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 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.

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 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.

Humans ; Consensus ; Liver Neoplasms/therapy* ; China

Prostate cancer poses a serious threat to the health of men with an increasing incidence in China. In recent years, great progress has been made in surgical and pharmaceutical treatment, but there are few promising techniques for early diagnosis of prostate cancer or therapeutics for advanced prostate cancer. Engineered nanomaterials have emerged and shown great potential in early diagnosis, precisely targeted therapies and synergistic therapeutics for prostate cancer because of unique physicochemical properties, such as size on the nanoscale, large specific surface area, high drug loading efficiency, fluorescence excitation ability and photothermal/photodynamic effect. This review focused on the new diagnoses and treatment strategies in prostate cancer with engineered nanomaterials, by summarizing the advancement of engineered nanomaterials in improving the sensitivity of molecular biology and imaging diagnosis, targeted guidance in surgery, sensitization of radiotherapy and chemotherapy, and targeted drug delivery.

Background/Aims: Colorectal cancer (CRC) patients often exhibit peritoneal metastasis, which negatively impacts their prognosis. CD31 and D2-40 have recently been suggested to be predictors of breast cancer prognosis, but their role in colorectal peritoneal metastasis (CRPM) remains unknown. Methods: The expression profiles of CD31 and D2-40 were analyzed in CRC patients with or without CRPM and in CRC cell lines with increasing metastatic potential. Overexpression and short hairpin RNA knockdown assays were performed in CRC cells, and the effects of these alterations on epithelial-mesenchymal transition (EMT) in vitro, growth of xenograft tumors in vivo, and peritoneal metastasis potential in a mouse model of CRPM were examined. Results: The expressions of CD31 and D2-40 were upregulated in CRC tumor tissues and was elevated further in tumor tissues from patients with CRPM. CD31 and D2-40 expression levels exhibited increasing trends parallel to the EMT potential of CRC cells. CD31 and D2-40 are essential for CRC cell EMT in vitro as well as for xenograft tumor growth and peritoneal metastasis in vivo. Conclusions CD31 and D2-40 contribute to CRPM by promoting EMT and may serve as prognostic markers and therapeutic targets for CRC, particularly in patients with peritoneal metastasis.

Objective:To compare the effectivity and safety of ureteral stenting and percutaneous nephrostomy for patients with upper urinary calculi and sepsis.Methods:From June 2013 to June 2019, 429 patients with upper urinary calculi and urosepsis were accepted in the second hospital of Tianjin Medical University. According to surgical decompression, patients were divided into two groups, ureteral stenting (US, n=304) and percutaneous nephrostomy (PCN, n=125).121 patients were accompanied with septic shock in US group, 56 in PCN group. The effectivity of decompression was analyzed separately in patients with or without shock. For decompression, data included the success rate of decompression, the time of infection related parameters (temperature, blood WBC and CRP) returning to normal and the complications (progress of infection within 30min after decompression, perforation of ureter or pelvis). When urosepsis was cured, ureteroscopic lithotripsy was followed for all patients. The operation time, the stone free rate, the rate of using RIRS and the complications were compared.Results:For patients without septic shock, the success rate of decompression in PCN was higher (68/69)than that of US(165/183)( P =0.025); there was no significant difference in hospital stay for infection control and the time of infection related parameters (temperature, blood WBC and CRP) returning to normal ( P>0.05). The rate of infection progress within 30min in US(25/183) was higher than PCN(3/69)( P=0.036). When ureteroscopic lithotripsy was mentioned, the operation time in US(38.5±6.8 min) was longer than PCN(32.8±4.5 min)( P=0.000), the stone free rate and the rate of using RIRS were lower in PCN( P=0.044, P=0.0002). For patients with septic shock, the success rate of decompression in PCN was higher (55/56)than that of US(106/121)( P=0.022). The rate of infection progress within 30min after decompression was still higher in US ( P=0.048), the time of infection related parameters (temperature, blood WBC and CRP) returning to normal was shorter in PCN ( P=0.000, P=0.003, P=0.000). For lithotripsy, the operation time was longer in US ( P=0.017), the stone free rate and the rate of using RIRS were lower in PCN ( P=0.024, P=0.005). Conclusions:For patients with upper urinary calculi and urosepsis, both ureteral stenting and percutaneous nephrostomy can drainage the pelvis effectively. PCN provides quick recovery, especially when septic shock is involved. For the following ureteroscopic lithotripsy, PCN contributes to less operation time and higher stone free rate, reduces the use of flexible ureteroscope.