Objective:To investigate the predictive value of preoperative 18F-FDG PET/CT imaging for postoperative recurrence and metastasis in patients with stage Ⅰ solid and subsolid non-small cell lung cancer (NSCLC). Methods:This retrospective analysis included 139 patients (71 males, 68 females; age (62.1±9.0) years) with ⅠA1-ⅠB stage solid and subsolid NSCLC who underwent surgery and preoperative 18F-FDG PET/CT imaging at the Fourth Hospital of Hebei Medical University from December 2020 to December 2022. Patients were randomly divided into a training group and a validation group in a ratio of 7∶3, and SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG), clinical data, and disease-free survival (DFS) were collected. ROC curves were generated for the training group to determine the optimal cut-off values of SUV max, MTV, and TLG for predicting recurrence and metastasis. The Cox proportional hazards regression model was used to identify factors predicting DFS and to establish a prediction model, which was then validated in the validation group. The prognostic efficacy of the model was evaluated by using the concordance index (C-index). Results:Of 139 patients, 97 were in the training group and 42 were in the validation group, with 23 experienced recurrences during the follow-up period, including 18 in the training group and 5 in the validation group. The optimal cut-off values of SUV max, MTV and TLG for predicting tumor recurrence and metastasis in the training group were 5.85, 5.55cm 3, and 12.55g, respectively. Univariate analysis showed that SUV max (hazard ratio ( HR)=4.83, 95% CI: 1.81-12.89, P=0.002), MTV ( HR=6.90, 95% CI: 2.27-20.98, P<0.001), and TLG ( HR=5.77, 95% CI: 1.90-17.57, P=0.002) were predictive factors for postoperative recurrence and metastasis, while multivariate analysis identified MTV ( HR=4.67, 95% CI: 1.42-15.36, P=0.011) as an independent predictive factor. The prognostic C-index (95% CI) of models in training group and validation group were 0.814(0.745-0.882) and 0.810(0.624-0.995). Conclusions:Preoperative 18F-FDG PET/CT imaging has significant predictive value for postoperative recurrence and metastasis risk in patients with stage Ⅰ solid and subsolid NSCLC. MTV can be considered as an independent prognostic factor for preoperative recurrence and metastasis.

Objective To investigate the preoperative prediction of the expression level of programmed cell death ligand 1(PD-L1)in non-small cell lung cancer(NSCLC)by a nomogram model constructed with clinical data,conventional CT signs and spectral CT parameters.Methods A retrospective analysis was conducted on 52 patients with pathologically confirmed NSCLC and undergoing preoperative spectral CT examination.The patients were categorized into positive and negative groups according to PD-L1 expression level,and their clinical data,conventional CT signs and spectral CT parameters were collected.Specifically,clinical data included gender,age,Ki-67 and tumor markers;conventional CT signs included tumor density,margins,calcification,spiculation,lobulation,pleural indentation and cavitation;and spectral CT parameters measured in the arterial and venous phases included effective atomic number(Eff-Z),iodine concentration(IC),water concentration(WC)and normalized iodine concentration(NIC).Intergroup differences were analyzed,and multivariate Logistic regression was used to identify independent predictors and establish the prediction model which was evaluated for prediction performance and accuracy using receiver operating characteristic(ROC)curves,calibration curve and decision curve analyses.Results For clinical data,only the difference in gender between two groups had statistical significance(P<0.05).The spectral CT parameters(IC,NIC and Eff-Z)in the arterial and venous phases of PD-L1 positive group were all greater than those of PD-L1 negative group,with statistically significant differences(P<0.05).Multivariate Logistic regression analysis identified gender(P=0.024),venous-phase Eff-Z(P=0.002),and venous-phase IC(P=0.003)as independent predictive factors for PD-L1 expression.The nomogram prediction model constructed with these independent predictors had an area under curve of 0.80,a sensitivity of 88.00%,and a specificity of 59.00%.The calibration curve showed that the predicted values had a high consistency with the actual values.The decision curve revealed that when the high-risk threshold was between 0.10 and 0.83,the model could achieve the maximum net benefit.Conclusion The nomogram model constructed with spectral CT parameters and clinical data has certain value in predicting the expression level of PD-L1 in NSCLC.

Objective To investigate the preoperative prediction of the expression level of programmed cell death ligand 1(PD-L1)in non-small cell lung cancer(NSCLC)by a nomogram model constructed with clinical data,conventional CT signs and spectral CT parameters.Methods A retrospective analysis was conducted on 52 patients with pathologically confirmed NSCLC and undergoing preoperative spectral CT examination.The patients were categorized into positive and negative groups according to PD-L1 expression level,and their clinical data,conventional CT signs and spectral CT parameters were collected.Specifically,clinical data included gender,age,Ki-67 and tumor markers;conventional CT signs included tumor density,margins,calcification,spiculation,lobulation,pleural indentation and cavitation;and spectral CT parameters measured in the arterial and venous phases included effective atomic number(Eff-Z),iodine concentration(IC),water concentration(WC)and normalized iodine concentration(NIC).Intergroup differences were analyzed,and multivariate Logistic regression was used to identify independent predictors and establish the prediction model which was evaluated for prediction performance and accuracy using receiver operating characteristic(ROC)curves,calibration curve and decision curve analyses.Results For clinical data,only the difference in gender between two groups had statistical significance(P<0.05).The spectral CT parameters(IC,NIC and Eff-Z)in the arterial and venous phases of PD-L1 positive group were all greater than those of PD-L1 negative group,with statistically significant differences(P<0.05).Multivariate Logistic regression analysis identified gender(P=0.024),venous-phase Eff-Z(P=0.002),and venous-phase IC(P=0.003)as independent predictive factors for PD-L1 expression.The nomogram prediction model constructed with these independent predictors had an area under curve of 0.80,a sensitivity of 88.00%,and a specificity of 59.00%.The calibration curve showed that the predicted values had a high consistency with the actual values.The decision curve revealed that when the high-risk threshold was between 0.10 and 0.83,the model could achieve the maximum net benefit.Conclusion The nomogram model constructed with spectral CT parameters and clinical data has certain value in predicting the expression level of PD-L1 in NSCLC.

Objective:To investigate the predictive value of preoperative 18F-FDG PET/CT imaging for postoperative recurrence and metastasis in patients with stage Ⅰ solid and subsolid non-small cell lung cancer (NSCLC). Methods:This retrospective analysis included 139 patients (71 males, 68 females; age (62.1±9.0) years) with ⅠA1-ⅠB stage solid and subsolid NSCLC who underwent surgery and preoperative 18F-FDG PET/CT imaging at the Fourth Hospital of Hebei Medical University from December 2020 to December 2022. Patients were randomly divided into a training group and a validation group in a ratio of 7∶3, and SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG), clinical data, and disease-free survival (DFS) were collected. ROC curves were generated for the training group to determine the optimal cut-off values of SUV max, MTV, and TLG for predicting recurrence and metastasis. The Cox proportional hazards regression model was used to identify factors predicting DFS and to establish a prediction model, which was then validated in the validation group. The prognostic efficacy of the model was evaluated by using the concordance index (C-index). Results:Of 139 patients, 97 were in the training group and 42 were in the validation group, with 23 experienced recurrences during the follow-up period, including 18 in the training group and 5 in the validation group. The optimal cut-off values of SUV max, MTV and TLG for predicting tumor recurrence and metastasis in the training group were 5.85, 5.55cm 3, and 12.55g, respectively. Univariate analysis showed that SUV max (hazard ratio ( HR)=4.83, 95% CI: 1.81-12.89, P=0.002), MTV ( HR=6.90, 95% CI: 2.27-20.98, P<0.001), and TLG ( HR=5.77, 95% CI: 1.90-17.57, P=0.002) were predictive factors for postoperative recurrence and metastasis, while multivariate analysis identified MTV ( HR=4.67, 95% CI: 1.42-15.36, P=0.011) as an independent predictive factor. The prognostic C-index (95% CI) of models in training group and validation group were 0.814(0.745-0.882) and 0.810(0.624-0.995). Conclusions:Preoperative 18F-FDG PET/CT imaging has significant predictive value for postoperative recurrence and metastasis risk in patients with stage Ⅰ solid and subsolid NSCLC. MTV can be considered as an independent prognostic factor for preoperative recurrence and metastasis.

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions. As G protein-coupled receptors (GPCRs) are widely distributed throughout the body, including the pain transmission pathway and descending inhibition pathway, the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining momentum. Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects. This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain, and discuss the potential benefits and adverse factors of this treatment. We will also concentrate on the development of biased agonists of GPCRs, and based on important examples of biased agonist development in recent years, we will describe universal strategies for designing structure-based biased agonists. It is foreseeable that, with the continuous improvement of GPCRs allosteric modulation and biased agonist theory, effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

Professor Lau Wanyee, a member of the Chinese Academy of Sciences and a pro-fessor at the Chinese University of Hong Kong, actively advocates conducting clinical researches through "planting fruit trees" and "growing orchards", aiming to cultivate a team of dual-skilled talents in clinical practice and research, effectively improve the scientific and technological level of clinical medicine in China, make voice heard in the international medical science field, and better serve human health. He organized a clinical research training course in scholars′ forum for Hepatobiliary Young Expert Working Group of Chinese College of Surgeons. Throughout three sessions of the training course, a distinct theme was focused on how to enhance the level of clinical research in China and make voice heard by the international scholars. A group of multi-dimensional experts were gathered, including experts from surgery, methodology, and management, as well as both renowned experts and young talents. A lively teaching model was adopted, combining guided presentations with interactive discussion and debate sessions. A clean and upright academic spirit was strongly advocated, in which international rules were adopted to conduct in-depth analysis and sharp criticism of seven proposed clinical research projects and four published papers with high international influence to find quarrel in a straw. This clinical research training course provides a new model of guidance for young physicians in conducting clinical research. As a result, all attendees felt deeply educated and benefited greatly from the training session. This training activity not only laid a solid foundation for the development of scientization, standardization, and internationali-zation of clinical research in digestive surgery in China, but also demonstrated a correct path for cultivating a group of young and middle-aged clinical medical scientists with scientific spirit.

Objective:To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method:Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 μmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 μmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 μmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result:Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 μmol/L (IQR: 1846.09 μmol/L). The median IC50 for lobaplatin was 85.04 μmol/L (IQR: 305.01 μmol/L).The difference between the two groups was not statistically significant ( Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%?47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%?92.3%): this difference is statistically significant ( t=?15.282, P<0.001). Conclusion:The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

Objective:To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method:Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 μmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 μmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 μmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result:Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 μmol/L (IQR: 1846.09 μmol/L). The median IC50 for lobaplatin was 85.04 μmol/L (IQR: 305.01 μmol/L).The difference between the two groups was not statistically significant ( Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%?47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%?92.3%): this difference is statistically significant ( t=?15.282, P<0.001). Conclusion:The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

Objective:To investigate the factors related to hypothyroidism induced by programmed death(PD)-1 treatment in elderly patients with cancer.Methods:A total of 193 older patients(≥60 years old)with advanced solid tumors who received PD-1 treatment between January 2018 and January 2021 at the Department of Oncology of Xiangyang Central Hospital were included in this study.The patients were divided into two groups based on whether they were diagnosed with hypothyroidism after PD-1 treatment: the hypothyroidism group(36 cases)and the non-hypothyroidism group(157 cases).The clinical data of both groups, including age, gender, Eastern Cooperative Oncology Group performance status(ECOG PS), PD-1 inhibitors, thyroid function, and thyroid antibody, were compared to analyze the risk factors associated with hypothyroidism.Results:Among the 193 patients, 36(18.7%)were diagnosed with hypothyroidism.The study found no significant differences between the two groups in terms of age, gender, ECOG PS, tumor type, and PD-1 type(all P>0.05).However, significant differences were observed in the baseline levels of thyroid stimulating hormone(TSH)and thyroid antibody subgroups(both P<0.05).The results of multivariate Logistic regression analysis revealed that the presence of baseline anti-thyroid peroxidase antibody(TPOAb)( OR=20.256, 95% CI: 5.709-71.868, P<0.001), the presence of both baseline thyroglobulin antibody(TGAb)and TPOAb( OR=5.853, 95% CI: 1.475-23.227, P=0.012), and an increase in baseline TSH levels( OR=3.065, 95% CI: 1.049-8.959, P=0.041)were identified as risk factors for hypothyroidism induced by PD-1 treatment.On the other hand, there was no significant association between the presence of baseline TGAb and the occurrence of hypothyroidism( OR=1.373, 95% CI: 0.353-5.341, P=0.648). Conclusions:The incidence rate of hypothyroidism induced by PD-1 inhibitors is high among elderly patients with cancer.Additionally, the risk of hypothyroidism is higher in patients with elevated baseline TSH and positive TPOAb.Therefore, it is crucial to remain vigilant for the occurrence of hypothyroidism during PD-1 treatment.Timely diagnosis and treatment of hypothyroidism are necessary to minimize the incidence of adverse events.

Objective:To compare the predictive values of response evaluation criteria in lymphoma (RECIL)2017 and Lugano classification for the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) at the end of treatment.Methods:A total of 107 patients (50 males, 57 females, age (49.3±17.4) years) with DLBCL who underwent PET/CT at the end of chemotherapy in the Fourth Hospital of Hebei Medical University between February 2014 and December 2021 were analyzed retrospectively. The RECIL2017 and Lugano classification were used to evaluate the response. Kaplan-Meier survival analysis was used to evaluate progression-free survival (PFS) and overall survival (OS). The Kappa test was used to evaluate the consistency of the two criteria after chemotherapy, and ROC curve (Delong test)was used to compare the predictive values of the two criteria for PFS and OS. Results:The median follow-up time was 47.5(33.4, 57.5) months. Kaplan-Meier analysis showed that the 5-year PFS rates (74.5%(35/47), 71.4%(15/21), 57.1%(12/21), 4/18; χ2=38.85, P<0.001) and OS rates (89.4%(42/47), 81.0%(17/21), 61.9%(13/21), 7/18; χ2=29.52, P<0.001) in complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR) and progressive metabolic disease (PMD) groups evaluated by Lugano classification were statistically different, as well as those in complete response (CR), partial response (PR), minor response (MR), stable disease (SD) and progressive disease (PD) groups evaluated by the RECIL2017 (5-year PFS rates: 76.9%(40/52), 8/12, 6/11, 6/12, 30.0%(6/20), χ2=29.05, P<0.001; 5-year OS rates: 90.4%(47/52), 8/12, 6/11, 9/12, 45.0%(9/20), χ2=23.63, P<0.001). The RECIL2017 and Lugano classification had good consistency in the efficacy evaluation of DLBCL patients at the end of chemotherapy (70.1%(75/107); Kappa=0.57, P<0.001). The AUCs of Lugano classification for predicting PFS and OS were 0.730 (95% CI: 0.625-0.834, P<0.001) and 0.908 (95% CI: 0.845-0.970, P<0.001) respectively, and those of RECIL2017 were 0.717 (95% CI: 0.612-0.822, P<0.001) and 0.880 (95% CI: 0.812-0.949, P<0.001). The AUCs of the Lugano classification for PFS and OS were slightly higher than those of RECIL2017, without significant differences ( z values: 0.44, 1.09, both P>0.05) . Conclusion:Both RECIL2017 and Lugano classification can evaluate the prognosis of patients with DLBCL at the end of treatment, and Lugano classification is more accurate.