In environmental epidemiological research, extensive non-random environmental exposures and complex confounding biases pose significant challenges when attempting causal inference. In recent years, the introduction of causal inference methods into observational studies has provided a broader range of statistical tools for causal inference research in environmental epidemiology. The instrumental variable (IV) approach, as a causal inference technique for effectively controlling unmeasured confounding factors, has gradually found application in the field of environmental epidemiological research. This article reviewed the basic principles of IV and summarized the current research progress and limitations of applying IV for causal inference in environmental epidemiology. IV application in the field of environmental epidemiology is still in the initial stage. Rational use of IV and effective integration with other causal inference methods will become the focus of the development of causal inference in environmental epidemiology. The aim of this paper is to provide a methodological reference and basis for future studies involving causal inference to target population health effects of environmental exposures in China.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Due to the non-targeted release and low solubility of anti-gastric cancer agent,apatinib(Apa),a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects.In order to avoid these drawbacks,lipid-film-coated Prussian blue nanoparticles(PB NPs)with hyaluronan(HA)modification was used for Apa loading to improve its solubility and targeting ability.Furthermore,anti-tumor compound of gamabufotalin(CS-6)was selected as a partner of Apa with reducing dosage for combinational gastric therapy.Thus,HA-Apa-Lip@PB-CS-6 NPs were constructed to synchro-nously transport the two drugs into tumor tissue.In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor(VEGFR)and matrix metalloproteinase-9(MMP-9).In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs adminis-tration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects.In summary,we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer(GC)therapy.

Objective To investigate the effect of cervical manual stratified anastomosis and anastomosis with tube stapler on the recent complications in thoracic laparoscopy combined with radical resection of esophageal cancer.Methods From February 2019 to April 2022,a total of 196 patients who underwent endoscopic surgery for esophageal cancer who met the study criteria were divided into the manual group(87 cases)and the tubulostomy group(109 cases)according to the different ways of gastro-esophageal cervical anastomosis.The incidence of cervical surgery time,total operation time,postoperative anastomotic fistula,anastomotic stenosis and other complications of the two groups were evaluated,and the differences in treatment effects between the two groups were compared.Results The preoperative basic conditions of patients in the manual group and the tube kiss group were comparable,and the cervical anastomosis time in the tube kiss group[(23±3.57)min]was shorter than that in the manual group[(31±4.5)min](P＜0.05),but there was no statistical significance in the overall operation time between the two groups(P＞0.05).The comparison of postoperative anastomotic fistula and anastomotic stenosis between the two groups showed that the manual group was significantly lower than the tube kiss group,and the difference was statistically significant(P＜0.05).Conclusion In thoracic laparoscopic combined with esophageal cancer surgery,cervical manual stratified anastomosis can reduce the incidence of postoperative anastomotic complications.

Objective:To explore the changes in peripheral blood monocyte count in children with adenovirus pneumonia (AP) and its value in severity assessment.Methods:A retrospective analysis was conducted on the peripheral blood differential leucocyte count of 139 children with AP, and they were compared with 61 healthy children.Results:Compared with the control group, the monocyte count in AP patients was higher ( P<0.001). In the early stage of hospitalization, the monocyte counts in the severe adenovirus pneumonia (SAP) group and the general adenovirus pneumonia (GAP) group were both higher than that in the control group (both P<0.05), while the monocyte count in the SAP group was lower than that in the GAP group ( P<0.05). In the later stage of hospitalization, the monocyte count in the GAP group decreased ( P<0.05), while the monocyte count in the SAP group did not decrease significantly ( P>0.05), and the monocyte count in the SAP group was higher than that in the GAP group ( P<0.05). Multivariate logistic regression analysis showed that a lower monocyte count in the early stage of hospitalization was one of the independent risk factors for SAP ( P=0.004). The area under the receiver operating characteristic (ROC) curve (AUC) of monocyte count in the early stage of hospitalization used for the prediction of SAP was 0.742, with an optimal cutoff value of 1.05×10 9/L, a sensitivity of 74.3% and a specificity of 63.5%. Conclusions:Children with AP may have a varying degree of increase in peripheral blood monocyte count. Compared with children with GAP, children with SAP showed a lower degree of increase in monocyte count, but a slower decrease. Peripheral blood monocyte count can serve as one of the potential indicators for assessing the risk of the progression of AP in children.

Background:In the clinical setting, the effect of intra-abdominal hypertension on the human body is dependent on time, but its role is not yet clear.Objective:To investigate the effect of the duration of intra-abdominal hypertension (IAH) on the prognosis of critically ill patients.Methods:This prospective cohort study enrolled 256 IAH patients who were admitted to the Surgical ICU of 10 Grade A hospitals in Fujian Province from January 2018 to December 2020. The duration of IAH (DIAH) was obtained after monitoring IAP, and ICU length of stay, duration of mechanical ventilation, duration of continuous renal replacement therapy (CRRT) and average daily energy intake from enteral nutrition during ICU stay were observed and recorded. The correlation was analyzed by Spearman rank correlation. The patients were divided into the survival group and the death group according to their survival state at 60 days after enrollment. Thereafter, clinical characteristics between the two groups were compared. Multivariable logistic regression was used to study and validate the relationship between DIAH and 60-day mortality. The receiver operating characteristics (ROC) curve was established to evaluate the predictive abilities of DIAH on the mortality risk.Results:In critically ill patients, DIAH was positively correlated with duration of mechanical ventilation ( r=0.679, P<0.001), duration of CRRT ( r=0.541, P<0.001) and ICU length of stay ( r=0.794, P<0.001), respectively. In addition, there was a negative correlation between DIAH and average daily energy intake from enteral nutrition ( r=-0.669, P<0.001). After multivariable adjustment, DIAH was an independent risk factor for 60-day mortality in critically patients with IAH ( OR=1.05, 95% CI: 1.01-1.12; P = 0.012), and exhibited a linearity change trend relationship with mortality risk. The ROC curve analysis of DIAH showed that the area under ROC curve (AUC) was 0.825 (95% CI: 0.763~0.886, P<0.01). When the cut-off value was 16.5 days, the sensitivity was 78.4% and the specificity was 75.4%. Conclusions:DIAH is an important risk factor for prognosis in critically ill patients. Early identification and rapid intervention for the etiology of IAH should be performed to shorten DIAH.

0bjective: To establish a three-dimensional finite element model of mandible and study the transverse displacement of proximal segment after Bilateral Sagittal Split Ramus Osteotomy (BSSRO) with different retrogression amounts during mastication. Methods: DICOM data of a skull model were processed with MIMICS and ANSYS software, reconstructing the 3D model including the teeth and temporomandibular joint in order to simulate BSSRO and evaluate the transverse displacement of proximal segment with different retrogression amounts during mastication. Results: The mean of proximal segment width change were 2.955 mm and 3.490 mm, when retrogression amounts of distal segmentwere 3 mm and 8 mm, respectively.No significant difference between the two groups were found (P=0.131). Meanwhile the displacement color scale of the 3D finite element models showed that the apparent transverse displacement distribution of the proximal segment was measured around the gonial area, decreased from the exterior to the interior. Conclusions The mandibular angle width was significantly expanded right after BSSRO. The masticatory muscle system and single cortical fixation system played an important role in expanding the width of proximal segment. However there was no correlation between the widening effect and retrogression amounts of distal segment of mandible.

Objective: To evaluate the surgical prediction accuracy of Proplan CMF software for zygomatic reduction surgery using L-shaped osteotomy. Methods: Pre-and-postoperative 1-year CBCT data of 26 patients with zygomatic arch hypertrophy were imported in Proplan CMF software during 2014 Jan. to 2016 Jun., the 3D models were reconstructed for simulation of L-shaped osteotomy, characteristic landmarks were selected and 3D point measurement system was established. The measurement result were analyzed by one-way ANOVA. Meanwhile, the overlap color grading charts of preoperative and simulated images were also observed. Results: The facial width, bilateral zygomatic process angle and facial width index were [(128.56±2.72) mm, (106.87±2.53)°, (108.56±3.02)°and 1.41±0.03] in postoperative result, [(129.49±2.26) mm, (108.68±2.40)°, (108.85±3.02)°and 1.42±0.03]in simulated result and [(135.45±2.45) mm, (102.50±2.60)°, (103.41±2.56)°and 1.48±0.05] in preoperative result, with significant difference between preoperative and postoperative result, or between preoperative and simulated result (P<0.05), while no significance between postoperative and simulated result (P>0.05). The soft tissue zygomatic process distance was(153.25±2.58) mm in preoperative result, (150.23±2.76)mm in postoperative result , (149.36±3.27)mm in simulated result, with no significance between any of two groups result (P>0.05). The zygomatic process distance and bilateral zygomatic process tragal distance were (126.35±2.56) mm, (68.75±2.15) mm and(68.86±3.21) mm in postoperative result, showing significant differences compared with preoperative result [(120.16±3.18) mm, (74.58±3.19) mm and(76.14±3.15) mm] and simulated result [(118.86±3.45) mm, (73.85±3.57) mm and(76.87±2.58) mm] respectively(P<0.05), while zygomatic arch distance was not statistically different among the three groups(P>0.05). It indicated that predictive accuracy of facial width, facial width index, zygomatic process angle, soft tissue zygomatic arch distance was high but the soft tissue zygomatic process distance and zygomatic process tragal distance was relatively low. Meanwhile, the color overlay image showed that predictive accuracy was not good in the zygomatic region while the zygomatic arch area was high. Conclusions The predictive accuracy of Proplan CMF software for zygomatic arch hypertrophy is relatively high except for the zygomatic region. Further improvement of the CMF software is needed.

Objective To investigate whether miR-200b suppresses proliferation and induces apoptosis of non-small cell lung cancer cells by targeting DNMT3A. Methods A qRT-PCR was employed for detecting the expression of miR-200b in different non-small cell lung cancer cells and human bronchial epithelial cells. A549 cells were transfected with miR-200b mimics, scramble, DNMT3A-siRNA and control-siRNA, respectively. The scramble and control-siRNA were served the negative control of miR-200b mimics and DNMT3A-siRNA, respectively. Western blot assay was conducted to detect the expression of DNMT3A protein in A549 cells. MTT and Annexin V/propidium iodide staining were employed to detect the proliferation ability and apoptosis rate of A549 cells. The effects of miR-200b mimics and DNMT3A-siRNA on the proliferation and apoptosis rate of A549 cells were compared between groups. Results Results of qRT-PCR showed that the expression of miR-200b was significantly down-regulated in A549, H1299, L78 and H460 cells than that of 16HBE cells. Among them, the most obviously reduction was found in A549 cells (P<0.05). Western blot assay showed that the level of DNMT3A protein was inhibited by restored miR-200b or knock-down DNMT3A in A549 cells. After transfection of miR-200b mimics or knock-down DNMT3A for 48 h, 72 h and 96 h, MTT showed that the OD values, which reflected the optical density of cell proliferation were significantly lower than those in the control group (P<0.05). Annexin V/propidium iodide staining showed that apoptosis rates of A549 cells after transfection of miR-200b mimics or knock-down DNMT3A were (23.33%±0.90%and 20.41%±0.70%), compared with the control group (5.28%± 0.55%and 5.68%±0.47%, P<0.01). Conclusion miR-200b suppresses cell proliferation and induces apoptosis by targeting DNMT3A in non-small cell lung cancer.