With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

In the case of extremely shortage of donor kidney sources, the number of Expanded Criteria Donors (ECD) with relatively poor kidney quality and transplantation effect is increasing. In order to alleviate the contradiction between supply and demand by using transplantable kidneys as much as possible and avoid the failure or poor effect of transplantation caused by poor quality kidneys, the quality assessment and evaluation criteria of ECD kidney have become a research hotspot in the field of kidney transplantation. This paper analyzed the possible ethical defects in the research process, and put forward some suggestions for the transplantation team to strictly follow the ethical principles of "no harm", "beneficial" and "informed consent", and the organ transplantation ethics committee to pay attention to the ethical review of the quality evaluation process of ECD donor kidney.

Objective:To explore the effect of TP53 mutation variant allele frequency(VAF)on the prognosis of diffuse large B-cell lymphoma(DLBCL)patients.Methods:This study included 155 patients with DLBCL who were first diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from March 2009 to March 2022. Complete clinical data and paraffin-embedded tumor tissue samples were obtained,and DNA was extracted from tumor tissues.The gene mutation profile of DLBCL patients was detected and analyzed by second-generation sequencing technology.Kaplan-Meier method was used to analyze the mutation status of TP53 gene and the relationship between mutation VAF and OS.Cox regression univariate and multivariate analysis was use to analyze the independent factors affecting OS.A nornogram model for predicting 1,3,and 5 years OS in DLBCL patients were established to evaluated the performance of the model based on C-index and calibration curves.Results:The average value of TP53 mutation VAF in male DLBCL patients was significantly higher than that in female patients (P<0.05 ).Patients with TP53 mutantion had shorter OS than those with wild-type patients (P=0.030).The optimal VAF threshold for TP53 mutation based on OS stratification was 33.61％(P<0.001),and patients with TP53 mutation VAF≥34％had shorter OS than those with TP53 mutation VAF<34％and wild-type patients (P<0.001).Multivariate Cox analysis showed that TP53 mutation VAF≥34％ was an independent poor predictor of OS (HR=4.05,P<0.001),and IPI score ≥3 was an independent predictor of OS poor (HR=2.27,P=0.008).In combination with factors with independent prognostic significance obtained from multi-factor analysis,we constructed a nomogram model for predicting 1-year,3-year,5-year OS in DLBCL patients.The results showed that the C index of TP53-mutated VAF combined with IPI model was 0.743,which predicted the value of 1-year,3-year,and 5-year OS in DLBCL patients.Calibration curves show that the model has good agreement between predicted and actual survival of DLBCL patients at 1-year,3-year,and 5-year. Conclusion:TP53 mutant VAF has prognostic value in DLBCL patients,and TP53 mutant VAF≥34％ is an independent risk factor for OS in DLBCL patients.The prognosis model of TP53 mutation VAF combined with IPI nomogram constructed in this study has good predictive performance for DLBCL patients.

Objective:Rejection remains the most important factor limiting the survival of transplanted kidneys.Although a pathological biopsy of the transplanted kidney is the gold standard for diagnosing rejection,its limitations prevent it from being used as a routine monitoring method.Recently,peripheral blood lymphocyte subpopulation testing has become an important means of assessing the body's immune system,however,its application value and strategy in the field of kidney transplantation need further exploration.Additionally,the development and utilization of routine test parameters are also important methods for exploring diagnostic strategies and predictive models for kidney transplant diseases.This study aims to explore the correlation between peripheral blood lymphocyte subpopulations and T cell-mediated rejection(TCMR)and antibody-mediated rejection(ABMR),as well as their diagnostic value,in conjunction with routine blood tests. Methods:A total of 154 kidney transplant recipients,who met the inclusion and exclusion criteria and were treated at the Second Xiangya Hospital of Central South University from January to December,2021,were selected as the study subjects.They were assigned into a stable group,a TCMR group,and an ABMR group,based on the occurrence and type of rejection.The basic and clinical data of these recipients were retrospectively analyzed and compared among the 3 groups.The transplant kidney function,routine blood tests,and peripheral blood lymphocyte subpopulation data of the TCMR group and the ABMR group before rejection treatment were compared with those of the stable group. Results:The stable,TCMR group,and ABMR group showed no statistically significant differences in immunosuppressive maintenance regimens or sources of transplanted kidneys(all P>0.05).However,the post-transplant duration was significantly longer in the ABMR group compared with the stable group(P<0.001)and the TCMR group(P<0.05).Regarding kidney function,serum creatinine levels in the ABMR group were higher than in the stable group and the TCMR group(both P<0.01),with the TCMR group also showing higher levels than the stable group(P<0.01).Both TCMR and ABMR groups had significantly higher blood urea nitrogen levels than the stable group(P<0.01),with no statistically significant difference between TCMR and ABMR groups(P>0.05).The estimated glomerular filtration rate(eGFR)was lower in both TCMR and ABMR groups compared with the stable group(both P<0.01).In routine blood tests,the ABMR group had lower hemoglobin,red blood cell count,and platelet count than the stable group(all P<0.05).The TCMR group had higher neutrophil percentage(P<0.05)and count(P<0.05)than the stable group,and the ABMR group had a higher neutrophil percentage than the stable group(P<0.05).The eosinophil percentage and count in the TCMR group were lower than in the stable and ABMR groups(all P<0.05).Both TCMR and ABMR groups had lower basophil percentage and count,as well as lower lymphocyte percentage and count,compared with the stable group(all P<0.05).There were no significant differences in monocyte percentage and count among the 3 groups(all P>0.05).In lymphocyte subpopulations,the TCMR and ABMR groups had lower counts of CD45+cells and T cells compared with the stable group(all P<0.05).The TCMR group also had lower counts of CD4+T cells,NK cells,and B cells than the stable group(all P<0.05).There were no significant differences in the T cell percentage,CD4+T cell percentage,CD8+T cell percentage and their counts,CD4+/CD8+T cell ratio,NK cell percentage,and B cell percentage among the stable,TCMR,and ABMR groups(all P>0.05). Conclusion:The occurrence of rejection leads to impaired transplant kidney function,accompanied by characteristic changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations in kidney transplant recipients.The different characteristics of changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations during TCMR and ABMR may help predict and diagnose rejection and differentiate between TCMR and ABMR.

Objective To explore the effect of quercetin combined with iron death inhibitor Ferrostain-1 on oxalate-induced HK-2 cell injury.Methods HK-2 cells were randomly divided into control group(normal cultured cells),model group(0.5 mmol·L-1 calcium oxalate crystals),quercetin group(0.5 mmol·L-1 calcium oxalate crystals+100 μmol·L-1 quercetin),inhibitor group(0.5 mmol·L-1 calcium oxalate crystals+8 μmol·L-1 Ferrostain-1)and combination group(0.5 mmol·L-1calcium oxalate crystals+100 μmol·L-1quercetin+8 μmol·L-1 Ferrostain-1).Cell counting kit-8(CCK-8)assay was used to detect cell survival rate;Western blot was used to detect iron death related protein expression such as glutathione peroxidase 4(GPX4);flow cytometry and Tunel assay were used to detect cell apoptosis,and assay kit was used to detect cellular iron ions and antioxidant levels.Results The cell survival rates of control group,model group,quercetin group,inhibitor group and combination group were(100.00±2.55)％,(54.49±4.11)％,(64.26±6.30)％,(58.03±3.04)％and(79.37±4.29)％,respectively;GPX4 protein expression levels were 0.98±0.11,0.33±0.05,0.56±0.05,0.78±0.07 and 1.11±0.11,respectively;cell apoptosis rates were(4.15±0.28)％,(23.12±2.49)％,(17.28±1.07)％,(15.08±1.41)％and(8.95±0.75)％,respectively;Fe2+levels were(100.00±0.87)％,(162.55±14.70)％,(149.09±9.50)％,(144.95±11.12)％and(131.76±12.18)％,respectively;superoxide dismutase(SOD)levels were(58.67±3.46),(21.56±1.32),(33.60±2.03),(35.15±3.02)and(44.27±3.89)U·mL-1,respectively.The above indicators of the model group were compared with the control group,and the above indicators of the quercetin group,inhibitor group,and combination group were compared with the model group,the above indicators of the combination group were compared with the quercetin group,and inhibitor group,all they all showed statistical significance(all P＜0.05).Conclusion Iron death inhibitors can enhance the inhibitory effect of quercetin in vitro on oxalate-induced renal tubular epithelial cell injury.

Objective To prepare paclitaxel-natural borneol complex,and to explore the prescription and preparation process of paclitaxel-natural borneol complex drug-loaded submicroemulsion,and its in vitro anti-tumor effect.Methods The Paclitaxel-natural borneol complex was prepared by grinding method and identified by Fourier Transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC).The compound drug-loaded submicroemulsion was prepared using a two-step high-pressure emulsification method.The single-factor investigation and the orthogonal experimental design were applied to optimize the formulation and preparation process.MTT assay,cell cloning assay,and cell scratch assay were used to evaluate the effect of this preparation on HCT-116 cells.Results The infrared spectral absorption peaks of taxol-natural borneol complex at 3 312.76 cm-1 and 3 513.92 cm-1 disappeared,and DSC analysis showed that a new absorption peak of taxol-natural borneol complex appeared at 154.56 ℃,indicating that taxol be coupled with natural borneol to form a new complex.The optimal prescription was 0.44％active pharmaceutical ingredient[paclitaxel-natural borneol(1∶3)],10％medium chain triglyceride,3％emulsifier[egg yolk lecithin-Poloxam 188(1∶2)],2％glycerol,0.3％oleate.The optimal process was emulsification at 80 ℃,60 MPa high pressure homogenization 10 times.The half inhibitory concentration(IC50)was 0.75 μg·mL-1 by MTT asssy in cell.In the cell cloning assay,the scratch healing area of blank control group,paclitaxel raw material and paclitaxel/natural borneol submicroemulsion were(36.44±3.35)％,(13.59±9.28)％,(8.30±4.09)％,respectively.The results were statistically significant(P＜0.05).In the plate cloning experiment,the cell cloning rates of blank control group,paclitaxel bulk drug group and submicroemulsion group were(37.92±0.729)％,(9.16±1.335)％and(3.36±1.065)％,respectively,the differents were statistically significant(P＜0.05).Conclusion This submicroemulsion has reasonable prescription,feasible process and good stability.Cell experiments showed that the submicronemulision effectively inhibits the proliferation and migration of HCT-116 cells,suggesting its potential as a promising antitumor agent.

Objective:To investigate the expression of p21-activated kinase 2 (PAK2) in laryngeal squamous cell carcinoma and its relationship with the clinicopathological characteristics and chemosensitivity of patients.Methods:Transcriptome sequencing (RNA-seq) data for laryngeal squamous cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA) database, and 123 patients were included in the study (12 cases had cancer tissues and normal tissues data, and the remaining 111 only had cancer tissues data). Differential expression of PAK2 in cancer and para-cancer tissues was analyzed by using R software, and the potential function of PAK2 in laryngeal squamous cell carcinoma was investigated by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database signaling pathway enrichment. A total of 34 patients with primary laryngeal squamous cell carcinoma tissues and corresponding para-carcinoma 34 tissue specimens who underwent surgical resection were retrospectively selected from Chaoyang Central Hospital between April 2016 and June 2021, and 20 cases of normal laryngeal mucosa tissues were selected as the controls. Immunohistochemistry was used to detect the expression of PAK2 in various tissues, and its correlation with clinicopathological factors was analyzed. A total of 35 supraglottic primary laryngeal squamous cell carcinoma patients were retrospectively collected before induction chemotherapy during the same period, including 20 patients sensitive to chemotherapy and 15 patients resistant to chemotherapy. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of PAK2 mRNA in cancer tissues.Results:Analysis of TCGA database data showed that PAK2 expression was increased in cancer tissues compared with that in para-cancer tissues ( P = 0.012); KEGG database signaling pathways showed that the high expression of PAK2 in laryngeal squamous cell carcinoma was related to signal transduction pathways, cell cycle, and cancer. Immunohistochemistry showed that the proportion of PAK2 positive in 34 cases of laryngeal squamous cell carcinoma tissues was higher than that in adjacent tissues and normal tissues [58.82% (20/34) vs. 0.03% (1/34), 0 (0/20), all P < 0.001]. There were statistically significant differences in the proportion of PAK2 positive patients stratified with different degrees of differentiation [high differentiation vs. low or middle differentiation: 33.33% (6/18)vs. 87.50% (14/16)], lymph node metastasis [presence vs. absence: 90.91% (10/11) vs. 43.48% (10/23)], TNM staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 82.35% (14/17) vs. 35.29% (6/17)] (all P < 0.05), and PAK2 positive patients were not associated with clinical type, tumor size, smoking history, drinking history, and age (all P > 0.05). qRT-PCR showed that the relative expression level of PAK2 mRNA in the chemotherapy-resistant group was higher than that in the chemotherapy-sensitive group (3.89±0.12 vs. 0.78±0.23, P < 0.001). Conclusions:The expression level of PAK2 in laryngeal squamous cell carcinoma tissues is increased, and the high expression of PAK2 is closely related to the malignant clinical characteristics of patients with laryngeal squamous cell carcinoma. The high expression of PAK2 may indicate the insensitivity to traditional chemotherapy regimens, and PAK2 may be a potential gene that targets and regulates the chemosensitivity of laryngeal squamous cell carcinoma.

Background The complex and diverse occupational disease hazards in automobile manufacturing industry pose high occupational health risks to workers. Objective To explore the methods that can accurately reflect the workplace health risk grade of automobile manufacturing enterprises, and to guide enterprises to practice risk classification management. Methods Comprehensive index method, International Commission on Mining and Metals occupational health risk assessment method (ICMM method), and risk index method were used toassess health risks of occupational disease hazards in major workstations such as welding, polishing, and painting in three automobile manufacturing enterprises in Hunan Province. Kappa consistency test was used to test the grading results of the three assessment methods. The re-examine results and detection rate of contraindications of occupational health examinations in the past three years were used to verify the assessment results. Results The results of comprehensive index method showed that the hazards of each selected workstation in enterprises A and B were evaluated as grade 2-3, among which NO₂ in enterprise A was grade 3, and welding fume, NO₂, and formaldehyde in enterprise B were all grade 3. The hazards of each selected workstation in enterprise C were grade 3-4, among which NO₂ and benzene in were grade 4, and welding fume, manganese and its compounds, grinding wheel dust, and xylene were grade 3. The hazards evaluated by ICMM quantitative method were grade 2 and grade 5, among which manganese and its compounds in enterprise A and welding fume, grinding wheel dust, and benzene series in enterprise C were graded as grade 5. The hazards evaluated by risk index method were grade 1-4, among which manganese and its compounds in enterprises A and B were grade 3, and manganese and its compounds and benzene in enterprise C were grade 4. The Kappa value between comprehensive index method and ICMM method was 0.084 (P>0.05), that between comprehensive index method and risk index method was −0.046 (P>0.05), and that between ICMM method and risk index method was 0.014 (P>0.05), indicating poor consistency. By comparing the results of occupational health surveillance with the results of occupational health risk assessment, one worker was found to have occupational contraindication of manganese exposure and 1 worker was found to have excessive manganese in hair in enterprise A. However, the comprehensive index method graded low risk for manganese and its compounds in enterprise A and the result is conservative. The key workstations identified by ICMM method were consistent with the occupational health examination results, but the assessment grades were all extremely high risk, and the results were too strict. One worker was found to be contraindicated to welding fumes, and 2 polishers were found to have severe mixed pulmonary ventilation dysfunction in enterprise C. Mild and moderate pulmonary ventilation dysfunction was found to be common in welding and polishing workstations in each enterprise. The assessment results of welding fumes and grinding wheel dust by the risk index method were negligible risks, which were inconsistent with the occupational health examination results. Conclusion The comprehensive index method, ICMM method, and risk index method can basically identify workstations with serious occupational hazards, but they have certain limitations and applicability. In general, the evaluation results of the comprehensive index method were generates more consistent with the results with occupational health surveillance than the other two methods, is more comprehensive and objective in consideration, and is more suitable for health risk assessment of automobile manufacturing enterprises.

Background The mining of non-coal underground mines may come into contact with various types of dust, such as lead, zinc, copper, and non-metallic minerals. Dust of various kinds commonly exists in all aspects of mining and selection, and is one of the main occupational hazard groups in non-coal underground mines. Objective To compare the application of two risk assessment methods in the occupational health risk assessment of productive dust in non-coal underground mines, and to provide a reference for the selection of dust hazard health risk assessment methods and the management of dust hazards in non-coal mines. Methods A field investigation of the dust hazards of three typical non-coal underground mining enterprises (lead-zinc mines, copper mines, and fluorite mines) was carried out, and the comprehensive index method and the occupational health risk assessment method from the International Council on Mining and Metals (ICMM) were used to perform risk assessments. The comprehensiveindex method considers the following factors: dust monitoring data, the aerodynamic diameter of dust, hazard control measures, occupational health management, daily usage, and daily exposure time to determine exposure levels. The ICMM method determines the risk level based on the consequences caused by dust, exposure probability, exposure time, and uncertainty coefficient. Kendall consistency test was used to compare agreement between the results generated by the two methods. Results The results generated by the comprehensive index method were as follows: level 3 (medium risk) or level 4 (high risk) for silica dust or lead dust; level 1 (negligible risk) or level 2 (low risk) for other dust (dust with free SiO₂ content<10% and containing lead, zinc, and copper, using other dust limit values for comparison), fluorspar mixed dust, fluorine and its compounds, zinc oxide, and copper dust. The risk levels graded by the ICMM method were as follows: level 4 (very high risk) and level 3 (high risk) for exposure to silica dust and lead dust, respectively, and level 1 (tolerable risk) or level 2 (potential risk) for exposure to other dust (dust with free SiO₂ content <10% and containing lead, zinc, and copper, using other dust limit values for comparison), fluorspar mixed dust, fluorine and its compounds, zinc oxide, and copper dust. The consistency level between the results graded by the two methods was very high (Kendall W coefficient=0.974, P < 0.05). Conclusion For the occupational health risk assessment of productive dust in non-coal underground mines, the consistency level of risk assessment results between the ICMM method and the comprehensive index method is very high. The ICMM method is more convenient to operate and should be preferred in assessing health risks of dust hazard in non-coal underground mines.