Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamy-cin(mTOR)signaling pathway is an important regulating pathway for metabolism,proliferation and survival in cells,and plays a pivotal role in maintaining cellular homeostasis.This signaling pathway participates in the occurrence and development process of multiple diseases by mediating the cellular autophagy,such as tumors,neurodegenerative disorders(ND)and metabolic diseases.This paper reviews the role of PI3K/Akt/mTOR signaling pathway in autophagy regulation in order to better understand the regulatory mechanisms of cellular metabolism and survival,moreover investigate the role of this signal pathway in multiple diseases and direc-tion of the future study to provide reference for explore the new disease treatment methods.

Objective:To establish ultra performance liquid chromatography (UPLC) characteristic chromatogram of Pulsatilla chinensis; To provide reference for the origin identification and quality control of Pulsatilla chinensis. Methods:UPLC Method was adopted. The determination was performed on a column of Agilent SB C18 (2.1 mm×100 mm, 1.8 μm) . The mobile phase was acetonitrile-methanol (2:1) -0.1% phosphoric acid solution by fradient elution at a flow rate of 0.30ml/min. The column temperature was 30 ℃. The detection wavelength was 215 nm. The injection volume was 2 μl. The common counterfeit products and medicinal herbs of Pulsatilla chinensis from different areas were evaluated by comparison of characteristic chromatogram, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Results:There were 9 characteristic peaks in the characteristic chromatogram of Pulsatilla chinensis, and 8 common peaks were identified by high resolution mass spectrometry and comparison of reference materials. Through PCA analysis, it was possible to clearly distinguish the medicinal herbs of Pulsatilla chinensis from different areas. Combined with OPLS-DA analysis, it was found that peak 2, peak 3, peak 6 were the main markers of Pulsatilla chinensis from different producing areas. Conclusion:The established method has good specificity, repeatability and durability, and it can effectively distinguish the common counterfeits of Pulsatilla chinensis, and provide the basis of quality control and selection of origin for Pulsatilla chinensis.

Objective:To establish the ultra high performance liquid chromatography (UPLC) fingerprints of Mume flos at different flowering stages; To provide reference for the quality research of Mume flos.Methods:The fingerprints of Mume flos were established by UPLC method, and the common peaks were identified by high performance liquid chromatography high resolution mass spectrometry (LC-MS). Chemometrics analysis was carried out with the fingerprints' common peak area of plum blossom at different flowering stages as a variable. Semiquantitative analysis of changes in flavonoids and phenolic acids in Mume flos at different flowering stages was conduct using peak area calculation method.Results:Totally 31 common peaks were identified in the fingerprints of plum blossom medicinal materials at different flowering stages and 9 components were identified. Clustering analysis (HCA) and principal component analysis (PCA) both classified plum blossom medicinal herbs at different flowering stages into three categories. Among them, there were significant differences between the groups at the bud stage, blooming period, and final flowering period, while the differences between the groups at blooming period and final flowering period were relatively small. The orthogonal partial least squares discriminant analysis (OPLS-DA) screened 16 different components with VIP>1.0. The contents of phenolic acids in different flowering stages were as follows: bud stage>blooming period>final flowering period, while the contents of flavonoids were as follows: blooming period>final flowering period>bud stage.Conclusions:This method is simple and reliable, and can provide reference for the quality evaluation of plum blossom medicinal materials at different flowering stages.

ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg^-1 and 7 g·kg^-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg^-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.

Objective:To explore the regulatory effects of Qinghua Liangxue Huluo Decoction on oxidative stress and inflammation in acute radiation enteritis in rats, as well as its impact on the PI3K/Akt pathway. Methods:A total of 36 SD rats were randomly divided into four groups using block randomization, namely the control, model, low-dose group (6.17 g/kg), and high-dose (24.68 g/kg) groups, with nine rats in each group. These rats were exposed to X-ray irradiation at a dose of 17.5 Gy to induce acute radiation enteritis, followed by continuous intragastric administration for seven days pre- and post-irradiation. Seven days post-irradiation, the perianal and fecal conditions of rats in each group were observed, and rectal tissues were collected and ground. Enzyme-linked immunosorbent assay (ELISA) was employed to assess the activity of superoxide dismutase (SOD), catalase (CAT) expression, and malondialdehyde (MDA) levels indicative of lipid peroxidation. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to analyze the mRNA expression of tumor necrosis factor-ɑ (TNF-ɑ), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the rectal tissues of each group. Additionally, Western blot was conducted to examine the expression of proteins associated with the PI3K/Akt signaling pathway in rectal tissues. The IEC-6 cells were categorized into the control, radiation, blank, and drug administration groups, with all these groups except for the control group subjected to 10 Gy single irradiation. ELISA was then employed to determine the concentrations of SOD, CAT, MDA, TNF-ɑ, IL-6, and IL-1β in cell supernatants, while Western blot was utilized to assess the expression of PI3K/Akt signaling pathway-related proteins in each group.Results:Compared to the model group, rats in the low-dose and high-dose groups exhibited a trend toward normal perianal and fecal conditions, increased SOD activity ( t = 4.86, 8.50, P < 0.05), elevated CAT expression ( t = 8.72, 14.28, P<0.05), and decreased MDA level ( t = 6.94, 10.66, P < 0.05). Furthermore, the mRNA expression of TNF-ɑ, IL-6, and IL-1β in rectal tissues was significantly inhibited in both low-dose and high-dose groups ( t = 5.60, 2.95, 4.31, 9.16, 4.66, 13.35, P < 0.05), along with lower p-PI3K/PI3K and p-Akt/Akt ratios in rectal tissues compared to the model group ( t = 22.35, 13.56, 18.23, 13.85, P < 0.05). Compared to the radiation group, the drug administration groups (10% drug-containing serum) exhibited increased SOD and CAT expressions ( t = 6.85, 10.44, P < 0.05), as well as decreased MDA expression ( t = 10.44, P < 0.05), in the supernatant. Furthermore, compared to the radiation group, this group displayed significantly inhibited TNF-ɑ, IL-6, and IL-1β concentrations in the cell supernatant ( t = 12.07, 6.87, 14.80, P < 0.05), while lowering p-PI3K/PI3K and p-Akt/Akt ratios in cells ( t = 10.95, 5.59, P < 0.05). Conclusions:Qinghua Liangxue Huluo Decoction demonstrates the potential for mitigating oxidative stress-induced injury and suppressing the expressions of inflammatory factors in rats with acute radiation enteritis. The mechanism behind the potential is likely associated with the negative regulation of the PI3K/Akt signaling pathway.

The most prevalent kind of renal calculi,calcium oxalate(CaOx),is characterized by its propensi-ty for recurrence in the urinary system.The development of CaOx renal calculi is greatly affected by macrophage polariza-tion.Particular oxalate causes an imbalance in macrophage polarization,which skews the M1/M2 ratio and makes it easier for CaOx crystals to accumulate in the kidneys and grow into calcium plaques in the renal papilla.Notably,M2 macro-phages can prevent CaOx renal calculi by consuming crystals and reducing inflammatory stress.As a result,immunothera-peutic techniques that alter M1 and M2 macrophage polarization are extremely promising for preventing CaOx renal calcu-li.To clarify the respective roles of M1 and M2 macrophages in the formation of CaOx crystals and provide insights for de-veloping immunotherapeutic interventions against CaOx renal calculi,this review summarizes the mechanisms underlying macrophage polarization in the genesis of CaOx renal calculi.

Objective To analyze and identify the volatile constituents in different parts(flowers,stems and leaves)of Huai chrysanthemumin,and to lay a theoretical foundation for the comprehensive utilization for it.Methods The volatile oil in different parts of Huai chrysanthemumin were extracted by hydrodistillation,respectively.Their constituents were analyzed by gas chromatography-mass spectrometry(GC-MS).The compounds were identified by library search and literature screening.The relative percentage of each compound was obtained by the area normalization method.The differences in their chemical compositions were analyzed by Venn diagram,principal component analysis(PCA)and cluster heat map analysis.Results A total of 62 volatile chemical components were identified from different parts of Huai chrysanthemumin,including monoterpenes,sesquiterpenes,and their derivatives,as well as a small amount of aliphatic compounds.32,42 and 40 volatile components were detected from the flowers,stems and flowers,respectively.Furthermore 17 volatile components were shared by three parts,whereas 5,6 and 16 volatile components were unique to the flowers,stems and leaves,respectively.The results of stoichiometric analysis showed that both PCA and cluster heat map analysis could separate the flowers,stems and leaves,and their volatile components were different.Conclusion The types and contents of the volatile oil in the stems,leaves and flowers of Huai chrysanthemumin have certain variability,which provide a scientific basis for the further medicinal or industrial exploitation of different parts of Huai chrysanthemumin.

Objective:To evaluated the safety and feasibility of dissection of lymph nodes posterior to right recurrent laryngeal nerve (ⅥB compartment) in endoscopic thyroidectomy through gasless axillary posterior approach.Methods:A total of 350 cases with right lobe papillary thyroid carcinoma (PTC) who underwent endoscopic lobectomy, isthmusectomy and central compartment neck dissection via gasless axillary posterior approach based at the Department of General Surgery, Nanfang Hospital, Southern Medical University from June 2020 to December 2022 were retrospectively analyzed. Summarize the clinical, pathological characteristics, and postoperative complications of the patients. SPSS 25.0 was used for statistical analysis of the data.Results:All 350 patients underwent endoscopic surgery successfully, with no conversion to open surgery. There were 303 females and 47 males, with an average age of (36.3±9.2) years. Of those, 287 patients were in pT1a stage, 62 in pT1b stage, and one patient in pT2 stage. There was no T3 or T4 stage patient. The mean numbers of yielded lymph nodes in right central compartment and ⅥB compartment were 8.11±4.65 (range, 1-31) and 2.62±1.86 (range, 1-12), respectively. ⅥB compartment metastasis was detected in 52 (14.86%) of 350 patients. The incidence of transient recurrent laryngeal nerve injury was 0.86%(3/350). Postoperative hematoma occurred in three patients (0.86%).Conclusion:The dissection of ⅥB compartment in endoscopic thyroidectomy through gasless axillary posterior approach is safe and feasible in selected PTC patients

Objective To understand the carrying situation and common variation of pathogenic genes of single gene hereditary disease in childbearing age population in Anhui province,to explore the establishment of clinical application network and referral model of carrier screening in Anhui province,and to explore the application value of expansible carrier screening(expanded carrier screening,ECS)in clinic.Methods Samples were collected from 604 individuals of childbearing age,all exhibiting a normal phenotype and a family history of inherited dis-ease.These samples were obtained during the first trimester or early stages of pregnancy(≤13+6 weeks).Based on high-throughput sequencing and special PCR analysis techniques,pathogenic variants associated with 220 disea-ses were detected,and related genes were detected in the spouses of positive carriers.Results As of May 16,2023,604 tested samples had been collected,and 340 carriers of the target disease had been detected;The posi-tive rate of pathogenic variation detection was 56.29％ ;A total of 499 pathogenic variants were detected,with each tested individual carrying 0-5 variants;216 cases,accounting for 35.76％ ,carried a single gene recessive dis-ease pathogenic variation,which was the most common.There were 95 cases carrying two types of single gene re-cessive genetic disease pathogenic variation,accounting for 15.73％ .As of now,302 couples have been reported,and a total of 7 high-risk couples have been found through screening,with a high-risk rate of 2.32％ .There are a total of 5 pairs with autosomal recessive genetic pattern(both spouses carry the same pathogenic gene),and 2 pairs with X-linked genetic pattern(the female carries the X-linked pathogenic gene).Conclusion In this study,we obtained the overall carrier and clinical application of target diseases as well as the carrier rates of causative genes of common single-gene genetic diseases in 604 subjects who underwent ECS testing,which could provide scientific guidance for the establishment of a clinical application network and referral model for carrier screening in Anhui Province.