Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective:To evaluate the safety and feasibility of neoadjuvant chemotherapy (NACT) combined with radical surgery for elderly patients with locally advanced gastric cancer (LAGC).Methods:One hundred and fourty eight patients with LAGC after NACT and gastrectomy between 2012 and 2020 were retrospectively reviewed. They were divided into two groups: (1) <65 years old (111 cases) and (2) ≥65 years old (37 cases) and their clinicopathological and prognostic data were compared.Results:There was no significant difference between the two groups in the incidence of hematological complications such as anemia ( χ2=0.235, P=0.628), leukopenia ( χ2=0.613, P=0.434), neutropenia ( χ2=0.011, P=0.918) and thrombocytopenia ( χ2=0.253, P=0.615) and non-hematological complications such as nausea ( χ2=0.092, P=0.762), vomiting ( χ2=0.166, P=0.683), diarrhea ( χ2=0.015, P=0.902) and mucositis ( χ2=0.199, P=0.766) due to NACT. There were no statistical differences between the older patients and the younger in operation duration ( t=0.270, P=0.604), intraoperative bleeding ( t=1.140, P=0.250) and R 0 resection rate ( χ2=0.105, P=0.750). The incidence of postoperative complications was 25.2% and 37.8% in the younger patients and the olders ( χ2=2.172, P=0.141). Pleural effusion ( χ2=7.007, P=0.008) and pulmonary infection ( χ2=10.204, P=0.001) was significantly higher in the older patients than in the youngers. The 3-year progression-free survival rate ( t=0.494, P=0.482) and 3-year overall survival rate ( t=0.013, P=0.908) were comparable between the two groups. Conclusions:NACT combined with radical surgery is safe and effective in elderly patients with LAGC, except for higher perioperative pulmonary-related complications.

Objective:To evaluate the dosimetric effects of different aperture shape controller (ASC) parameters based on the Halcyon 3.0 accelerator in the hippocampal avoidance-whole brain radiotherapy (HA-WBRT) plans.Methods:This study enrolled 13 patients treated with WBRT using a Halcyon 3.0 accelerator at the Department of Radiotherapy of the Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. According to different aperture shape controller (ASC) parameters, the HA-WBRT plans were divided into six groups, namely non, very low, low, moderate, high, and very high ASC settings, marked by AO, AVL, AL, AM, AH, and AVH, respectively. This study presented a statistical evaluation of the effects of different ASC parameters on conformity index (CI), homogeneity index (HI), radiation doses to the hippocampus and other organs at risk, and the plans’ execution efficiency. Furthermore, using two dose verification tools, namely ArcCHECK and Portal Dosimetry, this study delivered a comprehensive analysis of the differences in beam delivery precision of the plans with different ASC parameters.Results:The six groups all met the requirements for clinical treatment. They had similar CI and HI values, with no statistically significant differences ( P > 0.05). The AVH group showed better protection effects on organs at risk. Compared to the control group, the AVL group showed lower Dmax of brainstems but higher Dmax of chiasma opticum ( F = 6.26, 8.04, P < 0.05). Compared to the control group, the AH group showed lower Dmax of eyeballs but higher Dmax of optic nerves ( F = 2.04, 1.37, P < 0.05). In contrast, the AVH group exhibited lower Dmax of brainstems, eyeballs, and lens than the control group ( F = 6.26, 2.04, 2.02, P < 0.05). No statistically significant differences were observed in dosimetric indices of other organs at risk ( P > 0.05). As verified using ArcCHECK and Portal Dosimetry, the γ passing rates of the six groups were over 98% at 2%/2 mm and 100% at 3%/3 mm. The overall γ passing rates verified using ArcCHECK were lower than those verified using Portal Dosimetry. The maximum difference in the monitor unit among the six groups was less than 15, and these groups did not show significant differences in terms of execution efficiency. Conclusions:The HA-WBRT plans based on the Halcyon 3.0 accelerator can meet the requirements for clinical treatment. Different ASC parameters can significantly optimize the dosimetric parameters. Among them, the AVH parameters can highly reduce the radiation dose to organs at risk. Furthermore, different ASC parameters show insignificant effects on beam delivery precision and plan execution efficiency, meeting the verification standards for clinical therapeutic doses.

OBJECTIVE To construct the quantitative evaluation system of regional clinical pharmacists’ professional ability， and provide reference for the evaluation of regional clinical pharmacists’ professional ability. METHODS Twenty-one experts from 18 hospitals in Chongqing were consulted to construct a professional ability index system for clinical pharmacists. TOPSIS model was used to calculate and obtain the expert authority index （EI）， and the weighted averaging method was used to construct the judgment matrix. Analytic hierarchy process （AHP） was used to calculate the weights of all indicators for establishing a quantitative evaluation system of regional clinical pharmacists’ professional ability according to the weights of each item. RESULTS The results of TOPSIS showed that the EI range was 0.010-0.100， and the relative authority of experts was distinguished and measured effectively. The results of AHP showed that the judgment matrix of the quantitative evaluation system met the requirements of consistency test （consistency test index CR＜0.1）. Finally， a quantitative evaluation system for regional clinical pharmacists’ professional ability was established， including 6 sub-objective items （basic ability， clinical practice ability， coordination and communication ability， publicity ability， scientific research and teaching ability， continuous improvement ability） and 25 index items （such as educational background， professional title， clinical pharmacy working years， daily theoretical skills assessment， information ability level， medication education， etc.）. CONCLUSIONS A quantitative evaluation system of regional clinical pharmacists’ professional ability has been established. Our study provides a theoretical reference for the quantitative evaluation and optimal management of regional clinical pharmacists.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. METHODS: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. RESULTS: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. CONCLUSION: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Brain Neoplasms/genetics*

Objective:To investigate the clinicopathological features and prognosis of patients with gastric gastrointestinal stromal tumor (GIST) combined with digestive tract cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 163 patients with gastric GIST who were admitted to the Union Hospital admitted to Tongji Medical College of Huazhong University of Science and Technology from January 2002 to December 2021 were collected. There were 606 males and 557 females, aged 59(range,20?94)years. Of the 1 163 patients, 129 cases with gastric GIST combined with other digestive tract cancer were divided into the combined group, and 1 034 cases with only gastric GIST were divided into the non-combined group. Observation indicators: (1) clinicopathological features of patients; (2) surgical situations and postoperative complications; (3) follow-up and survival of patients; (4) analysis of prognosis associated affecting factors. Follow-up was conducted using outpatient examination, telephone and online interview to detect survival of patients up to January 2022. The overall survival time was defined as the time from surgery to the last tine of follow-up or the outcome events, such as death of patient, loss of follow-up, etc. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Com-parison of ordinal data was conducted using the non-parameter Mann-Whitney U test. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and Log-Rank test was used to conduct survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Results:(1) Clinicopathological features of patients. Of the 129 patients in the combined group, there were 81 cases combined with gastric cancer, 39 cases combined with esophageal cancer, 8 cases combined with colon cancer and 1 case combined with rectal cancer. Gender (male, female), cases with age ≤60 years or>60 years, cases without or with clinical symp-toms before surgery, cases with tumor diameter of gastric GIST as<2 cm, 2?5 cm, 5?10 cm,>10 cm, cases with mitotic index as <5/50× high power field, 5?10/50× high power field, >10/50× high power field, cases with cell proliferation index of Ki-67 as ≤5% or >5%, cases classified as extremely low risk, low risk, medium risk and high risk of the modified national institutes of health (NIH) risk classification, cases with or without tumor necrosis of the gastric GIST, cases without or with adjuvant imatinib therapy, cases with the expression of DOG-1 detected by immunohistochemical staining as positive or negative, cases with the expression of CD34 as positive or negative were 92, 37, 30, 99, 9, 120, 114, 10, 3, 2, 126, 1, 2, 122, 2, 112, 8, 5, 4, 129, 0, 121, 8, 118, 3, 117, 12 in the combined group, versus 514, 520, 585, 449, 194, 840, 383, 360,201, 90, 799, 155, 80, 851, 143, 337, 308, 192, 197, 960, 74, 769, 265, 850, 80, 990, 44 in the non-combined group, showing significant differences in the above indicators between the two groups ( χ2=21.46, 51.11, 11.06, Z=?10.27, ?5.34, χ2=15.94, Z=?10.61, χ2=9.86, 24.10, 5.52, 6.37, P<0.05). Of the 1 163 patients, there were 12 cases of the combined group suspected diagnosed as gastric GIST before surgery and 1 case of the combined group dia-gnosed as gastric GIST by gastroscopy and pathological examination before surgery. The rest of 1 150 patients were diagnosed as gastric GIST by intraoperative exploration or postoperative pathological examination. (2) Surgical situations and postoperative complications. Of the 129 patients in the combined group, 72 cases underwent open surgery and 57 cases underwent laparoscopic or thoracoscopic surgery including 3 cases converted to open surgery. Of the 1 034 patients in the non-combined group,207 cases underwent endoscopic surgery, 371 cases underwent open surgery, and 456 cases underwent laparoscopic or thoracoscopic surgery including 8 cases converted to open surgery. Incidence of postoperative complications was 10.078%(13/129) in the combined group, versus 2.321%(24/1 034) in the non-combined group, showing a significant difference between the two groups ( χ2=22.40, P<0.05). (3) Follow-up and survival of patients. Of the 1 163 patients, 1 046 cases were followed up for 44(range, 1?220)months, with the postoperative 5-year overall survival rate as 87.2%. The postoperative 5-year overall survival rate was 51.2% in the combined group, versus 91.4% in the non-combined group, showing a significant difference between the two groups ( χ2=169.07, P<0.05). (4) Analysis of prognosis associated affecting factors. Results of univariate analysis showed that gender, age, tumor diameter of gastric GIST as 2?5 cm, 5?10 cm and >10 cm, combined with other digestive tract cancer, mitotic index as >10/50× high power field and tumor necrosis of the gastric GIST were related factors affecting the postoperative 5-year overall survival rate of patients with gastric GIST ( hazard ratio=2.16, 2.27, 0.46, 0.57, 1.75, 7.58, 2.70, 1.80, 95% confidence intervals as 1.52?3.07, 1.60?3.22, 0.29?0.71, 0.34?0.94, 1.11?2.77, 5.29?10.85, 1.67?4.38, 1.08?2.98, P<0.05). Results of multivariate analysis showed that gender, age, tumor diameter of gastric GIST, combined with other digestive tract cancer and mitotic index were independent factors affecting the post-operative 5-year overall survival rate of patients with gastric GIST ( hazard ratio=1.91, 1.82, 2.10, 7.11, 2.75, 95% confidence intervals as 1.33?2.75, 1.27?2.62, 1.14?3.87, 4.58?11.04, 1.50?5.03, P<0.05). Conclusions:The tumor diameter of gastric GIST is short in patients combined with other digestive tract cancer, and the risk grade of modified NIH risk classification is lower. Gender, age, tumor diameter of gastric GIST, combined with other digestive tract cancer and mitotic index are independent factors affecting the postoperative 5-year overall survival rate of patients with gastric GIST.

Objective : This experiment was carried out to study the effects of chronic inflammatory pain on the gut flora of mice by 16S rRNA high⁃throughput sequencing. Methods : Twelve specific pathogen free (SPF) C57BL/ 6J mice were randomly divided into CFA group and mock group , with 6 mice in each group. Chronic inflammatory pain model was established by intraplantar injection of CFA in the right posterior pelma of C57BL/6J mice. In the control group , normal saline was injected by intraplantar injection in the same position. Two weeks later, the mice were euthanized , and the feces in the colon were collected. The feces of two mice in the same group were mixed , detected and analyzed by 16S rRNA high⁃throughput sequencing technology. Results : Compared with mock group , the abundance and diversity of gut flora in CFA group decreased. The abundance of Firmicutes and TM7 increased at the phylum level , the abundance of Aerococcus , Lactobacillus and Desulfovibrio increased significantly at the fami ⁃ ly and genus level , while the abundance of Psychrobacter, Prevotella , Oscillospira and Bifidobacterium decreased significantly compared to mock group. In addition , many biomarkers were found from the level of the phylum to the genus. Conclusion The gut microflora structure , especially the dominant flora , has changed significantly in mice with chronic inflammatory pain , which can provide basis for the treatment of microecological imbalance caused by chronic inflammatory pain and the improvement of patients ′ negative emotions through“ gut brain axis”.

Objective:This study explored the association between antenatal calcium supplementation in the childbearing aged women and risk of small for gestational age infant (SGA) among singleton in Shaanxi province,China.Methods:Multi-stage random cluster sampling method was employed to collect information about pregnant women, who were pregnant and had definite outcomes, and their infants, from 30 districts (counties) in 2010 to 2013. Information was collected by face-to-face questionnaire survey. Generalized linear mixed models were employed after adjusting covariates. Dependent variable was whether single-birth neonate was SGA, and independent variable was calcium supplementation of childbearing aged women in different pregnant periods.Results:A total of 28 357 childbearing aged women was recruited in this study. The age of these women was (28.08±4.74) years old, of which, 79.28% were rural residents and 60.90% had calcium supplementation intake. There was a number of 12 810 female in singleton neonates. The neonatal birth weight and gestational age were (3.27±0.16) kg and (277.44±8.80) day, respectively. The prevalence of SGA was 11.35% in total, and 10.48% in mothers with maternal calcium supplementation and 12.70% in mothers without maternal calcium supplementation in whole antenatal period. There were statistically significant differences seen in antenatal calcium supplementation within the subgroups of maternal age (whether the mother was an advanced maternal woman), residential area, maternal occupation, maternal parity, maternal education level, and household incomes ( P<0.05). After adjusting these covariates, the risk of SGA among childbearing aged women with antenatal calcium supplementation showed 16% decreased risk ( OR=0.84, 95% CI: 0.77-0.92). Further analysis of the different antenatal periods showed that calcium supplementation during the second and third trimester had a statistically significant difference in reducing the risk of neonatal SGA ( P<0.05). Besides, subgroup analysis showed that there was a statistically significant difference between the perinatal calcium supplementation and the single-born neonates with SGA Significance ( P<0.05) in non-advanced women, those who had a low education level and moderate household economic status groups. Conclusion:The risk reduction of SGA among singleton neonates is related to calcium supplementation during antenatal period in Shaanxi province.

Leucine rich glioma inactivated 1 (LGI1) is a protein which is identified as the target involving in autoimmune encephalitis. Seizures and cognitive declines are two main symptoms of LGI1-antibody encephalitis. However, autonomic dysfunction symptoms are not prominent as seizures and cognitive defection and are easily overlooked by physicians. We reported a case with LGI1-antibody encephalitis whose onset symptoms were autonomic dysfunction including sweating, orthostatic hypotension. The features of this case was described in detail and the related literatures were reviewed in order to enhance the knowledge of the disease.