[Effects of gelatin methacrylate anhydride hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells in the treatment of full-thickness skin defect wounds in mice].

Objective: To investigate the effects of gelatin methacrylate anhydride (GelMA) hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSCs-sEVs) in the treatment of full-thickness skin defect wounds in mice. Methods: This study was an experimental study. hUCMSCs-sEVs were extracted by ultracentrifugation, their morphology was observed through transmission electron microscope, and the expression of CD9, CD63, tumor susceptibility gene 101 (TSG101), and calnexin was detected by Western blotting. The human umbilical vein endothelial cells (HUVECs), the 3rd and 4th passages of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs) were all divided into blank control group (routinely cultured) and hUCMSC-sEV group (cultured with the cell supernatant containing hUCMSCs-sEVs). The cell scratch test was performed and the cell migration rates at 6, 12, and 24 h after scratching were calculated, the cell Transwell assay was performed and the number of migration cells at 12 h after culture was calculated, and the proportion of proliferating cells was detected by 5-acetylidene-2'-deoxyuridine and Hoechst staining at 24 h after culture, with sample numbers being all 3. The simple GelMA hydrogel and the GelMA hydrogel loaded with hUCMSCs-sEVs (hereinafter referred to as hUCMSC-sEV/GelMA hydrogel) were prepared. Then the micromorphology of 2 kinds of hydrogels was observed under scanning electron microscope, the distribution of hUCMSCs-sEVs was observed by laser scanning confocal microscope, and the cumulative release rates of hUCMSCs-sEVs at 0 (immediately), 2, 4, 6, 8, 10, and 12 d after soaking hUCMSC-sEV/GelMA hydrogel in phosphate buffer solution (PBS) were measured and calculated by protein colorimetric quantification (n=3). Twenty-four 6-week-old male C57BL/6J mice were divided into PBS group, hUCMSC-sEV alone group, GelMA hydrogel alone group, and hUCMSC-sEV/GelMA hydrogel group according to the random number table, with 6 mice in each group, and after the full-thickness skin defect wounds on the back of mice in each group were produced, the wounds were performed with PBS injection, hUCMSC-sEV suspenson injection, simple GelMA coverage, and hUCMSC-sEV/GelMA hydrogel coverage, respectively. Wound healing was observed on post injury day (PID) 0 (immediately), 4, 8, and 12, and the wound healing rates on PID 4, 8, and 12 were calculated, and the wound tissue was collected on PID 12 for hematoxylin-eosin staining to observe the structure of new tissue, with sample numbers being both 6. Results: The extracted hUCMSCs-sEVs showed a cup-shaped structure and expressed CD9, CD63, and TSG101, but barely expressed calnexin. At 6, 12, and 24 h after scratching, the migration rates of HEKs (with t values of 25.94, 20.98, and 20.04, respectively), HDFs (with t values of 3.18, 5.68, and 4.28, respectively), and HUVECs (with t values of 4.32, 19.33, and 4.00, respectively) in hUCMSC-sEV group were significantly higher than those in blank control group (P<0.05). At 12 h after culture, the numbers of migrated HEKs, HDFs, and HUVECs in hUCMSC-sEV group were 550±23, 235±9, and 856±35, respectively, which were significantly higher than 188±14, 97±6, and 370±32 in blank control group (with t values of 22.95, 23.13, and 17.84, respectively, P<0.05). At 24 h after culture, the proportions of proliferating cells of HEKs, HDFs, and HUVECs in hUCMSC-sEV group were significantly higher than those in blank control group (with t values of 22.00, 13.82, and 32.32, respectively, P<0.05). The inside of simple GelMA hydrogel showed a loose and porous sponge-like structure, and hUCMSCs-sEVs was not observed in it. The hUCMSC-sEV/GelMA hydrogel had the same sponge-like structure, and hUCMSCs-sEVs were uniformly distributed in clumps. The cumulative release rate curve of hUCMSCs-sEVs from hUCMSC-sEV/GelMA hydrogel tended to plateau at 2 d after soaking, and the cumulative release rate of hUCMSCs-sEVs was (59.2±1.8)% at 12 d after soaking. From PID 0 to 12, the wound areas of mice in the 4 groups gradually decreased. On PID 4, 8, and 12, the wound healing rates of mice in hUCMSC-sEV/GelMA hydrogel group were significantly higher than those in the other 3 groups (P<0.05); the wound healing rates of mice in GelMA hydrogel alone group and hUCMSC-sEV alone group were significantly higher than those in PBS group (P<0.05). On PID 8 and 12, the wound healing rates of mice in hUCMSC-sEV alone group were significantly higher than those in GelMA hydrogel alone group (P<0.05). On PID 12, the wounds of mice in hUCMSC-sEV/GelMA hydrogel group showed the best wound epithelization, loose and orderly arrangement of dermal collagen, and the least number of inflammatory cells, while the dense arrangement of dermal collagen and varying degrees of inflammatory cell infiltration were observed in the wounds of mice in the other 3 groups. Conclusions: hUCMSCs-sEVs can promote the migration and proliferation of HEKs, HDFs, and HUVECs which are related to skin wound healing, and slowly release in GelMA hydrogel. The hUCMSC-sEV/GelMA hydrogel as a wound dressing can significantly improve the healing speed of full-thickness skin defect wounds in mice.

[Ophthalmic surgical robot-assisted retinal puncture and injection for submacular hemorrhage caused by polypoid choroidal vasculopathy: a case report].

A 65-year-old man presented with decreased visual acuity in the left eye for 1 month. The diagnosis of hemorrhagic retinal detachment (submacular hemorrhage), which was caused by idiopathic polypoid choroidal vasculopathy, was confirmed by the ultra-wide-angle fundus examination, optical coherence tomography, and B-ultrasound. A vitrectomy combined with an ophthalmic surgical robot-assisted retinal puncture and injection was performed. The recombinant tissue plasminogen activator was injected accurately by the ophthalmic surgical robot between the retinal nerve epithelium and retinal pigment epithelium through a micro-injection needle. During the 2-month follow-up, the subretinal hemorrhage was significantly regressive, the visual acuity of the left eye was improved from hand movement to 0.1, and no other complications were observed.

[Comparison of efficacy and safety between domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer].

Objective: To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. Methods: A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage ⅢB to Ⅳ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared. Results: In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05). Conclusions: The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.

FFAR4 activation inhibits lung adenocarcinoma via blocking respiratory chain complex assembly associated mitochondrial metabolism.

Despite notable advancements in the investigation and management of lung adenocarcinoma (LUAD), the mortality rate for individuals afflicted with LUAD remains elevated, and attaining an accurate prognosis is challenging. LUAD exhibits intricate genetic and environmental components, and it is plausible that free fatty acid receptors (FFARs) may bridge the genetic and dietary aspects. The objective of this study is to ascertain whether a correlation exists between FFAR4, which functions as the primary receptor for dietary fatty acids, and various characteristics of LUAD, while also delving into the potential underlying mechanism. The findings of this study indicate a decrease in FFAR4 expression in LUAD, with a positive correlation (P < 0.01) between FFAR4 levels and overall patient survival (OS). Receiver operating characteristic (ROC) curve analysis demonstrated a significant diagnostic value [area under the curve (AUC) of 0.933] associated with FFAR4 expression. Functional investigations revealed that the FFAR4-specific agonist (TUG891) effectively suppressed cell proliferation and induced cell cycle arrest. Furthermore, FFAR4 activation resulted in significant metabolic shifts, including a decrease in oxygen consumption rate (OCR) and an increase in extracellular acidification rate (ECAR) in A549 cells. In detail, the activation of FFAR4 has been observed to impact the assembly process of the mitochondrial respiratory chain complex and the malate-aspartate shuttle process, resulting in a decrease in the transition of NAD+ to NADH and the inhibition of LUAD. These discoveries reveal a previously unrecognized function of FFAR4 in the negative regulation of mitochondrial metabolism and the inhibition of LUAD, indicating its potential as a promising therapeutic target for the treatment and diagnosis of LUAD.

[Study of immunophenotypic characteristics, clinicopathological parameters and prognosis in gastric cancer microenvironment].

Objective: To explore the immunophenotypic characteristics of gastric cancer microenvironment and analyze its correlation with clinicopathological parameters and prognosis of patients. Methods: The expression levels of leukocyte differentiation antigen (CD) 8, CD4, T lymphocyte immunoglobulin mucoprotein 3 (TIM3), human forkhead box protein P3 (Foxp3) and co-localized tumor infiltrating lymphocytes (TILs) were detected in 92 cases of gastric cancer tissue [58 males and 34 females; aged M(Q1, Q3), 70(59, 77) years ] and 84 cases of paracancer tissue [57 males and 27 females, aged 70(59, 77) years] purchased from Shanghai Xinchao Biotechnology Co., Ltd., and the samples were from 28 hospitals in the sample bank. Gastric cancer and adjacent tissues were divided into high expression group and low expression group according to the optimal cut-off value of positive lymphocytepercentage. The expression of immunophenotypes in gastric cancer and adjacent tissues was analyzed. Kaplan-Meier method was used for survival analysis. Cox proportional hazard model was used to explore the prognostic factors of gastric cancer patients. Results: The optimal cut-off values of CD8, CD4, TIM3 and Foxp3 positive cells in gastric cancer were 12.73%, 1.39%, 10.77% and 2.44%, respectively. The expression of Foxp3 in gastric cancer tissues was higher than that in paracancer tissues [M (Q1, Q3), 0.93 (0.45, 2.16) vs 0.31 (0.09, 0.86), P<0.001], and the expression of CD8 [4.92 (2.34, 8.80) vs 8.81 (6.61, 12.17), P<0.001], CD4 [4.79 (1.77, 11.36) vs 8.40 (4.84, 12.77), P=0.022] and TIM3 [5.68 (2.05, 11.58) vs 7.07 (3.13, 11.43), P=0.338] were lower than that in paracancer tissues. There were significant differences in TIM3 expression in gastric cancer patients with different lymph node metastasis and clinical stage (all P<0.05). The 5-year survival rate of patients with high CD4 expression, low TIM3 expression and low Foxp3 expression in gastric cancer tissues was poor, among which the high CD4 expression and low CD4 expression groups were 29.3% and 64.7%, respectively; The high and low TIM3 expression groups were 60.9% and 30.4%, respectively; The high and low Foxp3 expression groups were 64.3% and 33.3%, respectively (all P<0.05). The optimal cut-off values of CD8+TIM3+TILs, CD4+TIM3+TILs, CD8+Foxp3+TILs and CD4+Foxp3+TILs were 3.86%, 0.23%, 0.08% and 0.76%, respectively. Colocalization analysis showed that the expression of CD8+Foxp3+TILs in gastric cancer tissues was higher than that in adjacent tissues(all P<0.05). Multivariate Cox regression analysis showed that high expression of CD4 (HR=3.079, 95%CI: 1.350-7.024,P=0.008), low expression of TIM3 (HR=0.428, 95%CI: 0.208-0.879, P=0.021) and low expression of Foxp3 (HR=0.288, 95%CI: 0.121-0.687, P=0.005) were the influencing factor for the 5-year survival rate of patients with gastric cancer after operation. Conclusions: Gastric cancer tissues have complex immune microenvironment characteristics. The expression of CD4, TIM3 and Foxp3 is closely related to the prognosis of patients.

Synergistic effects of electroacupuncture and bone marrow stromal cells transplantation therapy in ischemic stroke.

OBJECTIVE: Animal studies and clinical trials demonstrated the effectiveness of a combination of transplanted bone marrow stromal cells (BMSC) and electroacupuncture (EA) treatment in improving neurological deficits. However, the ability of the BMSC-EA treatment to enhance brain repair processes or the neuronal plasticity of BMSC in ischemic stroke model is unclear. The purpose of this study was to investigate the neuroprotective effects and neuronal plasticity of BMSC transplantation combined with EA in ischemic stroke. MATERIALS AND METHODS: A male Sprague-Dawley (SD) rat middle cerebral artery occlusion (MCAO) model was used. Intracerebral transplantation of BMSC, transfected with lentiviral vectors expressing green fluorescent protein (GFP), was performed using a stereotactic apparatus after modeling. MCAO rats were treated with BMSC injection alone or in combination with EA. After the treatment, proliferation and migration of BMSC were observed in different groups by fluorescence microscopy. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry were performed to examine changes in the levels of neuron-specific enolase (NSE) and nestin in the injured striatum. RESULTS: Epifluorescence microscopy revealed that most BMSC in the cerebrum were lysed; few transplanted BMSC survived, and some living cells migrated to areas around the lesion site. NSE was overexpressed in the striatum of MCAO rats, illustrating the neurological deficits caused by cerebral ischemia-reperfusion. The combination of BMSC transplantation and EA attenuated the expression of NSE, indicating nerve injury repair. Although the qRT-PCR results showed that BMSC-EA treatment elevated nestin RNA expression, less robust responses were observed in other tests. CONCLUSIONS: Our results show that the combination treatment significantly improved restoration of neurological deficits in the animal stroke model. However, further studies are required to see if EA could promote the rapid differentiation of BMSC into neural stem cells in the short term.

[Application of the two-step sentinel lymph node biopsy with double-tracer in early staged endometrial cancer].

Objective: To explore the feasibility and clinical value of sentinel lymph node (SLN) biopsy through cervix-uterine combined two-step injection with two tracers in patients with early stage endometrial cancer. Methods: From July 2019 to April 2021, a total of 73 patients, aged (54.2±3.3) year, who were preoperatively diagnosed as stage Ⅰ-Ⅱ endometrial cancer (including 56 low-risk patients and 17 medium-high risk patients) in Affiliated Hospital of Qingdao University were selected. According to the different sites of tracer injection, the patients were randomly divided into three groups: cervical injection group (25 cases): 1 ml of nano-carbon was used to inject at 3 and 9 o'clock in the cervix; uterine injection group (21 cases): the magnetic resonance imaging examination was performed to determine the location of the lesion, and 4 ml of methylene blue was injected into the uterine body at 2 sites where the lesion was located; combined injection group (27 cases): cervical injection of nano-carbon (1 ml) combined with uterine injection of methylene blue (4 ml). The SLN in all patients were identified under laparoscopy, removed, and followed by frozen pathological examination. Pathological ultra-staging was performed if the postoperative pathological outcome of SLN was negative. The total detection rate of SLN, bilateral pelvic SLN detection rate, sensitivity, negative predictive value, and location of SLN in each group were calculated and compared. Results: (1) In 73 patients with endometrial cancer, the overall detection rate of SLN was 88% (64/73), the detection rate of bilateral pelvic SLN was 67% (49/73), and the detection rate of para-aortic SLN was 49% (36/73). The overall detection rate of SLN (71%, 15/21) and bilateral pelvic SLN (43%, 9/21) in the intrauterine injection group were significantly lower than those in the cervical injection group [92% (23/25), 76% (19/25), respectively] and the combined injection group [96% (26/27), 78% (21/27), respectively; all P<0.05]; the detection rate of para-aortic SLN in the cervical injection group (28%, 7/25) was significantly lower than those in the intrauterine injection group and combined injection group [52% (11/21) and 67% (18/27), respectively; both P<0.05]. Among 73 cases with endometrial cancer, 9 had lymph node metastasis confirmed by postoperative pathological examination, 8 of them had lymph node metastasis detected by SLN and 1 had no lymph node metastasis detected by SLN, with a total sensitivity of 89% and a negative predictive value of 98%. The sensitivity and negative predictive value of cervical injection group and combined injection group were 100%, while the sensitivity and negative predictive value of intrauterine injection group were 67% and 95%. Among 56 low-risk patients, only one patient with lymph node metastasis was confirmed by postoperative pathology by SLN detection, and the metastasis rate was 2% (1/56), and the sensitivity and negative predictive value were 100%. Lymph node metastasis was confirmed in 8 of 17 patients (8/17) with a sensitivity of 88% and a negative predictive value of 90%. (2) A total of 459 SLN were detected in 73 endometrial cancer patients, with the highest proportion of external iliac (33.3%, 153/459).The obturator foramen was 25.3% (116/459), para-aortic 19.6% (90/459), iliac 12.0% (55/459), and presacral 9.8% (45/459). The proportion of para-aortic SLN in the cervical injection group was 12.4% (21/169), which were significantly lower than that in the intrauterine injection group and the combined injection group [27.4% (26/95) and 22.1% (43/195), respectively; both P<0.05]. (3) Pathological super-staging results: among 64 patients with negative SLN routine paraffin pathology, 4 cases of lymph node micro-metastases and 1 case of isolated tumor cell metastasis were detected, and the SLN micro-metastases rate was 8% (5/64), including 2 cases of low-risk patients and 3 cases of medium-high risk patients. Conclusions: SLN biopsy has high sensitivity and negative predictive value in patients with early endometrial cancer and could be used as an alternative to systematic lymph node dissection in low-risk patients. The SLN mapping through cervical-uterine combined injection could further improve the detection rate effectively and avoid the missed detection of positive para-aortic lymph node, especially for high-risk patients or patients with fundal tumor involvement.

[Establishment and effect evaluation of nomogram model for diagnosis and prediction of pulmonary hypertension in patients with chronic obstructive pulmonary disease].

Objective: To construct a diagnostic and predictive model for chronic obstructive pulmonary disease complicated with pulmonary hypertension (COPD-PH) and evaluate its effect. Methods: A total of 1 514 COPD patients treated in 5 hospitals from January 1, 2014 to December 31, 2019 were retrospectively collected and divided into training cohort (1 072 cases) and validation cohort (442 cases) according to the ratio of 7∶3 according to the inclusion time. Data including demographic data, smoking status, history of disease, and clinical examination were collected through patient medical records and electronic medical record systems. Multivariate logistic regression models were used to explore the related factors of COPD-PH, and the nomogram model was constructed using the "rms" program package. The calibration curve was used to evaluate the consistency between the prediction probability of the model and the actual results. The C index and the area under the receiver operating characteristic curve (ROC) were used to evaluate the discrimination of the model. The decision curve analysis (DCA) was used to evaluate the clinical practicability of the model. Results: In the training cohort, 3.7%, 15.2% and 81.1% were aged 50-59, 60-69 and ≥70 years, respectively, which were significantly different from the age composition of the validation cohort (7.9%, 27.8% and 64.3%, respectively) (P=0.041). There was no significant difference between the training cohort (79.4%) and the validation cohort (84.6%) (P=0.243). Multivariate logistic regression analysis of the training cohort showed that age ≥70 years [OR (95%CI): 3.32 (1.49-7.36)] and smoking status [former (current) smoking, OR (95%CI)] were 3.67 (2.51-5.37) and 2.04 (1.44-2.90), respectively], NT-probNP≥1 400 ng/L[OR (95%CI): 9.88 (6.23-15.66)], right atrial diameter [OR (95%CI): 1.11 (1.07-1.15)] was COPD-related factors of PH, based on the above factors-PH nomogram COPD model was set up and develop for online tools (https://ph-666.shinyapps.io/zhonghua-PH/). The calibrated C index (95%CI) of the training cohort and the validation cohort were 0.82 (0.77-0.87) and 0.77 (0.68-0.86), respectively. The calibration curve was close to the diagonal in both the training cohort and the validation cohort. The AUC (95%CI) of the nomogram model was 0.82 (0.80-0.85) in the training cohort and 0.77 (0.73-0.82) in the validation cohort. ROC curve showed that the optimal threshold in the training cohort was 0.60, and the sensitivity and specificity under this value were 0.74 and 0.78, respectively; the optimal threshold for the validation cohort was 0.70, and the sensitivity and specificity under this value were 0.76 and 0.65, respectively. DCA analysis showed that the nomogram model provided better net benefits than the all-variable selection and no-variable selection strategies with threshold probabilities greater than 15.0% and 13.0% in the training and validation cohorts, respectively. Conclusions: The nomogram model for the diagnosis and prediction of COPD-PH is simple and accurate, which has a good clinical application prospect.

Risk factors for the development of hepatocellular carcinoma in Chengdu: a prospective cohort study.

OBJECTIVE: To investigate the incidence of hepatocellular carcinoma (HCC) in Chengdu, identify the risk factors for the development of HCC in Chengdu and provide a reference for the prevention of HCC. PATIENTS AND METHODS: The study population was recruited from Chengdu, Sichuan Province, China. The study group recruited volunteers in Chengdu from 2007 to 2012, conducted a baseline survey, and subsequently conducted long-term follow-up until December 31, 2019. A total of 22,525 study subjects were enrolled, excluding those who reported a previous history of liver disease, malignancy, and HCC within three months of enrollment. Cox proportional risk regression models were used to screen and determine the various risk factors and their hazard ratios (HR) for HCC in Chengdu, as well as to determine whether the association between other risk factors and HCC was modified by gender. RESULTS: The study population had a median follow-up of 5.35 years, and a total of 142 people developed HCC, with an incidence rate of 0.71%. Analysis of the multifactorial Cox proportional risk regression model showed that age (age 10 years for 1 group, HR= 1.98, 95% CI: 1.86-2.11, p<0.001), current smoking (HR= 1.25, 95% CI: 1.07-1.31, p=0.031), weekly consumption of pickled vegetables (HR= 1.70, 95% CI: 1.49-1.81, p=0.003) and consumption of pickled vegetables daily (HR= 1.36, 95% CI: 1.21-1.42, p=0.021) were risk factors for HCC, and women (HR= 0.39, 95% CI: 0.28-0.55, p=0.002) and the use of air conditioning (10 years for 1 group, HR= 0.79, 95% CI: 0.68-0.83, p=0.002) were protective factors against HCC. Further analysis revealed that the association between length of time using air conditioning and HCC was heterogeneous among men and women (p=0.007) and that there was an interaction between sex and use of air conditioning in the association with HCC development (p<0.001). CONCLUSIONS: The Chengdu population has a high incidence of HCC and numerous risk factors for HCC. There is a synergistic interaction between sex and length of time using air conditioning in their role in the development of HCC.

[Association between polymorphism of CASP and NOX3 with risk of noise-induced hearing loss].

Objective: To explore the effect of gene polymorphism on workers suffering from noise induced hearing loss (NIHL) . Methods: In May 2019, a case-control study was conducted to select noise exposed workers in five factories in Zhejiang Province from 2017 to 2018. The average hearing threshold of binaural high frequency (3, 4, 6 kHz) was >25 dB (A) as the NIHL group, and the hearing threshold of any language frequency (0.5, 1, 2 kHz) was ≤25 dB (A) as the non NIHL group, with 307 people in each group. The general demographic data, occupational history, pure tone audiometry results and oral swab mucosal samples of noise exposed workers were collected, and the DNA of oral mucosal cells was extracted. The relationship between genetic risk score (GRS) and NIHL was analyzed, single nucleotide polymorphisms (SNP) were genotyped, the relationship between genotype and NIHL was analyzed by logistic regression, and the relationship between haplotype and NIHL was analyzed by R language. Results: After adjusting for gender, age, education and working years, the risk of NIHL among workers carrying cysteine-aspartic acid protease 3 gene (CASP3) rs1049216 recessive model GG genotype, rs6948 recessive model TT genotype, NADPH oxidase 3 gene (NOX3) rs12195525 additive model GT genotype and dominant model TT+GT genotype decreased (P<0.05) , the risk of disease was higher in workers with AA genotype carrying cysteine-aspartic acid protease 7 gene (CASP7) rs12415607 additive model (P<0.05) . There was a strong linkage disequilibrium (LD) relationship between rs1049216 and rs6948 (D'>0.8) . Haplotype AT and GG composed of rs1049216-rs6948 increased the risk of NIHL (P<0.05) . The risk of NIHL increased with the increase of GRS (OR=2.69, P<0.05) . Conclusion: Genotype polymorphisms at rs1049216 and rs6948 (CASP3) , rs12195525 (NOX3) , rs12415607 (CASP7) may be associated with susceptibility to NIHL.

[Clinical characteristics and CYP17A1 gene mutation analysis in patients with 17α-hydroxylase/17, 20-lyase deficiency and testicular tumor].

The 17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is a rare disease. The clinical characteristics and gene mutation of 2 late-diagnosed 17-OHD patients with testicular tumor admitted to our hospital from March 2018 to February 2019 were analyzed retrospectively. The two 17-OHD patients were female (46, XY). Laparoscopic abdominal exploration found undeveloped testicles in grey-yellow or grey-red in the groin and iliac fossa. The testicles were removed and showed malignancy in pathology study. Sequencing of the CYP17A1 gene identified c.1247G>A/c.1427T>C and c.985_987delTACinsAA/c.1306G>A complex heterozygous mutations. Taking together, the possibility of 17-OHD should be considered in patients with hypertension, hypokalemia, adrenal adenomatoid hyperplasia together with 46, XY gonadal dysplasia, so as to make early diagnosis and treatment, and avoid dysplastic testicular turning to malignancy.

[Analysis of middle ear function of the patients with cleft palate after palatoplasty].

Objective: To investigate the middle ear function of the patients with cleft palate pre and post palatoplasty. Methods: 76 patients with cleft palate were investigated by clinical history and audiology examinations including electric otoscopy,tympanometry and click-ABR threshold. Results: The risk for middle ear function decreased with advancing age in the first 5 years. It was noticed that the otologic outcomes was related to the CP type. During long time follow-up, the frequency with the middle ear function disorder was always high within the CP patients but the proportion of the patients received tympanostomy tubes was low relatively. The prevalence of middle ear dysfunction did not differ with the time of cleft palate repair. Conclusion: The patients with cleft palate have middle ear function dysfunction in a long period of time,therefore a standard long-time follow-up system is necessary.

[Impact of enhanced recovery after surgery strategy on early postoperative quality of recovery in patients undergoing laparoscopic surgery for gynecologic malignancy].

Objective: To investigate the impact of perioperative anesthesia management with enhanced recovery after surgery (ERAS) strategy on postoperative recovery in patients undergoing laparoscopic surgery for gynecologic malignancy. Methods: Ninety patients undergoing laparoscopic surgery for gynecologic malignancies from April 2018 to April 2019,aged 18-65 years,with American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, were recruited and randomly divided into two groups (n=45) using a random number table:ERAS group (group E) and control group (group C). Patients in group E received general anesthesia combined with transverses abdominis plane block and a series of interventions to optimize anesthetic and perioperative management, while patients in group C were treated with routine anesthesia management. Quality of Recovery-40 questionnaire (QoR-40) was administered to assess the early postoperative quality of recovery on 1 day before surgery, and at 24 and 48h after surgery. C-reactive protein (CRP) before and after the operation were evaluated. The incidence of nausea, vomiting and shivering, the time of first exhaust, ambulation, resumption of normal diet, postoperative hospital stay and complications were recorded. Results: The scores of QoR-40 [M(Q1, Q3)] in Group E were 175(171, 179) and 185(183, 189) at 24 h and 48 h after operation, which were higher than those in group C [162(160, 167) and 180(179, 183)] (both P<0.01). The levels of CRP in both group E and group C increased at 24 h and 72 h after operation. Moreover, the extent of increasing level of CRP in group C was much higher than that in group E [(39.8±18.0) mg/L vs (13.4±6.3) mg/L, (16.6±8.6) mg/L vs (6.7±2.5) mg/L] at 24 h and 48 h after operation (both P<0.01). Compared with group C, the numerical rating scale (NRS) for nausea decreased significantly in group E [0(0, 2) vs 3 (0, 5), P<0.01]. Meanwhile, the incidence of vomiting and shivering in group E was lower than that in group C [8.9% (4/45) vs 26.7% (12/45); 11.1% (5/45) vs 31.1% (14/45); both P<0.05]. The time of first exhaust, ambulation and resumption of normal diet in group E was (14±6) h, 6(6, 13) h and 1(1, 2) d, respectively, which was markedly shorter than that in group C [(25±10) h, 21(19, 27) h and 3(2, 3) d] (all P<0.01). Overall, the postoperative length of hospital stay reduced significantly for patients who followed the ERAS protocol [7(5, 11) d vs 10(7, 14) d, P<0.01]. The incidence of postoperative complications was 17.8% (8/45) and 37.8% (17/45) in group E and group C, respectively, with a significant difference (P<0.05). Conclusion: Implementation of ERAS anesthesia management in gynecologic oncology patients undergoing minimally invasive surgery alleviates perioperative discomfort, decreases surgical stress response, and improves the early postoperative quality of recovery.

[Diagnostic value of diffusion-weighted imaging and conventional magnetic resonance imaging in testicular tumor].

Apparent diffusion coefficient(ADC) of magnetic resonance imaging≤0.90×10-3 mm2/s and T2-hypointensity, intratuminal septa, and peritumoral infiltration could achieve best diagnostic efficiency. ADC values and cyst or necrosis were independent predictors for the differential diagnosis of nonseminomatous germ cell tumor versus seminoma and nonseminomatous germ cell tumor versus lymphoma. ADC value and intratuminal septa were independent predictors for the differential of seminoma versus lymphoma.