Chronic fatigue syndrome (CFS) is a common problem in military maritime navigation, which greatly affects the safety of military missions. The use of animal models to carry out research on the mechanism of CFS and treatment measures is a common method. This paper systematically introduced the construction methods of CFS models such as single-factor and multi-factor models, summarized common evaluation indicators of CFS, including behavioral and biochemical indicators, and summed up key characteristics of CFS animal models in military oceanic navigation combined with common causes of CFS in military contexts, such as prolonged continuous work, high-intensity physical activity, sleep deprivation, psychological stress, and extreme environmental conditions. The key characteristics of the animal models included, but not limited to, chronic fatigue, sleep disorders, impaired cognitive function, psychological stress responses, and abnormal biochemical indicators. Furthermore, this article identified future research directions for CFS animal models in military oceanic navigation to enhance the application value of the models and provide robust support for the health protection and disease prevention of military personnel.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

Objective To analyze the clinical characteristics and regularity of aristolochic acid nephropathy (AAN) induced by drugs containing aristolochic acid. Methods The clinical data of 111 patients with AAN induced by aristolochic acid were reviewed. The clinical features, medication and treatment of AAN were analyzed. Results Among 111 patients, there were more females than males (2.58∶1), 101 cases (90.99%) were over 50 years old； the mean age was (63.70±11.67) years old;the average duration of medication was (8.08±6.94) years. The drugs involved were Guanxinsuhe pill and Longdanxiegan pill in 106 cases (95.50%). Serum creatinine increased in 108 cases, urea nitrogen increased in 106 cases and hemoglobin decreased in 103 cases, most of which were hypogravity urine, mild to moderate proteinuria and occult blood. Ultrasonic examination revealed that the kidneys were damaged to varying degrees. Pathological biopsy of kidney showed renal tubular damage. Most patients had an insidious onset and varying degrees of progression, which were not proportional to the age and the duration of taking the medicine. In clinical, the renal function was progressively damaged, most of which were irreversible and with a poor prognosis. Conclusion Patients with renal impairment differed greatly individually, and the renal damage was not paralleled with the medication duration and dose of drugs containing aristolochic acid.AAN progressed rapidly, and the disease still progressed even after stopping taking drugs containing aristolochic acid. Strengthening pharmacovigilance, implementing early diagnosis and effective intervention could help to reduce the occurrence of AAN and attenuate its development.

Objective To investigate the changes of blood lipid and glycosylated hemoglobin (HbA1c) levels in obese type 2 diabetes (T2DM) patients and their relationship with insulin resistance (Homa-IR). Methods A total of 120 cases of T2DM newly diagnosed in Motuo County, Tibet from February to October 2022 were selected as the observation group. According to BMI, the patients were divided into diabetes normal weight group (46 cases), overweight group (43 cases) and obesity group (31 cases); 145 healthy subjects were selected as the control group. The levels of HbA1c, fasting blood glucose (FPG), fasting insulin (FINS), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) were detected in the study subjects, and Homa-IR and Homa-β indices were calculated. The height, weight, and abdominal circumference were measured. The differences in the levels of the above indicators between the observation group patients and the control group, as well as among various subgroups within the observation group were compared. The influencing factors of Homa-IR in obese T2DM patients were analyzed. Results Compared with the control group, a significant increase in BMI, abdominal circumference, blood pressure, HbA1c, FBG, FINS, TC, TG, LDL-C, UA, visceral fat area, and the levels of Home-IR and Home-β was found in the observation group (all P<0.05). There were significant differences in BMI, abdominal circumference, and the levels of FINS, Homa IR, Homa-β, and HbA1c in diabetes patients with different BMI (all P<0.05). Correlation analysis showed that TG levels in obese T2DM patients in the observation group were significantly correlated with HbA1c (r=0.396, P=0.027), Homa-IR (r=0.405, P=0.024), and Home-β (r=-0.401, P=0.025); LDL-C was significantly correlated with Homa-IR (r=0.411, P=0.022) and Homa-β (r=-0.412, P=0.021); HbA1c was significantly positively correlated with BMI (r=0.371, P=0.040). Conclusion Insulin resistance is closely related to TG, LDL-C, and BMI in obese T2DM patients from the Motuo ethnic minority of Tibet, suggesting that these factors may play a role in the occurrence of T2DM.

AIM:To investigate the mechanism through which esculetin induces ferroptosis of mouse breast cancer 4T1 cells.METHODS:Molecular docking of esculetin with p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)proteins was performed,and Kaplan-Meier curves and time-dependent receiver oper-ating characteristic curves were drawn.The 4T1 cells were divided into 6 groups,namely the control(CON),1/2 IC50,IC50,2 IC50,erastin,and capecitabine groups.The appropriate drug concentration for treating 4T1 cells was screened by CCK-8 assay.The invasion and migration abilities of 4T1 cells following esculetin treatment at the selected drug concentra-tion were analyzed by scratch test and Transwell assay.Mitochondrial morphological change were examined by electron mi-croscopy.The levels of ferroptotic cell death were then quantified by Fe2+,reactive oxygen species(ROS),malondialde-hyde(MDA),glutathione(GSH),and GPX4 assays.Western blot was performed to evaluate the protein levels of p53,SLC7A11,GPX4 and acyl-CoA synthetase long-chain family member 4(ACSL4).RESULTS:Compared with CON group,the esculetin 1/2 IC50,IC50 and 2 IC50 groups showed smaller size,increased membrane density,and decreased ridge of mitochodria,as well as decreased levels of GSH and GPX4,reduced cell invasion and migration abilities,and de-creased levels of SLC7A11 and GPX4 proteins(P＜0.05).Furthermore,these groups exhibited increased levels of Fe2+,ROS,and MDA,as well as elevated p53 and ACSL4 protein abundance(P＜0.05).CONCLUSION:Esculetin pro-motes ferroptosis of 4T1 cells through a mechanism involving the p53/SLC7A11/GPX4 regulatory axis.

Nitric oxide(NO)is an endothelial-derived relaxing factor produced by endothelial cells and catalyzed by nitric oxide synthase(NOS), which is present in many organs and tissues of the human body. NO is a key gaseous signaling molecule that mediates a variety of physiopathological processes in organisms. NO and NOS have many functions including the regulation of vascular tone, the relaxation of smooth muscle, activation of immune responses and modulation of neuro-transmission. They have been used in the treatment of diseases in a certain field. In recent years, the incidence of ophthalmic diseases has been on the rise, and the quality of life of patients has been reduced. However, treatment for most diseases is limited. It is find that NO and NOS can be detected in various tissue of ocular parts, and they are involved in the occurrence and transformation of many ocular surface and fundus diseases. This article reviews the correlation between them and ocular diseases, analyzes the mechanism and principle of the occurrence and development of diseases, and provides new ideas for the clinical treatment of ophthalmic diseases in the future.

Sleep disorders are characterized by abnormal amounts of sleep and unusual behavior during sleep.Long-term sleep disorders can lead to the disruption of normal social functioning or neurological conditions.In recent years,the role of sound wave therapy in improving sleep quality has attracted much attention.This article aims to review the research progress related to the role of sound wave therapy in enhancing sleep quality,cognitive function,and alleviating fatigue in patients with sleep disorders in hopes of contributing to clinical applications.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

On the basis of synergetic theory and complex adaptive system theory, the dialectical relationship of "industry-university-research-competition" four-in-one practical teaching was analyzed. The path of practicing "industry-university-research-competition" four-in-one practical teaching in medical universities was explored. In terms of industry, the development adheres to the principles of broad vision and selective implementation, as well as accumulating resources gradually for substantial progress. Currently, the company operates in compliance with standards, seeking steady and proactive advancement. In terms of university, we explored the combination of professional courses and entrepreneurship and innovation teaching, the combination of experimental platform and entrepreneurship and innovation incubation, and the combination of holiday practice learning and entrepreneurship and innovation practice, so as to achieve full coverage of entrepreneurship and innovation practice teaching in class and outside class. In terms of research, students participated in the faculty research projects and teams or independently applied for college student innovation and entrepreneurship projects. Scientific research has become the primary carrier of training the innovation awareness of college students. At present, we have been granted with four national college student innovation and entrepreneurship projects. In terms of competition, we have normatively participated in discipline competitions and innovation and entrepreneurship competitions, and established a complete competition system. We have won more than 200 awards in competitions at various levels. Several years of unremitting efforts to practice teaching reform have led to promising results and moderate scale of teaching practice.