Objective:To explore the efficacy and safety of ultrasound-guided radiofrequency ablation for liver metastasis combined with laparoscopic resection of colorectal cancer in the treatment of colorectal cancer liver metastasis (CRLM).Methods:A retrospective cohort study was conducted. Sixty-five CRLM patients who were admitted to Shanxi Province Cancer Hospital from July 2018 to July 2020 were collected and divided into two groups based on different surgical methods: the ultrasound-guided radiofrequency ablation treatment for liver metastasis combined with laparoscopic colorectal cancer resection group (study group) and the total laparoscopic surgery group (control group), with 26 and 39 cases, respectively. The postoperative hospitalization time, surgical cost, intraoperative blood loss, postoperative anal exhaust or defecation time, postoperative feeding time, incidence of postoperative complications, postoperative recurrence and survival status were compared between the two groups of patients.Results:There was no statistically significant difference in age, gender, type of colorectal cancer, number of liver metastasis, and maximum diameter of liver metastasis between the two groups of patients (all P > 0.05). The study group and the control group showed statistically significant differences in postoperative hospitalization time [(5.4±2.2) d vs. (7.0±2.5) d], surgical costs [(4.7±0.8) ten thousand yuan vs. (3.9±0.6) ten thousand yuan], intraoperative blood loss [(104±11) ml vs. (187±20) ml], postoperative anal exhaust or defecation time [(2.2±1.5) d vs. (3.5±1.3) d], and postoperative feeding time [(2.4±1.6) d vs. (3.8±1.2) d] ( t values were 2.82, 4.63, 21.95, 3.57, and 3.65, respectively, all P < 0.01). There was no statistically significant difference in the incidence of subphrenic infection, incision infection, bile leakage, postoperative wound bleeding, liver failure, postoperative 3-year recurrence rate, and postoperative 1-, 2- and 3-year survival rates between the study group and the control group (all P > 0.05). Conclusions:The effect of ultrasound-guided radiofrequency ablation for liver metastasis combined with laparoscopic resection of colorectal cancer for CRLM is comparable to that of total laparoscopic surgery, and the hospitalization time, exhaust or defecation time and feeding time are shortened, the intraoperative bleeding is less, and the surgical complications are not increased.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Objective:To explore the efficacy and safety of ultrasound-guided radiofrequency ablation for liver metastasis combined with laparoscopic resection of colorectal cancer in the treatment of colorectal cancer liver metastasis (CRLM).Methods:A retrospective cohort study was conducted. Sixty-five CRLM patients who were admitted to Shanxi Province Cancer Hospital from July 2018 to July 2020 were collected and divided into two groups based on different surgical methods: the ultrasound-guided radiofrequency ablation treatment for liver metastasis combined with laparoscopic colorectal cancer resection group (study group) and the total laparoscopic surgery group (control group), with 26 and 39 cases, respectively. The postoperative hospitalization time, surgical cost, intraoperative blood loss, postoperative anal exhaust or defecation time, postoperative feeding time, incidence of postoperative complications, postoperative recurrence and survival status were compared between the two groups of patients.Results:There was no statistically significant difference in age, gender, type of colorectal cancer, number of liver metastasis, and maximum diameter of liver metastasis between the two groups of patients (all P > 0.05). The study group and the control group showed statistically significant differences in postoperative hospitalization time [(5.4±2.2) d vs. (7.0±2.5) d], surgical costs [(4.7±0.8) ten thousand yuan vs. (3.9±0.6) ten thousand yuan], intraoperative blood loss [(104±11) ml vs. (187±20) ml], postoperative anal exhaust or defecation time [(2.2±1.5) d vs. (3.5±1.3) d], and postoperative feeding time [(2.4±1.6) d vs. (3.8±1.2) d] ( t values were 2.82, 4.63, 21.95, 3.57, and 3.65, respectively, all P < 0.01). There was no statistically significant difference in the incidence of subphrenic infection, incision infection, bile leakage, postoperative wound bleeding, liver failure, postoperative 3-year recurrence rate, and postoperative 1-, 2- and 3-year survival rates between the study group and the control group (all P > 0.05). Conclusions:The effect of ultrasound-guided radiofrequency ablation for liver metastasis combined with laparoscopic resection of colorectal cancer for CRLM is comparable to that of total laparoscopic surgery, and the hospitalization time, exhaust or defecation time and feeding time are shortened, the intraoperative bleeding is less, and the surgical complications are not increased.

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

Objective:To describe the characteristics and medical seeking behaviors of female infertility patients in assisted reproductive institutions in China overall and geographical regions, and compare the differences among the eastern, the middle and the western regions.Methods:This study used the data from Unit 6-Analysis on the matching status of reproductive health and health care services among reproductive age population and demonstration and promotion study of diagnosis and treatment in National Key R&D Program "Reproductive Health and Major Birth Defects Prevention and Control Study" participated by the Assisted Reproductive Technology Management Department of Maternal and Child Health Care Center, Chinese Center for Disease Control and Prevention. One assisted reproductive institution with more than 1 000 and less than 1 000 oocyte retrieval cycles by in vitro fertilization techniques in 2018 was selected from 8 provincial capital cities in different regions of eastern and western China, and the questionnaire data of infertile female patients aged 20-49 years who first visited the outpatient clinics of 16 institutions were analyzed. The patient's age, degree of culture, annual personal income, try-to-conceived time, and one-way transportation time were analyzed using the frequency description, χ 2 test, Kruskal-Wallis H test and other methods. Results:A total of 3 673 female patients were finally included as study subjects. The patient's age was (31.0±4.6) years old, and 59.0% (2 156/3 660) was an undergraduate/college degree or above, with a median pregnancy test duration of 2.0 (1.3, 3.5) years. In terms of demographic characteristics, the proportion of patients over 35 years old in the eastern and western regions was greater in small institutions, 22.8% (216/948) and 26.4% (148/561), respectively. The proportion of patients with academic degrees in high school and below in the central region was higher, 49.1% (216/440) in large institutions and 47.0% (275/585) in small institutions. In terms of economics, 30.5% (521/1 708) of eastern patients reached an annual income of more than RMB 100 000, while only 2.8% (26/939) were willing to accept more than RMB 100 000 in treatment costs, and patients in the central and western regions were lower than those in the eastern region in terms of their annual income and acceptable treatment costs ( P<0.001). In terms of transportation, patients in the western region spent the longest amount of one-way transportation time, with large institutions of 30.9% (117/379) and small institutions of 29.8% (167/561) needing to spend more than 3 h; the proportion of patients in the eastern region who seek medical treatment from overseas was the highest, with 21.6% (164/758). Conclusion:The age of infertility patients in assisted reproductive institutions in China generally exceeds the optimal reproductive age of women and has a higher degree of education. Therefore, in young and people with a lower degree of education, the publicity of reproductive knowledge should be strengthened to encourage couples with fertility willingness to start preparation as early as possible. ln addition, there are more older patients in the western region, as well as the economic and transportation conditions are more unfavorable, and more attention needs to be paid at the policy level.

Objective:To describe the characteristics and medical seeking behaviors of female infertility patients in assisted reproductive institutions in China overall and geographical regions, and compare the differences among the eastern, the middle and the western regions.Methods:This study used the data from Unit 6-Analysis on the matching status of reproductive health and health care services among reproductive age population and demonstration and promotion study of diagnosis and treatment in National Key R&D Program "Reproductive Health and Major Birth Defects Prevention and Control Study" participated by the Assisted Reproductive Technology Management Department of Maternal and Child Health Care Center, Chinese Center for Disease Control and Prevention. One assisted reproductive institution with more than 1 000 and less than 1 000 oocyte retrieval cycles by in vitro fertilization techniques in 2018 was selected from 8 provincial capital cities in different regions of eastern and western China, and the questionnaire data of infertile female patients aged 20-49 years who first visited the outpatient clinics of 16 institutions were analyzed. The patient's age, degree of culture, annual personal income, try-to-conceived time, and one-way transportation time were analyzed using the frequency description, χ 2 test, Kruskal-Wallis H test and other methods. Results:A total of 3 673 female patients were finally included as study subjects. The patient's age was (31.0±4.6) years old, and 59.0% (2 156/3 660) was an undergraduate/college degree or above, with a median pregnancy test duration of 2.0 (1.3, 3.5) years. In terms of demographic characteristics, the proportion of patients over 35 years old in the eastern and western regions was greater in small institutions, 22.8% (216/948) and 26.4% (148/561), respectively. The proportion of patients with academic degrees in high school and below in the central region was higher, 49.1% (216/440) in large institutions and 47.0% (275/585) in small institutions. In terms of economics, 30.5% (521/1 708) of eastern patients reached an annual income of more than RMB 100 000, while only 2.8% (26/939) were willing to accept more than RMB 100 000 in treatment costs, and patients in the central and western regions were lower than those in the eastern region in terms of their annual income and acceptable treatment costs ( P<0.001). In terms of transportation, patients in the western region spent the longest amount of one-way transportation time, with large institutions of 30.9% (117/379) and small institutions of 29.8% (167/561) needing to spend more than 3 h; the proportion of patients in the eastern region who seek medical treatment from overseas was the highest, with 21.6% (164/758). Conclusion:The age of infertility patients in assisted reproductive institutions in China generally exceeds the optimal reproductive age of women and has a higher degree of education. Therefore, in young and people with a lower degree of education, the publicity of reproductive knowledge should be strengthened to encourage couples with fertility willingness to start preparation as early as possible. ln addition, there are more older patients in the western region, as well as the economic and transportation conditions are more unfavorable, and more attention needs to be paid at the policy level.

Background Indoor air pollution is an important risk factor affecting health of the respiratory system. Studies on indoor air pollution in China are mostly limited to the central and eastern regions, and there are few studies in the rural areas of northwest China. Objective To explore the influencing factors of lung ventilation function and its relationship with indoor air pollution in rural areas of Gansu Province based on a cross-sectional investigation. Methods A total of 399 subjects were selected from four villages in Baiyin and Yuzhong of Gansu Province. Questionnaires were used to collect demographic information, lifestyle, disease history, fuel use, and other information, and physical and functional tests were ordered such as height, weight, and lung function. The Indoor Air Pollution (IAP) exposure index was calculated based on smoking, fuel type, and weekly ventilation. IAP > 5 was defined as a high level of indoor air pollution. Lung function indexes included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, forced vital capacity as a percentage of predicted value (FVC%), and forced expiratory volume in the first second as a percentage of predicted value (FEV1%), which were used to determine pulmonary ventilation dysfunction. Logistic regression model was used to evaluate the relationship between indoor air pollution and pulmonary ventilation function, and subgroup analysis was further conducted according to home address and BMI , in order to identify the high-risk population of pulmonary ventilation dysfunction. Results The mean age of the subjects was (56.75±7.31) years old; 155 subjects (38.85%) had normal pulmonary ventilation function, and the other 244 subjects (61.14%) had impaired pulmonary ventilation function; about 89.97% of the subjects were exposed to high level of indoor air pollution (IAP > 5). We found that IAP > 5 (OR=2.327, 95%CI: 1.089-4.974) and use of bituminous coal as the main heating fuel in winter (OR=3.467, 95%CI: 1.197-10.037) increased the risk of pulmonary ventilation dysfunction after adjusting for age, BMI, residence, gender, smoking, drinking, and cardiovascular disease. The subgroup analysis results showed that no ventilation in the living room/bedroom (OR=3.460, 95%CI: 1.116-10.268) increased the risk of pulmonary ventilation dysfunction in Baiyin. Heating with coal stoves and Chinese Kang in the bedroom (OR=2.092, 95%CI: 1.030-4.247) and cooking in the bedroom in winter ( OR =2.954, 95% CI : 1.046-8.344) also increased the risk of pulmonary ventilation dysfunction in the residents with BMI≤24 kg·m⁻². IAP > 5 (OR=3.739, 95%CI: 1.147-12.182) was associated with a significantly increased risk of pulmonary ventilation dysfunction in the BMI > 24 kg·m⁻² subgroup. Conclusion The pulmonary ventilation function of rural residents in Gansu is poor, which is negatively correlated with indoor air pollution. Coal use, overweight, cooking in bedroom, and use of coal stoves and Chinese Kang for heating may increase the risk of pulmonary ventilation dysfunction, while room ventilation is a beneficial factor.

The evaluation of female fertility at first diagnosis is an important premise and basis for determining the treatment scheme of assisted reproduction. In this study, a survey was conducted among 13 assisted reproductive institutions in China to understand the evaluation indicators and detection methods of female fertility at first diagnosis in various institutions, and provide a basis for reasonable selection of indicators. The survey showed that the indicators of female fertility evaluation at first diagnosis among assisted reproductive institutions included general health indicators, ovarian reserve indicators, and uterine conditions, etc. The selection of indicators was considerably consistent, but the detection methods were quite different. Therefore, it is necessary to choose the detection method with better validity and less harm.

The evaluation of female fertility at first diagnosis is an important premise and basis for determining the treatment scheme of assisted reproduction. In this study, a survey was conducted among 13 assisted reproductive institutions in China to understand the evaluation indicators and detection methods of female fertility at first diagnosis in various institutions, and provide a basis for reasonable selection of indicators. The survey showed that the indicators of female fertility evaluation at first diagnosis among assisted reproductive institutions included general health indicators, ovarian reserve indicators, and uterine conditions, etc. The selection of indicators was considerably consistent, but the detection methods were quite different. Therefore, it is necessary to choose the detection method with better validity and less harm.