Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology， molecular docking， and in vitro cell experiments. MethodsIn this study， the canonical SMILES of magnoflorine was obtained from the PubChem database， and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database， while the disease targets of colon cancer were obtained from the DisGeNET， GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken， and a protein-protein interaction （PPI） network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology （GO） and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally， cellular experiments including CCK-8 assays， EdU experiments， cell scratch assays， and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 （STAT3） in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.

OBJECTIVE To establish an ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the simultaneous determination of the contents of six Aconitum alkaloids in Compound chondroitin sulfate tablets， and to perform quality evaluation of samples from different batches， thereby providing a reference for the quality control of this preparation.METHODS Chromatographic separation was performed on an Agilent SB-C 18 column using gradient elution with 0.2% formic acid （adjusted to pH 7.5 with ammonia） and acetonitrile as the mobile phases. The flow rate was 0.3 mL/min， the column temperature was 35 ℃， and the injection volume was 1 μL. Mass spectrometric analysis was performed using an AJS ESI + ion source in multiple reaction monitoring mode， with quantification by the external standard method. Method validation was performed. The established UPLC-MS/MS method was applied to determine the contents of the six Aconitum alkaloids in 64 batches of samples from three manufacturers， including three diester-type alkaloids （aconitine， hypaconitine， and mesaconitine） and three monoester-type alkaloids （benzoylaconine， benzoylhypaconine， and benzoylmesaconine）. Descriptive statistics， the Kruskal-Wallis H test， principal component analysis （PCA）， and Spearman’s rank correlation analysis were used to evaluate the content distribution of Aconitum alkaloids， differences among samples from different manufacturers， and correlations among the components.RESULTS Good linearity was observed for the six Aconitum alkaloids over their respective concentration ranges， with correlation coefficients （all r ＞0.99）. The relative standard deviations （RSDs） for precision， repeatability， and stability were all less than 5%. The limits of detection and quantification were no higher than 0.003 ng/mL and 0.01 ng/mL， respectively. The mean recoveries ranged from 96.43% to 102.30%， with RSDs ranging from 0.35% to 4.92%. Among the 64 batches of samples， the total content of monoester-type alkaloids （mean value of 0.034 9 mg/tablet） was markedly higher than that of diester-type alkaloids （mean value of 0.002 2 mg/tablet）. Benzoylmesaconine showed the highest content， with a mean value of 0.031 0 mg/tablet， whereas the other five components were present at relatively low levels and showed considerable inter-batch variation. No statistically significant differences were observed in the contents of the six components among samples from different manufacturers （ P ＞0.05）. PCA showed no obvious clustering trend， and significant correlations were observed among some components （ P ＜0.05）.CONCLUSIONS The established UPLC-MS/MS method enables the rapid and accurate simultaneous determination of the above-mentioned six Aconitum alkaloids in Compound chondroitin sulfate tablets. The quality evaluation of multiple batches of samples provides a reference for the quality control of this preparation.

[Purpose]To analyze global epidemic status of colorectal cancer and explore the rela-tionship between the human development index(HDI)and the burden of colorectal cancer.[Methods]Based on the GLOBOCAN 2022 estimation data,the disease burden of colorectal can-cer in different regions,countries,and levels of HDI were analyzed.Spearman's rank test was used to explore the correlation between HDI and colorectal cancer disease burden.[Results]The estimated global incidence of colorectal cancer in 2022 was 1 926 425 cases(1 069 446 for male and 856 979 for female),with a age-standardized incidence rate of 18.4/105(21.9/105 for male and 15.2/105 for female),and cumulative risk of incidence of 2.10％(2.60％for male and 1.70％for female);the estimated number of deaths was 904 019(499 775 for male and 404 244 for fe-male),with a age-standardized mortality rate of 8.1/105(9.9/105 for male and 6.5/105 for female)and cumulative risk of death of 0.84％(1.00％for male and 0.65％for female).1-crude mortality rate/crude incidence rate(1-M/I)was 0.53(0.53 for male and 0.53 for female).Large disparities were in the disease burden of colorectal cancer between different regions and countries.After grouped by HDI,we found that the age-standardized incidence rates in very high,high,median,and low HDI regions were 28.6/105,18.1/105,6.7/105,and 6.4/105,and the standardized mortality rates were 10.5/105,8.3/105,3.9/105,and 4.5/105,with 1-M/I of 0.57,0.52,0.43 and 0.30,respec-tively;and the incidence and mortality rates were increasing with age.Spearman's correlation analysis showed a strong positive correlation between HDI and colorectal cancer in age-standardized incidence(r=0.84),age-standardized mortality(r=0.71)and 1-M/I(r=0.82)(all P＜0.001).[Con-clusion]The global burden of colorectal cancer remains high.There are disparities in the disease burden among countries and regions,which is positively correlated with their HDI levels,indicating that the colorectal cancer prevention and treatment strategies should be developed based on the conditions of each regions and countries accordingly.

[Purpose]To analyze the incidence trend and age,period,cohort effects of brain and other central nervous system tumors(brain tumor)in Qidong City of Jiangsu Province from 1972 to 2021.[Methods]The incidence data of brain tumor from 1972 to 2021 were collected from the Qidong cancer registry database.The crude incidence rate(CR),age-standardized rate by Chi-nese standard population(ASRC),age-standardized rate by world standard population(ASRW)and average annual percentage change(AAPC)were calculated.The age-period-cohort(APC)model was used to analyze the age,period,and cohort effects of brain tumor incidence in Qidong City from 1972 to 2021.[Results]A total of 2 801 cases of brain tumor occurred in Qidong City from 1972 to 2021,including 1 475 male cases and 1 326 female cases.From 1972-1976 to 2017-2021,the CR increased from 1.81/10 5 to 9.28/10 5,the ASRC increased from 2.07/10 5 to 4.96/10 5,and ASRW increased from 2.00/105 to 4.98/105.From 1972 to 2021 the AAPC of CR,ASRC and ASRW were 3.97％(3.53％for male and 4.37％for female),2.02％(1.66％for male and 2.24％for female)and 2.06％(1.63％for male and 2.24％for female)(all P＜0.001).The Wald's Chi-square test of the APC model showed that there were significant differences in the trends of age,period and birth cohort effect of brain tumor risk(all P＜0.05).The age effect showed that the incidence of brain tumor increased with age,starting from the age group of 45～49 years old and reaching a peak of 25.84/10 5 in age group of 75～79 years old(95％CI:21.17/10 5～31.53/10 5).The period ef-fect showed that the risk of recent period was higher than that in the early period using 1992-1996 period as the reference,reaching the highest in 2012-2016(RR=1.64,95％CI:1.38～1.95).The birth cohort effect showed that the highest risk was in 2017-2021 births cohort(RR=11.17,95％CI:4.26～29.26)using 1952-1956 birth cohort as the reference.[Conclusion]The incidence of brain tumor in Qidong City has been rising;and age,period and cohort are the main influencing factors,suggesting that the middle-aged and elderly population should be the focus of brain tumor prevention and control.

Objective To analyse medication patterns for treating menstrual disorders with disharmony between the Chong and Ren pattern based on data mining.Methods Medical records from the gynecological outpatient department of Wenzhou TCM Hospital of Zhejiang Chinese Medical University from October 2023 to March 2024 were collected.A database was established based on Traditional Chinese Medicine Inheritance Computer System(V3.0),and data mining methods such as frequency statistics,association rule analysis and cluster analysis were used to analyze the medication patterns of traditional Chinese medicine in the treatment of menstrual disorders with disharmony between the Chong and Ren pattern.Results A total of 9003 effective prescriptions were collected,involving 410 Chinese medicinal herbs.The top five herbs by frequency were Danggui,Tusizi,Cuxiangfu,Xuduan,and Danshen.Tonic medicines,circulate blood and transform stasis medicines and interior heat-clearing medicines were used more frequently.The four qi were mainly warm and cold,the five lavours were mainly bitter and sweet,and the channel were mainly liver and spleen channel.By association analysis,a combination of drugs with Tusizi,Gouqizi,Danggui,Xuduan,Cuxiangfu were obtained.After cluster analysis,five groups of effective class squares were obtained.Conclusion Treatment of menstrual disorders with disharmony between the Chong and Ren pattern is used to tonic medicines,circulate blood and transform stasis medicines and interior heat-clearing medicines,pay attention to the balance of liver,spleen,kidney.The prescribing strategy considers both superficial and underlying conditions,employs a gradual rather than abrupt approach,integrates both cold and warm remedies,and ensures mutual reinforcement and restriction among the treatments.

Objective:To analyze the efficacy of delineating the clinical target volume (CTV) following the trajectory of trigeminal nerve branches and elective neck irradiation (ENI) in postoperative intensity-modulated radiotherapy (IMRT) for adenoid cystic carcinoma of head and neck (ACCHN).Methods:In this study, the data of ACCHN patients without distal metastasis who received postoperative radiotherapy after radical surgery at the Ninth People's Hospital of Shanghai Jiaotong University School of Medicine from January 2016 to December 2022 were retrospectively analyzed. Postoperative radiotherapy target zone and intensity-modulated radiotherapy plan for ACCHN were formulated according to the site of primary focus, whether nerve invasion and pathological staging. Kaplan-Meier method was applied to perform survival analysis, while assessing the tumor local control rate and locoregional recurrence pattern under this target zone outlining principle.Results:A total of 309 ACCHN patients were included. With a median follow-up of 49 months, the 5-year local control rate was 93.2%, the 5-year overall survival rate, locoregional recurrence-free survival rate, and distant metastasis-free survival rate were 90.8%, 90.6%, 66.3%, respectively. Twenty-three patients developed locoregional recurrence, including 14 with primary tumor recurrence alone, 5 with regional lymph node recurrence alone, and 4 with both primary and regional lymph node recurrence. Among the patients with primary tumor recurrence, 11 had recurrence related to the trigeminal nerve branches,and 7 had recurrence in the tumor bed or surgical bed region, with no out-of-field recurrence. Among the 9 patients with lymph node recurrence, none had undergone neck dissection.Conclusions:Delineating the CTV following the trigeminal nerve branches in postoperative radiotherapy for ACCHN achieves excellent local control. Elective neck irradiation avoids irradiation of the entire neck lymphatic drainage area with a low regional recurrence rate.

Objective:To evaluate the impact of surgical margin status and pathological subtypes on the prognosis of patients with adenoid cystic carcinoma of the head and neck (ACCHN) who underwent postoperative radiotherapy.Methods:A retrospective analysis was conducted on 309 patients with initially treated, non-metastatic ACCHN who completed postoperative radiotherapy at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. All patients underwent curative (non-palliative) surgery followed by postoperative radiotherapy, with a median dose of 66 Gy (range: 54-70 Gy). The Kaplan-Meier method was used to compare 5-year local recurrence-free survival (LRFS) between R0 (negative margin) and non-R0 resections in patients with initially resectable (T 1-T 4a stage) and initially unresectable (T 4b stage) disease. Univariate and multivariate Cox proportional hazards models were employed to analyze risk factors for local recurrence, with a focus on surgical margin status and pathological subtypes. Results:The median follow-up was 48 months. Of the 309 patients included in the study, 133 were males and 176 were females, with a median age of 51 years (range: 18-77 years). Primary tumors were located in the major salivary glands in 135 cases (including 42 in the parotid gland, 65 in the submandibular gland, and 28 in the sublingual gland) and in the minor salivary glands in 174 cases. The 5-year overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and progression-free survival rates were 91.5%, 90.8%, 66.1%, and 63.9%, respectively. Non-R0 resection was achieved in 177 patients (57.3%). Among initially resectable patients ( n=253), the non-R0 resection rate was 49.0% ( n=124), with only 6 cases (2.4%) experiencing local recurrence (all non-R0 resections). In initially unresectable patients ( n=56), the non-R0 resection rate was as high as 95% ( n=53), with 13 cases (23%) experiencing local recurrence (2 cases in non-R0 resection and 1 case in R0 resection). For initially resectable patients, non-R0 resection significantly reduced the 5-year LRFS rate to 95.2%, compared to 100% in R0 resection patients ( P=0.014). However, multivariate analysis revealed that the solid pathological subtype was an independent risk factor for 5-year LRFS ( HR=7.40, 95% CI: 2.81-19.52, P<0.001), while the surgical margin status was not an independent factor. Conclusions:The combined strategy of surgery and postoperative radiotherapy provides high local control rates for ACCHN patients. Achieving R0 resection is crucial for initially resectable patients, while a comprehensive treatment strategy involving surgery and postoperative radiotherapy remains essential for initially unresectable patients. The solid pathological subtype is the most significant risk factor for local recurrence.

Objective:To analyze pancreatic cancer incidence and mortality data in China and worldwide and to provide data for pancreatic cancer prevention and control efforts.Methods:Data of pancreatic cancer incidence and mortality rates, along with historical and predictive data, were obtained from the GLOBOCAN 2022 database. Epidemiological characteristics of pancreatic cancer was analyzed by region, sex, age and Human Development Index (HDI). Spearman's correlation coefficient test was used to assess the relationship between HDI and age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR).Results:In 2022, the global number of new cases and deaths of pancreatic cancer will be 511 thousand and 467 thousand, respectively, with an ASIR and ASMR of 4.7/10 5 and 4.2/10 5, respectively. North America and Europe had the highest pancreatic cancer incidence and mortality rates of 8.5/10 5 and 7.3/10 5, respectively. Global ASIR and ASMR in men were both 1.4 times higher than those in women. HDI levels were positively correlated with ASIR ( r=0.79, P＜0.001) and ASMR ( r=0.78, P＜0.001) of pancreatic cancer in all regions. The number of pancreatic cancer cases and deaths in China were 119 thousand and 106 thousand, respectively, while the ASIR and ASMR of pancreatic cancer were 4.4/10 5 and 3.9/10 5, respectively. Both ASIR and ASMR in men were both 1.5 times higher than those in women in China. The number of pancreatic cancer incidence and death cases in China in 2050 is predicted to be 216 thousand and 204 thousand cases, with an increase of 81.5% and 92.5% compared with 2022, respectively. Conclusions:The disease burden of pancreatic cancer varies significantly among different regions, genders and ages. Pancreatic cancer incidence and mortality are positively correlated with HDI. The incidence and mortality rates of pancreatic cancer in China are close to the global average, but the number of new cases and deaths is high. Prevention and control should be strengthened to improve the survival of pancreatic cancer patients.

Objective:To analyze the trend of ovarian cancer incidence in Qidong City from 1972 to 2021 and evaluate the age, period, and cohort effect.Methods:The ovarian cancer incidence data from 1972 to 2021 were extracted from the Qidong Cancer Registry Database, the crude incidence rate (CR), age standardized rate by Chinese population (ASR-C), age standardized rate by world population (ASR-W), and average annual percent change (AAPC) were calculated. The age-period-cohort model was used to analyze the age, period, and birth cohort effects of the ovarian cancer incidence in Qidong from 1972 to 2021.Results:From 1972 to 2021, a total of 1 007 cases of ovarian cancer occurred in Qidong. The AAPC values of CR, ASR-C, and ASR-W were 7.02% , 5.17%, and 5.12% , respectively (all P＜0.001). The time trends showed that, the AAPC values of the age groups of 0-34, 35-44, 45-54, 55-64, 65-74, and over 75 years old were 4.10%, 4.74%, 6.02%, 4.86%, 4.23%, and 5.18%, respectively (all P＜0.05). The age effect showed that the incidence rate of ovarian cancer increased obviously from the 45-49 year-old group, reaching a peak of 20.67/100 000 in the 75-79 year-old group. Compared with the 1992-1996 group, the period of 2002-2021 had significant effects on the incidence rise of ovarian cancer (all P＜0.05), and the incidence rate ratio ( RR) increased with the period: in 2017-2021 the RR was 3.86 (95% CI: 2.72-5.47). Using births from 1952 to 1956 as the reference group, the RR increased slowly from 0.12 (95% CI: 0.02-0.91) in 1892-1896, and peaked in 2007-2011 with an RR of 18.05 (95% CI: 3.51-92.87). The birth cohorts in 1967-2011 had significant effects on the incidence rise of ovarian cancer (all P＜0.05). The Waldχ 2 test of the age-period-cohort model showed that there were significant differences in the age, period, and birth cohort effects (all P＜0.001). Conclusions:The incidence of ovarian cancer in Qidong was on the rise. Age, period, and cohort were the main factors affecting the incidence of ovarian cancer. The middle-aged and elderly women were the focus of ovarian cancer prevention and control.