Objective To explore the therapeutic material basis and antitussive mechanism of Ganke Formula.Methods Ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF/MS)technology was used to analyze and identify the components of Ganke Formula in serum.30 rats were randomly divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,6 rats per group.Acute bronchitis rat model was established by smoke inhalation and cold stimulus.The experimental-L,-M,-H groups were respectively given 1.86,4.66,9.32 g·kg-1(crude drug/weight)dose of Ganke Formula per day by intragastric administration for 7 days.The control group and model group were given the equal amount of normal saline.The contents of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in rat lung tissue were determined by enzyme-linked immunosorbent assay.The expressions of phosphatidylinositol 3-kinase(PI3K)and phosphorylated protein kinase B(p-Akt)in lung were detected by Western blotting.Results Twenty-six absorbed components have been identified by UPLC-Q-TOF/MS.The contents of IL-1β in control group,model group,experimental-M,-H group were(57.80±7.67),(186.48±8.50),(166.05±9.90)and(143.19±6.31)pg·mL-1;TNF-α contents were(47.14±8.55),(316.22±9.49),(68.93±7.94)and(65.93±7.10)pg·mL-1;the relative expression levels of PI3K in lung tissues were 0.38±0.05,0.97±0.10,0.68±0.15 and 0.56±0.10;the relative expression levels of p-Akt were 0.34±0.14,0.93±0.05,0.63±0.16 and 0.49±0.14,respectively.Compared with the model group,the above indicators in the experimental-H group and control group were statistically different(P＜0.01 or P＜0.05).Conclusion Ganke Formula can intervene in the expression of inflammatory and immune regulatory factors by regulating PI3K/Akt signaling pathway,improve airway inflammation,and thus exert cough relieving effects.

Objective To mine and analyze the adverse event data of polatuzumab vedotin(Pola)and fam-trastuzumab deruxtecan-nxki(T-Dxd),so as to provide reference for clinical medication safety.Methods The adverse events reported from January 1,2004 to June 7,2023 were extracted based on openFDA database.The suspicious risk signals were screened by the Open Vigil 2.1 data platform and ranked by signal strength and frequency of occurrence;then ADEs were classified by reference to the MedDRA 26.0.Results A total of 7 164 and 22 870 ADE reports related to Pola and T-Dxd were obtained,and 104 and 95 suspicious ADE signals were detected,respectively.According to the signal intensity,cytomegalovirus enterocolitis(ROR=416.94)for Pola and interstitial lung disease[reporting odds ratio(ROR)=82.55]for T-Dxd ranked first,both of which were recorded in the drug instructions.According to the frequency of occurrence,the two drugs were most frequently associated with death(n=111)and nausea(n=285),respectively.The risk of Pola was associated with 12 systems/organs,of which 26 risk signals were not documented in the drug instruction,and the risk of T-Dxd was associated with 13 systems/organs,of which 18 risk signals were not documented in the drug instruction.Conclusion By tapping the ADE after real-world administration of Pola and T-Dxd,physicians are prompted to pay attention to the risk of adverse reactions in clinical use and actively take preventive and therapeutic measures to ensure the safety of patients'medication.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Plasma metabolomics combined experimental verification was employed for investigating of the hypoglycemic effect of Panax notoginseng saponins (PNS) on type 2 diabetes mellitus (T2DM) mice. Forty C57BL/6J mice were randomly divided into control and experimental groups after one week of adaptive feeding. The mice in control group were fed conventionally, and the T2DM model was established in mice of the experimental group by intraperitoneal injection of streptozotocin following twelve weeks of feeding on a high-fat diet (HFD). All experiments were approved by the Ethical Committee Experimental Animal Center of North Sichuan Medical College (NSMC2022023). After the failure cases during modeling were eliminated, the remaining mice were randomly divided into model group (T2DM), low dose [200 mg·kg^-1·d^-1] and high dose [300 mg·kg^-1·d^-1] PNS groups. Mice in normal and model groups were given equal amounts of normal saline by gavage. The mice were administered intragastrically with PNS for 6 weeks, and their body weight, food intake, water intake and fasting blood glucose (FBG) were measured weekly. Oral glucose tolerance test (OGTT) was performed at the 5th week of administration. The changes of liver functions and blood lipids were detected by collecting blood from eyeballs. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were detected in the blood and the activity of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were analyzed in the liver by kit, respectively. Subsequently, the changes in plasma endogenous metabolites from each group were determined based on metabolomics, and the pathway enrichment analysis of differential metabolites was performed using KEGG database. NF-κB signaling pathway, TNF-α and IL-6 in liver were detected by western blot, respectively. The results showed that T2DM mice were successfully constructed. High dose of panax notoginseng saponins (HPNS) can reduce the FBG in T2DM mice while low dose of PNS (LPNS) has no significant effect on FBG. HPNS improves the liver function, reduces the levels of blood lipids, TNF-α and IL-6, and increases the activity of GSH-Px, CAT and SOD in liver of T2DM mice. Metabolomics results showed that 45 metabolites were significantly changed in the plasma of model group compared with control, and 20 metabolites were significantly changed after HPNS treatment. Pathway enrichment indicated that arachidonic acid metabolism, linoleic acid metabolism, glutathione metabolism and carnitine synthesis were changed in the blood of T2DM mice, and HPNS improved the abnormal metabolism of arachidonic acid and linoleic acid in T2DM mice. Western blot showed that HPNS could inhibit the NF-κB pathway and reduce the expression of TNF-α and IL-6 in the liver of T2DM mice, suggesting that PNS may exert the antidiabetic effect by inhibiting NF-κB pathway, regulating arachidonic acid and linoleic acid metabolism to reduce inflammatory factors and oxidative stress, improve liver function in T2DM mice.

Liver is the main organ of glucose and lipid metabolism, and persistent hyperglycemia is a common cause of liver injury. Panax notoginsenosides (PNS) is the main active ingredient in Panax notoginseng, which have anti-inflammatory and antioxidant effects. In this study, quantitative proteomics combined with experimental verification was used to explore the protective effect of PNS on liver injury in type 2 diabetes mellitus (T2DM) mice and its potential mechanism. All experiments were approved by the Ethical Committee Experimental Animal Center of North Sichuan Medical College (NSMC2022023). Hematoxylin-eosin (H&E) staining and transmission electron microscopy were used to observe the effect of PNS on the histopathological changes of liver in T2DM mice. TdT-mediated dUTP Nick-end labeling (TUNEL) staining was used to analyze the effect of PNS on hepatocyte apoptosis in T2DM mice. Reactive oxygen species (ROS) and malonaldehyde (MDA) kits were used to detect the effect of PNS on oxidative damage of liver in T2DM mice. Subsequently, proteomics profiling of mice in T2DM and T2DM+PNS groups were investigated based on quantitative proteomics. Differentially expressed proteins were screened out according to fold change and significance level in T2DM and T2DM+PNS groups, respectively. Pathway enrichment analysis of these differential proteins was done using GeneAnalytics database. Gene ontology analysis was conducted by Metascape database. Protein-protein interaction networks were constructed based on STRING database. Western blot was used to detect protein expression. These results showed that PNS could improve liver abnormalities, inhibit hepatocyte apoptosis, and improve the morphology of mitochondria and endoplasmic reticulum in T2DM mice. Proteome data demonstrated that 489 genes expression changed significantly in liver of T2DM mice compared with normal, and 42 ones were significantly reversed after PNS treatment and returned to normal levels. Pathway analysis showed that sterol hormone biosynthesis, adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling pathway, oxidative stress, insulin signaling, phosphatidylinositol pathway, tumor necrosis factor-α (TNF-α) mediated inflammation, insulin resistance, and mTOR signaling pathway exhibited notable changes based on pathway enrichment ratio and significance level. It is worth noting that PNS could improve the abnormal changes of AMPK, TNF-α, apoptosis and insulin pathways. Western blot manifested that PNS inhibit the expression of Bax, Grp78 and Chop, reduce ratio of cleaved casp6/casp6, increase the levels of pAMPKα, HO-1 and Nu-Nrf2 in the liver of T2DM mice. These results suggested that PNS may play protective roles in the liver of T2DM mice by inhibiting apoptosis via activating AMPK/Nrf2/HO-1 signaling pathway, alleviating oxidative stress and endoplasmic reticulum stress.

Objective To analyze the medication rules of Professor HUANG Feng for the treatment of low back pain using data mining methods.Methods The information of prescriptions for the effective cases of outpatients with low back pain treated by Professor HUANG Feng were collected and screened.Microsoft Excel 2019 was used to analyze the frequency of medication and the distribution of properties,flavors and meridian tropism of the drugs in the included prescription.IBM SPSS Modeler 18.0 was used for association rule analysis,and IBM Statistics 26.0 was used for cluster analysis.Results A total of 239 prescriptions and 75 Chinese medicines were included.There were 23 high-frequency Chinese medicines with the medication frequency being or over 20 times,and the top 10 Chinese medicines were Glycyrrhizae Radix et Rhizoma,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma,Zanthoxyli Radix,salt-processed Achyranthis Bidentatae Radix,Rehmanniae Radix,Dipsaci Radix,Coicis Semen,and Salviae Miltiorrhizae Radix et Rhizoma.The medicines were mainly warm in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of liver,stomach and spleen meridians.Among the drug combinations obtained from association rule analysis with the top 20 highest support,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma and Zanthoxyli Radix were the core drugs.Cluster analysis yielded 6 clustering combinations.Conclusion For the treatment of low back pain,Professor HUANG Feng follows the principle of"treatment adapting to the climate,individuality,and environment"and"treating the root cause of the disease",usually adopts the drugs for activating blood,moving qi and relieving pain,nourishing the liver and kidney,and also uses the medicines for replenishing qi and strengthening the spleen.The ideas of HUANG Feng for the treatment of low back pain can be used as a reference for the clinical treatment.

ObjectiveTo investigate the effect of Zuoguiwan on the ovarian function in the rat model of cyclophosphamide-induced premature ovarian failure （POF） based on the changes of ferroptosis pathway. MethodForty SD rats were randomized into blank， model， and low- and high-dose （2， 8 g·kg^-1， respectively） Zuoguiwan groups， with 10 rats in each group. The rats in the other groups except the normal group were intraperitoneally injected with CTX at a dose of 50 mg·kg^-1 on the first day and 8 mg·kg^-1 from the second day to the fifteenth day for the modeling of POF. After modeling， the rats were administrated with corresponding drugs or normal saline by gavage for four weeks. Hematoxylin-eosin staining was performed to observe the pathological changes in the ovarian tissue. The mitochondria of the ovarian tissue was observed by electron microscopy. The serum levels of follicle-stimulating hormone （FSH）， estradiol （E₂）， luteinizing hormone （LH）， anti-Mullerian hormone （AMH）， malondialdehyde （MDA）， catalase （CAT）， superoxide dismutase （SOD）， and iron ion were measured by biochemical methods and enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， ferritin heavy chain （FTH1）， and acyl-CoA synthetase long chain family member 4 （ACSL4）. ResultCompared with the blank group， the model group showcased significantly increased atretic follicles， atrophied， fragmented， and vacuolated mitochondria， and reduced， loose， and disordered cristae in mitochondria. Compared with the model group， high-dose Zuoguiwan increased mature follicles， the volume of mitochondria in the ovary， alleviated the vacuolation， and improved the number and arrangement of mitochondrial cristae. Compared with the blank group， the modeling elevated the levels of iron， MDA， FSH， and LH， up-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， decreased the activities of SOD and CAT， lowered the levels of E₂ and AMH， and down-regulated the expression of ACSL4 （P<0.05， P<0.01）. Compared with the model group， drug interventions lowered the levels of iron， MDA， FSH， and LH， down-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， increased the activity of CAT， elevated the levels of E₂ and AMH， and up-regulated the expression of ACSL4 （P<0.05， P<0.01）. ConclusionZuoguiwan may inhibit the occurrence of ferroptosis by regulating the SLC7A11/GPX4 axis， thereby improving the ovarian function of POF rats.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

OBJECTIVE To investigate the effects of polydatin （PD） on cell proliferation， migration， invasion and tumor growth of acute myeloid leukemia （AML）. METHODS Human AML cell KG-1 were divided into normal group， PD low-， medium- and high-concentration groups （10， 30， 60 μmol/L PD）， SQ22536 group [cyclic adenosine monophosphate （cAMP） inhibitor， 100 μmol/L]， high concentration of PD+SQ22536 group （60 μmol/L PD+100 μmol/L SQ22536）. The effects of PD on cell activity， apoptotic rate， invasion and migration ability， cAMP level， the expression of epithelial-mesenchymal transition （EMT） related proteins and protein kinase A （PKA） were investigated. Using BALB/c nude mice as subjects， a transplanted tumor model of AML nude mice was induced by subcutaneous inoculation of KG-1 cell suspension and then divided into control group， PD group， SQ22536 group and PD+SQ22536 group （with 6 mice in each group）. The effects of PD on tumor volume and mass were measured. RESULTS Compared with the normal group or control group， the cell viabilities， the number of migrating cells， the number of invasive cells， the relative expressions of vimentin and Snail as well as the tumor volume and mass were decreased significantly in PD groups， while the apoptotic rates， cAMP levels， the relative expressions of E-cadherin and PKA were significantly increased， with a dose-dependent manner （P＜0.05）. SQ22536 had opposite effects on cells and nude mice compared to PD， and could significantly reverse the anti-tumor activity of PD （P＜0.05）. CONCLUSIONS PD may inhibit the proliferation， migration， invasion and EMT process of KG-1 cells， induce apoptosis， and inhibit tumor growth， by activating the cAMP/PKA signaling pathway， thereby exerting anti-AML effects.