1.Construction of a predictive model for poorly differentiated adenocarcinoma in pulmonary nodules using CT combined with tumor markers
Jie JIANG ; Feng LIU ; Bo WANG ; Qin WANG ; Jian ZHONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):73-79
Objective To establish and internally validate a predictive model for poorly differentiated adenocarcinoma based on CT imaging and tumor marker results. Methods Patients with solid and partially solid lung nodules who underwent lung nodule surgery at the Department of Thoracic Surgery, the Affiliated Brain Hospital of Nanjing Medical University in 2023 were selected and randomly divided into a training set and a validation set at a ratio of 7:3. Patients' CT features, including average density value, maximum diameter, pleural indentation sign, and bronchial inflation sign, as well as patient tumor marker results, were collected. Based on postoperative pathological results, patients were divided into a poorly differentiated adenocarcinoma group and a non-poorly differentiated adenocarcinoma group. Univariate analysis and logistic regression analysis were performed on the training set to establish the predictive model. The receiver operating characteristic (ROC) curve was used to evaluate the model's discriminability, the calibration curve to assess the model's consistency, and the decision curve to evaluate the clinical value of the model, which was then validated in the validation set. Results A total of 299 patients were included, with 103 males and 196 females, with a median age of 57.00 (51.00, 67.25) years. There were 211 patients in the training set and 88 patients in the validation set. Multivariate analysis showed that carcinoembryonic antigen (CEA) value [OR=1.476, 95%CI (1.184, 1.983), P=0.002], cytokeratin 19 fragment antigen (CYFRA21-1) value [OR=1.388, 95%CI (1.084, 1.993), P=0.035], maximum tumor diameter [OR=6.233, 95%CI (1.069, 15.415), P=0.017], and average density [OR=1.083, 95%CI (1.020, 1.194), P=0.040] were independent risk factors for solid and partially solid lung nodules as poorly differentiated adenocarcinoma. Based on this, a predictive model was constructed with an area under the ROC curve of 0.896 [95%CI (0.810, 0.982)], a maximum Youden index corresponding cut-off value of 0.103, sensitivity of 0.750, and specificity of 0.936. Using the Bootstrap method for 1000 samplings, the calibration curve predicted probability was consistent with actual risk. Decision curve analysis indicated positive benefits across all prediction probabilities, demonstrating good clinical value. Conclusion For patients with solid and partially solid lung nodules, preoperative use of CT to measure tumor average density value and maximum diameter, combined with tumor markers CEA and CYFRA21-1 values, can effectively predict whether it is poorly differentiated adenocarcinoma, allowing for early intervention.
2.Effect of Biejia Decoction Pill on aerobic glycolysis in hepatocellular carcinoma by regulating the protein kinase B/mammalian target of rapamycin signaling pathway
Qinwen TAN ; Jingjing HUANG ; Ruixi ZHONG ; Yuanqin DU ; Jian XU ; Jinli NONG ; Yujiao PENG
Journal of Clinical Hepatology 2025;41(2):300-306
ObjectiveTo investigate the inhibitory effect of Biejia Decoction Pill on the proliferation, migration, and aerobic glycolysis of hepatocellular carcinoma (HCC) using cell experiments, as well as related mechanisms. MethodsHuman liver cancer cell line Huh7 was selected, and Sprague-Dawley rats were randomly divided into blank serum group, inhibitor group, and high-, middle-, and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells; glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells; RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression, related proteins, and phosphorylation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. ResultsCompared with the blank serum group, the Biejia Decoction Pill groups had significant reductions in OD value, migration rate during different periods of time, glycolytic rate-limiting enzymes (hexokinase, phosphofructokinase, pyruvate kinase), and glycolytic metabolites (pyruvate, lactic acid, ATP) (all P<0.05). RT-qPCR results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR, and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT (all P<0.05). Western blot results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins, and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins (all P<0.05). ConclusionThis study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells, thereby inhibiting their proliferation and migration, possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.
3.Comparison of the clinical efficacy of super pulse thulium laser enucleation of the prostate with "open tunnel" and holmium laser enucleation of the prostate for benign prostatic hyperplasia
Jidong XU ; Ning JIANG ; Jian LI ; Zhikang CAI ; Jianwei LYU ; Chuanyi HU ; Jingcun ZHENG ; Zhonglin CAI ; Huiying CHEN ; Yan GU ; Yuning WANG ; Jiasheng YAN ; Zhong WANG
Journal of Modern Urology 2025;30(1):34-38
[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.
4.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
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.
5.Clinical Safety Monitoring of 3 035 Cases of Juvenile Feilike Mixture After Marketing in Hospital
Jian ZHU ; Zhong WANG ; Jing LIU ; Jun LIU ; Wei YANG ; Yanan YU ; Hongli WU ; Sha ZHOU ; Zhiyu PAN ; Guang WU ; Mengmeng WU ; Zhiwei JING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):194-200
ObjectiveTo explore the clinical safety of Feilike Mixture (FLK) in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21,2021 and December 25,2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved,which are distributed across 12 provinces,including one traditional Chinese medicine (TCM) hospital and 28 general hospitals. The average age among the juveniles was (4.77±3.56) years old,and the average weight was (21.81±12.97) kg. Among them,119 cases (3.92%) of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles,with 1 656 cases (54.46%). FLK was first used in 2 016 cases (66.43%),and 142 juvenile patients had special dosages,accounting for 4.68%. Among them,92 adverse drug reactions (ADRs) occurred,including 73 cases of gastrointestinal system disorders,10 cases of metabolic and nutritional disorders,eight cases of skin and subcutaneous tissue diseases,two cases of vascular and lymphatic disorders,and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea,stool discoloration,and vomiting,and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages (the use of FLK)[odds ratio (OR) of 2.642, 95% confidence interval (CI) of 1.105-6.323],combined administration: spleen aminopeptide (OR of 4.978, 95%CI of 1.200-20.655),and reason for combined administration: anti-infection (OR of 1.814, 95%CI of 1.071-3.075) were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%,and the severity was mainly mild or moderate. Generally,the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction,suggesting that FLK has good clinical safety.
6.Research progress on the mechanism of action of traditional Chinese medicine regulating Nrf2 signaling pathway to improve sepsis-induced lung injury
Yang LI ; Ruifen ZHANG ; Tingting JIA ; Hairong ZHANG ; Jian ZHAO ; Xinsheng HUANG ; Xiao LI ; Xin ZHONG
China Pharmacy 2025;36(12):1530-1535
Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome, whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress, the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine (TCM) to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients (including five types of compounds: flavonoids, terpenes, alkaloids, saponins, phenols) and 6 kinds of compound preparations (including three types of formulas: heat-clearing and detoxifying formulas, purgative formulas for promoting bowel movement, and formulas for reinforcing vital qi and consolidating the constitution) can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1, heme oxygenase-1, antioxidant response element and AMP-activated protein kinase, thereby alleviating sepsis-induced lung injury.
7.Validating the pathogenic mechanism of chronic obstructive pulmonary disease induced by negative emotions via Mendelian randomization and traditional Chinese medicine theory of emotions
Zhiying WANG ; Yun LI ; Zhixian ZHONG ; Ling XU ; Yi ZHONG ; Jian CHEN
Digital Chinese Medicine 2025;8(2):196-205
Objective:
We employed Mendelian randomization (MR) to test the traditional Chinese medicine (TCM) theory of emotional pathogenesis concept and explore the causal relationship between negative emotions and chronic obstructive pulmonary disease (COPD).
Methods:
Data of negative emotions, bronchitis, emphysema, and C-reactive protein (CRP) levels were downloaded from genome-wide association study (GWAS) public database for a two-sample MR analysis. Independent single-nucleotide polymorphisms (SNPs) associated with negative emotions, bronchitis, and emphysema were selected as instrumental variables. Primary causal estimates were derived using inverse-variance weighting (IVW), supplemented by weighted median (WM), and simple mode (SM) methods. Sensitivity analyses included MR-Egger regression and MR-PRESSO to assess pleiotropy, Cochran’s Q test for heterogeneity, and multivariate MR to adjust for smoking. Mediation analysis evaluated the role of inflammatory markers. Reverse MR was tested for bidirectional causality. Weak instrument bias was mitigated via F-statistic thresholds (> 10). All analyses were conducted in RStudio.
Results:
MR analysis identified significant causal effects of several negative emotions on COPD. Genetically, the IVW analysis of seen doctors for nerves anxiety tension or depression [ORIVW = 1.006, 95% CI = (1.002, 1.010), P = 0.002], sensitivity/hurt feelings [ORIVW = 1.024, 95% CI = (1.004, 1.044), P = 0.017], and irritability [ORIVW = 1.019, 95% CI = (1.003, 1.035), P = 0.019 were robustly associated with increased risks of COPD. No heterogeneity was detected among the different instrumental variables (IVs) for depression (P = 0.655) and irritability (P = 0.163). MR-Egger regression intercepts for all emotional exposures were close to zero and statistically non-significant, indicating no evidence of directional pleiotropy. The horizontal pleiotropy results showed that except for worry (MR-PRESSO P = 0.006), other emotion exposures confirming no substantial pleiotropic bias. Multivariable MR demonstrated that anxiety remained independently associated with COPD after adjusting for smoking (P = 0.002), while associations with other negative emotions were attenuated post-adjustment. The mediation analysis revealed that CRP mediated 3.93% of the total effect of anxiety on COPD. However, reverse MR analysis found no evidence of reverse causality.
Conclusion
This study confirmed the causal effects of negative emotions on COPD through MR analysis and revealed that negative emotions may trigger CRP production, which plays an essential mediating role in this relationship. This study provides a reliable modern theoretical basis for emotion theory in TCM.
8.Effect Mechanism and Law of Sterilization by 60Co-γ Ray Irradiation on Chemical Composition of Chinese Materia Medica: A Review
Tingting ZHU ; Jian RANG ; Rangyanpo LUO ; Rui GU ; Yue YANG ; Si LU ; Shihong ZHONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):306-314
60Co-γ ray irradiation has the unique advantages of high efficiency, strong penetration, operation at room temperature and no residue, which has been widely used in the sterilization of Chinese medicinal materials, decoction pieces, Chinese patent medicine. However, the irradiation effect may cause changes in the content of chemical components in Chinese materia medica or the emergence of new radiolysis products, leading to reduced efficacy and uncontrollable safety risks. This paper reviewed the relevant literature at home and abroad, summarized the effect of irradiation sterilization on various types of chemical compositions of Chinese medicinal materials and their preparations, and analyzed and explored the rule of change. The results showed that the content changes of various chemical components in Chinese materia medica after 60Co-γ ray irradiation sterilization varied. The contents of most flavonoids, terpenoids, phenylpropanoids and quinones decreased after irradiation, and the degree of decrease increased with the elevated irradiation dose. The contents of lignans, alkaloids, isoflavones and some terpenoids did not change significantly before and after irradiation, while the content changes of triterpenoid saponins, dihydroflavonols, chalcones, sugars and glycosides after irradiation were not yet uniform. Therefore, it is recommended to pay attention to the compositional changes of irradiated Chinese medicines, strengthen the research on the standards of irradiated Chinese medicines, and standardize the irradiation and sterilization of Chinese medicines in order to promote the healthy and rational application of irradiated Chinese medicines.
9.Analysis of the current status and countermeasures of safety content control of traditional Chinese medicine based on the revision announcement of the instruction and the national adverse drug reaction monitoring report
Jian ZHU ; Zhong WANG ; Hongli WU ; Zhiwei JING
China Pharmacy 2025;36(17):2092-2096
OBJECTIVE To provide a reference for revising the safety content of traditional Chinese medicine(TCM) instructions. METHODS A systematic analysis was conducted on the relevant announcements on the revision of TCM instruction from 2013 to 2024, including the year of publication, drug name, drug formulation, announcement release time, and the average number of revisions made to three safety contents (contraindication, adverse drug reaction, and precaution). According to the report data of national adverse drug reaction monitoring from 2013 to 2024, analyze the proportion of TCM in all adverse drug reactions, the composition ratio of adverse drug reaction of different dosage forms of drugs [TCM injection, oral TCM, other (topical) TCM]. RESULTS From 2013 to 2024, the National Medical Products Administration issued a total of 101 notices on the revision of TCM instruction, involving 241 types of TCM. Among them, there were 163 types of oral TCM, 25 types of TCM injection, and 53 types of other (topical) TCM. There were 3, 10 and 0 types of TCM injection, oral TCM, and other (topical) TCM with missing safety content, respectively. The main source of adverse drug reaction data for TCM injections was post- marketing monitoring data (accounting for 48.00%); the main source of adverse drug reaction data for oral TCM was monitoring data (accounting for 71.17%); 73.58% of other (topical) TCM did not mention the source of adverse drug reaction data. The report on national adverse drug reaction monitoring showed that the proportion of all adverse drug reactions of TCM had decreased from 17.3% in 2013 to 12.1% in 2024. Among them, the proportion of adverse drug reaction of TCM injection in the three dosage forms of TCM had decreased from 61.3% in 2015 to 24.6% in 2024, while the proportion of adverse drug reaction of oral TCM in the three dosage forms of TCM had increased from 34.7% in 2015 to 64.0% in 2024. CONCLUSIONS The risk management of TCM safety content has achieved results in China, but still faces three major challenges: strongdependence on passive monitoring, insufficient data traceability, and missing key content. It is urgent to improve safety content by dosage form, optimize data sources, and fully utilize real-world evidence to supplement safety content.
10.Correlation of serum IL-35, IgG4/IgG, TSI levels with the activity and severity of thyroid associated ophthalmopathy
Yu YAN ; Qin ZHONG ; Lei YANG ; Jian ZHANG ; Shuangle LI
International Eye Science 2025;25(10):1662-1666
AIM: To investigate the correlation of serum interleukin-35(IL-35), immunoglobulin 4/immunoglobulin(IgG4/IgG), thyroid stimulating immunoglobulin(TSI)levels with the activity and severity of thyroid associated ophthalmopathy(TAO).METHODS:Prospective study. A total of 148 TAO patients admitted to our hospital from January 2023 to July 2024 were selected as the observation group. They were assigned into an active group(75 cases)and an inactive group(73 cases)based on their activity level, and were assigned into a severe group(95 cases)and a mild group(53 cases)based on the severity of their condition; another 148 healthy patients who underwent physical examinations were regarded as the control group. The levels of IL-35, IgG4/IgG, and TSI in serum were compared between the two groups. The correlation between serum IL-35, IgG4/IgG, and TSI levels and TAO activity and severity of illness were analyzed. A multivariate Logistic regression was performed to analyze the influencing factors of TAO patients developing severe symptoms. ROC curve was applied to analyze the diagnostic value of serum IL-35, IgG4/IgG, and TSI levels for the development of severe TAO in patients.RESULTS: Compared with the control group, the serum IL-35 level in the observation group was significantly lower, while IgG4/IgG and TSI levels were significantly higher(all P<0.01). Compared with non-active TAO patients, active TAO patients had significantly lower serum IL-35 level and significantly higher IgG4/IgG and TSI levels(all P<0.01). Compared with the mild TAO patients, severe TAO patients had significantly lower serum IL-35 level and significantly higher disease duration, IgG4/IgG, and TSI levels(all P<0.01). The serum IL-35 level was negatively correlated with TAO activity and disease severity(r=-0.529, -0.554, both P<0.01), while serum IgG4/IgG level was positively correlated with TAO activity and disease severity(r=0.625, 0.663, both P<0.01). Serum TSI levels were positively correlated with TAO activity and disease severity(r=0.594, 0.607, both P<0.01). Multivariate Logistic regression analysis showed that serum IL-35, IgG4/IgG, and TSI levels were all factors influencing the progression of TAO patients to severe disease(all P<0.01). The areas under the curve(AUC)for diagnosing the progression of TAO patients to severe disease using serum IL-35, IgG4/IgG, and TSI levels were 0.868, 0.859, and 0.830, respectively. The combined AUC for the three markers was 0.955, significantly higher than that of each individual marker(Zthree factors combination-IL-35=2.893, Zthree factors combination-IL-35=3.510, Zthree factors combination-IL-35=4.157, P=0.004, <0.01, <0.01).CONCLUSION: Serum IL-35 level is significantly downregulated in TAO patients, while IgG4/IgG and TSI levels are significantly upregulated. The levels of IL-35, IgG4/IgG, and TSI are correlated with the activity and severity of TAO, and their combination has high diagnostic value for TAO developing into severe.

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