Objective : To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3) in Erastin-induced ferroptosis of acute myeloid leukemia(AML) cells and its related molecular regulatory mechanisms. Methods : Tetrazolium salt(MTS) method was used to detect the sensitivity of different AML cells to the classic ferroptosis inducer Erastin, real time quantitative polymerase chain reaction(qPCR) was used to detect the basal expression level ofLPCAT3mRNA, and the correlation between them was analyzed. Lentivirus-mediatedLPCAT3overexpression AML cell lines(OE group) and negative control lines(NC group) were constructed. After Erastin intervention, MTS, flow cytometry, and micromethods were used to detect cell viability, lipid reactive oxygen species(ROS), and Malondialdehyde(MDA), respectively. qPCR and Western blot were used to detect unfolded protein response(UPR) classic pathway signaling molecules(PERK, ATF4, GRP78, etc.) expression levels. The above ferroptosis-related indicators were detected after combined intervention with the UPR inhibitor 4-phenylbutyric acid(4-PBA), and the regulatory relationship was analyzed. Results : Four different types of AML cells had different sensitivities to ferroptosis, among which K562 cells were relatively insensitive. The IC50of the four types of AML cells to Erastin was negatively correlated with the expression level ofLPCAT3(r=-0.919,P<0.001). After Erastin intervention, the cell viability of K562 cells in the OE group was significantly inhibited by Erastin compared with the NC group(P<0.001), and the levels of lipid ROS and MDA increased(P<0.001). The results of qPCR and Western blot showed that, compared with the NC group, the mRNA and protein expression of UPR classic pathway moleculesPERK,ATF4, andGRP78mRNA and protein increased in the OE group(P<0.01). After inhibiting the UPR pathway by 4-PBA, the viability of K562 cells decreased(P<0.01), and lipid ROS and MDA levels increased(P<0.01) compared with the uninhibited state. Conclusion Overexpression ofLPCAT3can promote ferroptosis in K562 cells, and this process is negatively regulated by the classical UPR pathway PERK/ATF.

According to zang-fu （脏腑） wind-damp theory， it is believed that wind， cold， and dampness are internal pathogenic factors that， when stagnated， transform into heat and invade the zang-fu organs， leading to chronic conditions. Heat is seen as a manifestation， while cold is considered the root cause. When external factors trigger these latent pathogens， the disease of the zang-fu organs exacerbates or relapses， often presenting with a complex syndrome of cold and heat. Based on this theory， the viewpoint of "for complex syndrome of cold and heat， cold is the root" is proposed. It suggests that for diseases with a complex cold-heat syndrome， external invasion of wind， cold， and dampness are the initiating factors. During the acute phase， treatment should focus on dispelling and eliminating the pathogens to promote the expulsion of the latent wind， cold， and dampness. During the remission phase， the focus shifts to reinforcing the healthy qi and tonifying the root， allowing the cold and dampness to be cleared. Internal dampness originates from the spleen； therefore， regulating the spleen and stomach， and dispersing cold and removing dampness is the key to treating wind-damp disorders of zang-fu organs. Cold and dampness are both yin pathogens， which damage yang qi， and repeated invasions of wind， cold， and dampness obstruct the qi flow of the zang-fu organs， progressively weakening yang qi. Hence， it is necessary to protect yang qi， and thereafter dispelling cold and dampness by warming yang. The theory that "for complex syndrome of cold and heat， cold is the root" provides guidance for the clinical application and the treatment of complex and difficult diseases in traditional Chinese medicine.

ObjectiveTo investigate the potential effect of ursodeoxycholic acid （UDCA） in the prevention and treatment of COVID-19 in patients with chronic hepatitis B. MethodsClinical data were collected from 324 patients with chronic hepatitis B who were treated in Beijing Ditan Hospital， Capital Medical University， from January to December 2022， and according to whether UDCA was administered， they were divided into UDCA group and control group. The propensity score matching （PSM） method was used to balance the confounding factors such as age， sex， and chronic complications， and the two groups were compared in terms of SARS-CoV-2 infection rate， symptoms， and recovery time after COVID-19. The two groups were also compared in terms of related laboratory markers （white blood cell count ［WBC］， hemoglobin ［Hb］， platelet count ［PLT］， alanine aminotransferase ［ALT］， aspartate aminotransferase ［AST］， albumin ［Alb］， alkaline phosphatase ［ALP］， total bilirubin ［TBil］， triglyceride ［TG］， and total cholesterol ［TC］）， vaccination， and the incidence rate of liver disease symptoms after COVID-19. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of data with skewed distribution between the two groups； the chi-square test and the continuously corrected chi-square test were used for comparison of categorical data between two groups. The binary Logistic regression model was used for univariate and multivariate analyses to investigate the influencing factors for COVID-19 after matching. ResultsThere were 87 patients in the UDCA group and 237 patients in the control group， and after PSM， there were 78 patients in the UDCA group and 137 patients in the control group， with good balance between the two groups. There was a significant difference in SARS-CoV-2 infection rate between the UDCA group and the control group ［82.1% （64/78） vs 95.6% （131/137）， χ²=10.847， P=0.001］. After COVID-19， compared with the control group， the UDCA group had a significantly lower proportion of the patients with chill （10.9% vs 38.9%， χ²=16.124， P<0.001） and cough （56.3% vs 74.8%， χ²=6.889， P=0.009）. There was a significant difference between the UDCA group and the control group in the proportion of the patients with a recovery time of ≤7 days after COVID-19 （79.7% vs 61.1%， χ²=6.760， P=0.009）. Both univariate and multivariate logistic regression analyses showed that UDCA was an independent influencing factor for COVID-19 （odds ratio=0.21 and 0.17， both P<0.05）. ConclusionUDCA is an protective factor against COVID-19 in patients with chronic hepatitis B and can alleviate related symptoms to some extent and shorten the recovery time， and therefore， it has an important value in the prevention and treatment of COVID-19.

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

The Wnt signaling pathway plays an important role in maintaining liver homeostasis and liver regeneration.In healthy livers,the Wnt signaling pathway is mostly inactive,but it is continuously overactivated during cell renewal or regeneration processes,as well as in certain pathological conditions,diseases,precancerous states,and cancers.Persistent liver cell injury often leads to chronic liver diseases such as liver fibrosis,liver cirrhosis,and liver cancer.This article summarizes the basic structural features of the Wnt signaling pathway and analyzes its important role in the pathological progression of various liver diseases,so as to provide new ideas for the prevention and treatment of liver diseases in clinical practice.

Background The burden of chronic kidney diseases (CKD) is continuously increasing in the globe. Environmental factors are one of the trigger factors for chronic kidney diseases of unknown etiology (CKDu). However, the current toxicological evidence on the renal effects induced by environmental high concentrations of multiple ions in drinking water and high temperature exposure is very limited. Objective To preliminary investigate the renal effects of exposure to drinking water with environmental high concentrations of fluoride, calcium, sodium, and bromide ions alone or in combination with high temperature in mice. Methods A mouse drinking water exposure model was established using ICR male mouse (8 weeks old) with exposure to 3 mg·L⁻¹ fluoride ions, 250 mg·L⁻¹ calcium ions, 400 mg·L⁻¹ sodium ions, and 1 mg·L⁻¹ bromide ions (to mimic the high concentration of ions in the groundwater in the areas with a high prevalence rate of CKDu in Sri Lanka) and high temperature of 32 ℃. ICR male mice were randomly divided into a mixed fluoride-calcium-sodium-bromide ion and high temperature exposure group, exposure groups of each ion and high temperature alone, a fluoride-calcium-sodium ion exposure group, and a fluoride-calcium-sodium-bromide ion exposure group. In the control group, the animals were given normal purified water at room temperature of (23±2) ℃. After 12 consecutive weeks of exposure, body weights and liver (kidney) organ coefficients were determined. Assessment of renal histopathologic damage was performed by hematoxylin-eosin staining and pathology scoring. At the end of the 12-week exposure period, 24 h urine samples were collected for the measurements of creatinine (UCr), albumin (ALB), neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2-MG) levels. Cell apoptosis was assessed by TUNEL assay. Results The mice in the mixed exposure group showed a significant decrease in body weight and marked increases in the scores of renal histopathological injuries and the urinary levels of β2-MG compared to those of the control mice (P<0.05). Compared with the control group, the differences in body weight and urinary renal injury indexes of the mice in the fluoride-calcium-sodium and the fluoride-calcium-sodium-bromide ion groups (except for the decrease of the β2-MG levels in urinary in the latter group) were not statistically significant (P>0.05), but the renal histopathological injury scores were significantly increased (P<0.05). By contrast, body weights, liver (kidney) organ coefficient, and renal histopathological injury scores were comparable in the control mice and the mice fed with drinking water containing high levels of a single ion alone or housed at high temperature alone (P>0.05). Furthermore, the renal histopathological injury score showed no significant differences between the fluoride-calcium-sodium ion exposure group and the fluoride-calcium-sodium-bromide ion exposure group (P>0.05). The interaction between bromide ions and fluoride-calcium-sodium ions on renal tissue pathological damage was not statistically significant (P>0.05). Results from the TUNEL assay showed a significant increase in renal cell apoptosis in the fluoride-calcium-sodium ion exposure group (P<0.05). Conclusions Environmental high levels of mixed fluoride, calcium, and sodium ions in drinking water induce renal pathological damage in mice, which are exacerbated in combination with high temperature environment. High temperature exposure alone does not affect the pathological damage of renal tissue,

ObjectiveTo determine the syndrome of a rat model of follicular dysplasia induced by Tripterygium glycosides based on prescriptions and investigate the mechanism of traditional Chinese medicine intervention via the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/hypoxia-inducible factor-1 （HIF-1）/vascular endothelial growth factor （VEGF） pathway. MethodForty-eight rats with regular estrous cycles were randomly assigned into a normal group （n=8） and a modeling group （n=40）. The rats in the modeling group were administrated with Tripterygium glycoside suspension （75 mL·kg^-1） by gavage for 30 days. The modeled rats were assigned into model， Siwutang （3.69 g·kg^-1）， Youguiyin （3.11 g·kg^-1）， Zuoguiyin （7.29 g·kg^-1）， and Guishenwan （10.35 g·kg^-1） groups， with 8 rats in each group. The drug intervention lasted for 14 days. The changes of estrous cycle were detected by Pap staining， and a stereoscope was used to observe the morphology of the ovarian tissue. Hematoxylin-eosin staining was employed to observe the pathological changes and follicle count in the ovarian tissue. Enzyme-related immunosorbent assay （ELISA） was used to measure the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂） in the serum. Real-time fluorescence quantitative polymerase chain reaction and Western blot were employed to determine the mRNA and protein levels， respectively， of AMPK， mTOR， HIF-1， and VEGF in the ovarian tissue. ResultCompared with the normal group， the model group had a disordered estrous cycle， reduced secondary and mature follicles， increased atretic follicles， elevated FSH and LH levels， lowered E₂ level， up-regulated mRNA and protein levels of AMPK， and down-regulated mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with the model group， Guishenwan increased secondary and mature follicles， decreased atretic follicles， lowered the FSH and LH levels， elevated the E₂ level， down-regulated the mRNA and protein levels of AMPK， and up-regulated the mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with Guishenwan group， Siwutang， Youguiyin， and Zuoguiyin decreased mature follicles， increased atretic follicles （P<0.01）， elevated the LH （P<0.01） and FSH （P<0.05） levels， and lowered the E₂ level （P<0.05）. In addition， Youguiyin up-regulated the protein level of AMPK （P<0.05） and down-regulated the mRNA levels of mTOR and HIF-1 （P<0.01） as well as the mRNA and protein levels of VEGF （P<0.01）. Siwutang down-regulated the mRNA levels of mTOR and HIF-1 as well as the mRNA and protein levels of VEGF （P<0.05）. Zuoguiyin down-regulated the mRNA level of mTOR and the protein and mRNA levels of VEGF （P<0.05）. ConclusionGuishenwan may improve the ovarian function and promote follicle maturation in a rat model of follicular dysplasia by inhibiting the AMPK/mTOR/HIF-1/VEGF pathway， with the therapeutic effect superior to Zuoguiyin， Youguiyin， and Siwutang. It was hypothesized that this model presented the syndrome of kidney-essence deficiency.

Purpose To explore the differences of the accuracy of detection and recognition of thyroid nodules and the diagnostic efficacy of benign and malignant thyroid nodules via artificial intelligence(AI)ultrasound assisted systems based on different ultrasound parameters.Materials and Methods A total of 147 patients with 289 nodules who underwent thyroid surgery in the First Medical Center of Chinese PLA General Hospital from March 30,2023 to May 1,2023 were prospectively selected.Different ultrasound parameters were adjusted and the AI system was used to detect and diagnose benign and malignant thyroid nodules via each parameter.Taken pathological results as the gold standard,the accuracy of thyroid nodule detection and the accuracy of benign and malignant diagnosis under different ultrasound parameters were compared,respectively.Results Under the standard ultrasound parameters,the accuracy of AI system in detecting thyroid nodules was 94.1%,the sensitivity for benign and malignant diagnosis was 90.9%,the specificity was 79.6%,and the accuracy was 86.6%,respectively.In terms of detection accuracy,accuracy under low gain(χ2=4.453,P=0.035)and high gain(χ2=6.215,P=0.013)parameters of AI system were significantly lower than those of standard ultrasound parameters.In terms of diagnostic efficacy,specificity(χ2=4.620,P=0.032),accuracy(χ2=7.521,P=0.006),area under the curve(Z=3.102,P=0.001),high gain sensitivity(χ2=6.170,P=0.013),accuracy(χ2=4.127,P=0.042),area under the curve(Z=2.152,P=0.031)and high depth accuracy(χ2=5.011,P=0.025),area under the curve(Z=2.420,P=0.015)of low gain were all significantly reduced compared to standard ultrasound parameters,with statistical differences.Conclusion When using the AI system to assist in the examination of thyroid nodules,attention should be paid to the adjustment of ultrasound instrument parameters.Improper parameter adjustment may reduce the AI system's ability to detect thyroid nodules and the accuracy of benign and malignant diagnosis.

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120-/-)and THP-1 cells. Method Six-eight-week-old C6orf120-/-and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors. Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68+CD86+M1 macrophages from the liver and spleen in the C6orf120-/-rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68+CD80+M1 macrophages and inhibited the CD68+CD206+M2 phenotype. Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120-/-rats.

ObjectiveTo explore the recognition of oral breath odor map of chronic atrophic gastritis （CAG） patients with dampness-heat syndrome by electronic nose technique. MethodsPatients with chronic gastritis were recruited， including 60 cases in CAG group of dampness-heat syndrome， 50 cases in CAG group of non-dampness-heat syndrome， 60 cases in chronic non-atrophic gastritis （CNAG） group of dampness-heat syndrome， 50 cases in CNAG group of non-dampness-heat syndrome， and 30 cases of healthy volunteers were selected to set up the health control group. Ten cases in the CAG dampness-heat group and 50 cases in the CAG non-dampness-heat group were selected to form the CAG group， and 10 cases in CNAG dampness-heat group and 50 cases in CNAG non-dampness-heat group were selected to form the CNAG group. In addition to the health control group， the remaining patients were tested for Helicobacter pylori （Hp）； the electronic nose （GISXM-MQWA01） was used to collect the oral breath odor of all the participants to draw the mapping， and amplitudes and slopes of each curve （including curves A， B， C， D， E， F， G， H， I， J） of the oral odor mapping of health control group， CAG group， CNAG group， CAG dampness-heat group， CAG non-dampness-heat group， and CNAG dampness-heat group was compared. The modified transformer model was used to classify the odor mapping characteristics， and the confusion matrix method was used to evaluate the classification model， with metrics including accuracy and area under ROC curve （AUC）. ResultsThe Hp positivity rate in CAG dampness-heat group was 80.00% （48/60）， CAG non-dampness-heat group was 62.00% （31/50）， CNAG dampness-heat group was 46.67% （28/60）， and CNAG non-dampness-heat group was 42.00% （21/50）； the difference in Hp positivity rate between CAG dampness-heat group and CAG non-dampness-heat group was statistically significant （P＜0.05）. The amplitudes of response curves A， B， C， D， F， G， and I， and slopes of A and F in the odor mapping of the CAG group were lower than those in health control group， while the amplitude and slope of curve E were higher than those in the health control group and CNAG group （P＜0.05 or P＜0.01）； The amplitude of the response curves A， B， C， D， F， G， and I， and slopes of A， D， and F in the CNAG group were lower than those in the health control group （P＜0.05 or P＜0.01）. The amplitude of response curve D and slope of response curve J in the odor mapping of the CAG dampness-heat group were higher than those in CNAG dampness-heat group， the amplitude of curve F was lower than that in CAG non-dampness-heat group， and the amplitude of curve H and slopes of curve A， H， and J were higher than those in CAG non-dampness-heat group （P＜0.05）. The recognition accuracy of CAG group and health control group reached 77.78%， AUC = 0.88； the recognition accuracy of CAG group and CNAG group was 69.44%， AUC = 0.61； the recognition accuracy of CAG dampness-heat group and CAG non-dampness-heat group reached 75.8%， AUC=0.70. ConclusionElectronic nose technology can make a more accurate identification of the oral breath odor in CAG patients with dampness-heat syndrome， with a decrease in the amplitude of the curve F and an increase in the amplitude of the curve H and in the slopes of the curves A， H， and J may as the characteristics of their odor mapping.