 100％,the incremental cost utility ratio (ICUR) of vaccination appeared as 5 651.89 and 6 385.33 YuaWQALY,respectively.Vaccination post to the implementation of a screening program,the result showed better benefit than the vaccination rate of 100％.Results from the sensitivity analysis showed that both the cost of hepatitis E vaccine and the inoculation compliance rate presented significant effects.If the cost were lower than 191.56 Yuan (RMB) or the inoculation compliance rate lower than 0.23,the vaccination rate of 100％ strategy was better than the post-screening vaccination strategy,otherwise the post-screening vaccination strategy appeared the optimal strategy.Conclusion Post-screening vaccination for women aged 15 to 49 from social perspectives seemed the optimal one but it had to depend on the change of vaccine cost and the rate of inoculation compliance.

Background Laser peripheral iridoplasty (LPI) is widely used in the treatment of glaucoma by flattening the iris and widening angle of anterior chamber (AA).However,no evidence suggests the optimal site of LPI in iris.Objective This study was to compare the therapeutic effects of LPI at different sites of iris for glaucoma.Methods Glaucoma models were established in the right eyes of 40 healthy adult male pigment rabbits by intrachamber injection of 0.1 ml compound carbomer solution with 0.3％ carbomer and 0.025％ dexamethasone.The models were randomly divided into model control group,corneoscleral limbus group,one spot from corneoscleral limbus group and two spots from corneoscleral limbus group.LPI was performed at corresponding site of iris by 532 nm argon laser with the spot diameter 500 μm,energy 300 mW,exposure time 0.3 seconds and laser number 24 spots,and the rabbits in the model control group did not receive LPI.Intraocular pressure (IOP),coefficient of outflow facility (C value) were measured and calculated with Schi(o)tz tonometer before LPI and 2,4,7,14 and 30 days after LPI,and anterior chamber depth (ACD),AA,anterior chamber angle opening distance within 500 μm radius from scleral spur (AOD500) were measured with ultrasound biomicroscope (UBM).The eyeballs were extracted 30 days after LPI,and the chamber angle were observed under the optical microscope after hematoxylin and eosin staining.The use and care of the animals complied with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.Results UBM showed that compared with the model control group,the anterior chamber angle was evidently widened in all the LPI groups,with the best effectiveness in the one spot from corneoscleral limbus group and the worst one in the two spots from corneoscleral limbus group.Compared with the model control group,the IOP was evidently reduced,and C values,AA and AOD500 were significantly increased in the corneoscleral limbus group,one spot from corneoscleral limbus group and two spots from corneoscleral limbus group after LPI,showing significant differences among the four groups (IOP:Fgroup =16.848,P ＜ 0.01;C value:Fgroup =9.629,P ＜ 0.01;AA:Fgroup =62.336,P＜0.01;AOD500:Fgroup =77.779,P ＜ 0.01).IOP was reduced and C value,AA and AOD500 were increased in 2,4,7,14 and 30 days after LPI as compared with before LPI,with significant differences over time (IOP:Ftime =3.041,P =0.011;C value:Ftime =4.311,P＜0.01;AA:Ftime =14.627,P＜0.01;AOD500:Ftime =20.378,P＜0.01).Compared with the model control group,the ACD was significantly increased in the corneoscleral limbus group and one spot from corneoscleral limbus group,and that in the two spots from corneoscleral limbus group was significantly reduced,and the ACD was insignificantly increased over time after LPI (Fgroup =18.017,P＜0.01;Ftime =0.022,P =1.000).Hematoxylin and eosin staining showed that the trabecular meshwork and adhesion of tissure were reopened and the anterior chamber angle was widened after LPI.Conclusions LPI can widen anterior chamber angle and lower the IOP.The best therapeutic outcome for glaucoma is displayed when LPI is performed at the iris site corresponding to one spot from the corneoscleral limbus.