Matrix Li-Yau-Hamilton estimates under Ricci flow and parabolic frequency.

We prove matrix Li-Yau-Hamilton estimates for positive solutions to the heat equation and the backward conjugate heat equation, both coupled with the Ricci flow. We then apply these estimates to establish the monotonicity of parabolic frequencies up to correction factors. As applications, we obtain some unique continuation results under the nonnegativity of sectional or complex sectional curvature.

Requisite role of dorsal raphé in contextual cocaine-memory reconsolidation.

Memory reconsolidation is a process by which labile drug memories are restabilized in long-term memory stores, permitting their enduring control over drug-seeking behaviors. In the present study, we investigated the involvement of the dorsal raphé nuclei (DRN) in cocaine-memory reconsolidation. Sprague-Dawley rats (male, female) were trained to self-administer cocaine in a distinct environmental context to establish contextual drug memories. They then received extinction training in a different context. Next, the rats were re-exposed to the cocaine-predictive context for 15 min to reactivate their cocaine memories or remained in their home cages (no-reactivation control). Memory reactivation was sufficient to increase c-Fos expression, an index of neuronal activation, in the DRN, but not in the median raphé nuclei, during reconsolidation, compared to no reactivation. To determine whether DRN neuronal activity was necessary for cocaine-memory reconsolidation, rats received intra-DRN baclofen plus muscimol (BM; GABAB/A agonists) or vehicle microinfusions immediately after or 6 h after a memory reactivation session conducted with or without lever access. The effects of DRN functional inactivation on long-term memory strength, as indicated by the magnitude of context-induced cocaine seeking, were assessed 72 h later. Intra-DRN BM treatment immediately after memory reactivation with or without lever access attenuated subsequent context-induced cocaine-seeking behavior, independent of sex. Conversely, BM treatment in the adjacent periaqueductal gray (PAG) immediately after memory reactivation, or BM treatment in the DRN 6 h after memory reactivation, did not alter responding. Together, these findings indicate that the DRN plays a requisite role in maintaining cocaine-memory strength during reconsolidation.

[Effects of cognition-related lifestyles on early cognitive decline in community older adults in China].

Objective: To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline. Methods: The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline. Results: In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 (OR=0.683, 95%CI: 0.457-1.019; OR=0.623, 95%CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 (OR=0.491, 95%CI: 0.297-0.812; OR=0.556, 95%CI: 0.332-0.929; trend P=0.024). Conclusion: Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

[Efficacy and safety of endovascular therapy after 24 h from ischemic stroke onset in patients with acute anterior circulation ischemic stroke].

Objective: To explore the effectiveness and safety of endovascular treatment (EVT) for patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h. Methods: In this retrospective cohort study, data were extracted from patients who underwent endovascular treatment for acute anterior circulation ischemic stroke at the First Hospital of Jilin University from February 2019 to April 2022. A total of 569 patients were included, with a mean age of 63 (54-70) years. Among them, 398 (69.9%) were male. The patients were divided into two groups based on symptom onset time:>24 h group and≤24 h group. Propensity score matching (PSM) was used to match the patients in a 1︰1 ratio between the>24 h group and the≤24 h group. Logistic regression was used to evaluate the impact of symptom onset time on outcome events. Results: Before PSM, compared with≤24 h group, the>24 h group had a younger age [56 (48, 64) vs. 64 (55, 70), Z=-3. 60, P<0.001]; lower proportion of prior atrial fibrillation [1.8% (1/57) vs. 21.1% (108/512), χ2=12.39, P<0.001]; lower proportion of wake-up stroke [7.0% (4/57) vs. 27.7% (142/512), χ2=11.54, P<0.001]; lower baseline NIHSS score [11.0 (7.5, 14.0) vs. 13.0 (10.0, 16.0), Z=-3.22, P<0.001]; and a higher American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR) grading (P<0.001). After PSM, there were no significant differences in baseline characteristics between the two groups. There was no significant difference in the proportion of patients with a modified Rankin Scale (mRS) score≤2 at 90 days after surgery between the two groups (before matching: 42.0% vs. 40.4%, OR=0.745, 95%CI 0.407-1.362, P=0.339; after matching: 51.8% vs. 39.3%, OR=0.511, 95%CI 0.212-1.236, P=0.136). No significant differences were observed in the incidence of any safety outcomes between the>24 h group and the≤24 h group. Conclusion: For patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h, EVT is feasible after strict radiological screening and has similar safety and effectiveness as for patients with symptom onset under 24 h.

[Lactate promotes HMGB1 phosphorylation and release via Akt signaling pathway in gastric cancer cells HGC-27].

Objective: To investigate the molecular mechanism of how lactate induces high mobility group box 1 (HMGB1) release. Methods: Gastric cancer HGC-27 cells were divided into the control group and the lactate group (The cells were treated with lactate for 6 h). The level of HMGB1 in the cell culture medium was detected by enzyme-linked immunosorbent assay (ELISA), the localization of HMGB1 was detected using laser confocal microscopy, and the nuclear translocation of HMGB1 was detected using the nucleoplasmic separation assay. The phosphorylation and acetylation levels of HMGB1 were determined by co-immunoprecipitation, and Western blot was used to measure the phosphorylation of Akt and protein kinase C (PKC). HGC-27 cells were first treated with lactate and LY294002, the inhibitor of Akt, and then the phosphorylation of HMGB1 and Akt was analyzed by co-immunoprecipitation and Western blot, respectively. The localization of HMGB1 in cells was detected by laser confocal microscopy. EdU and Transwell assays were used to detect the proliferation and migration abilities of HGC-27 cells, respectively. HGC-27 cells were then injected into the BALB/C null mice for subcutaneous tumor implantation. Mice in the lactate group were intraperitoneally injected with lactate (0.2 g/kg/2 d), while those in the control group were intraperitoneally injected with an equal amount of PBS for 20 consecutive days. ELISA was used to detect the HMGB1 levels in the blood samples taken from the medial canthus vein of the mice, while co-immunoprecipitation and Western blot were used to detect the phosphorylation of HMGB1 and Akt in tumor tissue proteins, respectively. Results: The release levels of HMGB1 in the lactate group were (2 995.00±660.91) pg/ml and (696.33±22.03) pg/ml, after lactate treatment for 6 h and 12 h, respectively, both higher than those in the control group (485.00±105.83) pg/ml (P<0.001 and P=0.028, respectively). After lactate treatment for 6 h, the relative expression of HMGB1 protein in the cytoplasm of HGC-27 cells was 1.13±0.09, higher than that of the control group (0.83±0.07, P=0.001), while the relative expression of HMGB1 in the nucleus was 0.79±0.06, lower than that of the control group (1.07±0.06, P=0.007). The phosphorylation level of HMGB1 reached 1.41±0.09, which was higher than that of the control group (0.97±0.10, P=0.031). The phosphorylation level of Akt was 11.16±0.06, higher than that of the control group (0.91±0.022, P=0.002). The phosphorylation level and nuclear translocation of HMGB1 induced by lactate decreased obviously after Akt inhibition; the proliferation and migration abilities induced by lactate were also obviously inhibited after Akt inhibition. In vivo, the HMGB1 level in the peripheral blood was (1 280.70±389.66) pg/ml in the lactate group, which was obviously higher than that in the control group (595.11±44.75) pg/ml (P=0.008), and the phosphorylation levels of HMGB1 and Akt in tumor tissues in the lactate group were obviously enhanced compared with the control group. Conclusion: Lactate induces HMGB1 release through enhancing HMGB1 phosphorylation via the Akt signaling pathway.

[Changes of brain network in patients with insomnia following radiotherapy for cervical cancer and their correlation with IT-TMS treatment efficacy: a graph-theory analysis].

OBJECTIVE: To analyze the changes of brain small-world and node function network properties in patients with insomnia following radiotherapy for cervical cancer based on graph theory analysis and explore the correlation between functional networks and the clinical efficacy of individual-target transcranial magnetic stimulation (IT-TMS) for treatment of insomnia. METHODS: The resting state functional magnetic resonance imaging (rs-fMRI) data were collected from 30 patients with insomnia following radiotherapy for cervical cancer and 30 matched healthy individuals. All the patients received accelerated intelligent neuromodulation TMS therapy. Using graph theory analysis and GRETNA software, the functional connectivity matrices were constructed and the attribute features were extracted. The scores on the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) of the participants were collected before and after IT-TMS, and the correlation between improvement in insomnia and the functional network was investigated. RESULTS: The two groups matched for age, gender, and education level (P>0.05) showed significant differences in PSQI, ISI, SAS and SDS scores (P<0.05). Both groups showed attributes of the small-world network. Compared with the healthy individuals, the patients showed significantly decreased σ, EI, Cp and Lp (P<0.05) and increased Eg (P<0.05) at baseline, which, along with insomnia symptoms, were all improved after IT-TMS treatment. The patients showed reduced functional connections of the node network at follow-up compared with the baseline, and the low functional connectivity between the right insula and left superior frontal gyrus was correlated with the improvement of ISI scores. CONCLUSION: The patients with insomnia following radiotherapy for cervical cancer have impaired information integration ability of the brain network, IT-TMS can significantly improve insomnia symptoms by reducing the hyperconnectivity between the default mode network and the salience network.

Effect of mechanical ventilation guided by transpulmonary pressure in acute respiratory distress syndrome patients: a systematic review and meta-analysis of randomized control trials.

OBJECTIVE: This study aimed to investigate the effect of mechanical ventilation guided by transpulmonary pressure in patients diagnosed with acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Randomized control trials of ARDS patients that received mechanical ventilation guided by transpulmonary pressure vs. mechanical ventilation guided by traditional lung protective ventilation strategies in adults were retrieved by two reviewers independently from PubMed, EMBASE, The Cochrane Library, The China National Knowledge Infrastructure, and WanFang database before October 2022. The protocol has been registered on PROSPERO (CRD42022307816). The primary outcome was mortality. The secondary outcomes included mechanical ventilation days, oxygenation function and ventilation parameters, hemodynamics, and cytokines level. RESULTS: Thirteen articles (819 patients) were finally included through our search strategy. The total mortality (RR, 0.68; 95% CI, 0.54-0.85; p = 0.0006) and mechanical ventilation days (MD, -2.77; 95% CI, -4.60 - -0.94; p = 0.003) reduced when compared with the control group. Patients in the transpulmonary pressure group had higher oxygen index (MD, 40.74; 95% CI 9.81-71.68, p = 0.010) and lung compliance (MD, 7.98; 95% CI 4.55-11.41, p < 0.00001). Positive end-expiratory pressure (PEEP) was higher in the transpulmonary pressure group (MD, 5.47; 95% CI, 3.59 - 7.35; p < 0.00001). The Interlukin-6 (IL-6) level in the control group decreased obviously compared with that in the transpulmonary pressure group (SMD, -2.03; 95% CI, -3.50 - -0.56; p = 0.007). CONCLUSIONS: Mechanical ventilation guided by transpulmonary pressure tended to have a beneficial prognosis on ARDS patients. Oxygenation and lung mechanics parameters were also improved. The clinical effect of mechanical ventilation directed by transpulmonary pressure was superior to the traditional lung protective ventilation strategies in ARDS patients.

[Predictive value of low-density lipoprotein cholesterol/remnant cholesterol coordination on cardiovascular and cerebrovascular events in elderly patients with hypertension].

Objective: To explore the predictive value of serum low-density lipoprotein cholesterol/residual cholesterol (LDL-C/RC) coordination on major adverse cardiovascular events (MACE) in elderly hypertensive patients. Methods: This is a prospective cohort study. Elderly hypertensive patients hospitalized in Beijing Anzhen Hospital from June 2018 to June 2020 were prospectively enrolled. According to the coordination of baseline LDL-C/RC, patients were divided into four groups: low LDL-C and low RC (LDL-C<2.6 mmol/L, and RC<0.62 mmol/L), low LDL-C and high RC (LDL-C<2.6 mmol/L, and RC≥0.62 mmol/L), high LDL-C and low RC (LDL-C≥2.6 mmol/L, and RC<0.62 mmol/L), and high LDL-C and high RC (LDL-C≥2.6 mmol/L, and RC≥0.62 mmol/L). Patients were followed up until June 2022. The primary outcome was MACE, including non-fatal acute coronary syndrome, non-fatal acute heart failure, non-fatal stroke and death. Kaplan-Meier survival analysis was used to evaluate MACE among the four groups, and Cox regression analysis was performed to evaluate the related factors of MACE. Results: A total of 847 hypertensive patients were enrolled. There were 453 males (53.5%), mean age was (72.4±8.8) years. There were 207, 162, 263, 215 patients in the low LDL-C and low RC, low LDL-C and high RC, high LDL-C and low RC and high LDL-C and high RC group, respectively. During a median follow-up of 37 months, 196 patients (23.1%) had MACE, including 77 cases (9.1%) of ACS, 56 cases (6.6%) of acute heart failure, 34 cases (4.0%)of non-fatal stroke, 29 cases(3.4%) of all-cause mortality, and 16 cases (1.9%) of cardiovascular death. Risk of MACE of the four groups was significantly different (log-rank P<0.001). Compared with low LDL-C and low RC groups, high LDL-C and high RC groups had the highest incidence of MACE (HR=2.237, 95%CI 1.328-3.783, P=0.004), followed by low LDL-C and high RC groups (HR=1.745, 95%CI 1.220-2.527, P=0.003) and high LDL-C and low RC groups (HR=1.393, 95%CI1.048-1.774, P=0.022). In addition, the risk of nonfatal ACS among the four groups was also statistically significant (P=0.037), while the risk of nonfatal acute heart failure, nonfatal stroke, all-cause mortality and cardiovascular death were similar (all P>0.05). Multivariate Cox regression analysis showed that age (HR=1.271), duration of hypertension (HR=1.339), diabetes (HR=1.415), hyperlipidemia (HR=1.348), serum creatinine (HR=1.263), N-terminal pro-B-type natriuretic peptide (HR=1.316), LDL-C (HR=1.205), RC (HR=1.302), low LDL-C and high RC (HR=1.745), high LDL-C and low RC (HR=1.393), high LDL-C and high RC (HR=2.237) were independently associated with the occurrence of MACE. Conclusion: The coordination of LDL-C/RC affects the risk of MACE in elderly hypertensive patients, and the risk of MACE is the highest in patients with high LDL-C and high RC.

[A prospective study on the safety and efficacy of excimer laser coronary angioplasty for the treatment of degenerated great saphenous vein graft].

Objective: To explore the safety and efficacy of excimer laser coronary angioplasty (ELCA) for the treatment of degenerated great saphenous vein graft (SVG). Methods: This is a single-center, prospective, single-arm study. Patients, who were admitted to the Geriatric Cardiovascular Center of Beijing Anzhen Hospital from January 2022 to June 2022, were consecutively enrolled. Inclusion criteria were recurrent chest pain after coronary artery bypass surgery (CABG), and coronary angiography confirmed that the SVG stenosis was more than 70% but not completely occluded, and interventional treatment for SVG lesions was planned. Before balloon dilation and stent placement, ELCA was used to pretreat the lesions. Optical coherence tomography (OCT) examination was performed and postoperative index of microcirculation resistance (IMR) were assessed after stent implantation. The technique success rate and operation success rate were calculated. The technique success was defined as the successful passage of the ELCA system through the lesion. Operation success was defined as the successful placement of a stent at the lesion. The primary evaluation index of the study was IMR immediately after PCI. Secondary evaluation indexes included thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), minimal stent area and stent expansion measured by OCT after PCI, and procedural complications (Ⅳa myocardial infarction, no reflow, perforation). Results: A total of 19 patients aged (66.0±5.6) years were enrolled, including 18 males (94.7%). The age of SVG was 8 (6, 11) years. The length of the lesions was greater than 20 mm, and they were all SVG body lesions. The median stenosis degree was 95% (80%, 99%), and the length of the implanted stent was (41.7±16.3)mm. The operation time was 119 (101, 166) minutes, and the cumulative dose was 2 089 (1 378, 3 011)mGy. The diameter of the laser catheter was 1.4 mm, the maximum energy was 60 mJ, and the maximum frequency was 40 Hz. The technique success and the operation success rate were both 100% (19/19). The IMR after stent implantation was 29.22±5.95. The TIMI flow grade of patients after ELCA and stent implantation was significantly improved (all P>0.05), and the TIMI flow grade of all patients after stent implantation was Grade Ⅲ. The cTFC decreased significantly after ELCA (33.2±7.8) and after stent placement (22.8±7.1) than preoperative level (49.7±13.0) (both P<0.001). The minimum stent area was (5.53±1.36)mm2, and the stent expansion rate was (90.0±4.3)%. Perforation, no reflow, type Ⅳa myocardial infarction and other complications were not observed. However, postoperative high-sensitivity troponin level was significantly increased ((67.937±33.839)ng/L vs. (5.316±3.105)ng/L, P<0.001). Conclusion: ELCA is safe and effective in the treatment of SVG lesions and could improve microcirculation and ensure full expansion of stent.

Analysis of growth performance and carcass and meat quality of different crossbreeds of Cherry Valley duck.

1. Duck breeding and production are facing great opportunities in China, as the market for small-sized high-quality duck is rapidly expanding. Therefore, breeding the most suitable genetic stock has become an important goal.2. This study assessed body and carcass weight, slaughter rate and meat quality of offspring of three cross combinations; Cherry Valley duck (CV♂) × Small-sized Pekin duck (PK♀), CV♂×Taiwan white duck (TW♀), CV♂×Putian white duck (PT♀) and the corresponding pure lines at 56 d of age. These 420 ducks were raised in seven separate groups (10 pens/group, 3♂+3♀/pen).3. Body and carcass weights were significantly lower in the three cross combinations than CV ducks (P = 0.042 and P = 0.012). Abdominal fat was lowest in CV♂×PK♀, whereas the breast and the leg muscle weights were significantly higher in CV♂×PK♀ compared to CV♂×TW♀ and CV♂×PT♀ (P = 0.018 and P = 0.023). No difference was observed in the visceral tissues among the three cross combinations or compared to CV ducks.4. The performance indicators suggested that CV♂×PK♀, CV♂×TW♀ and CV♂×PT♀ cross combinations are best suited for segmented duck meat, featured duck meat and whole-duck processing, respectively.

[Research progress in anti-reflux reconstructions and mechanism after proximal gastrectomy].

The electrophysiological activity of the gastrointestinal tract and the mechanical anti-reflux structure of the gastroesophageal junction are the basis of the anti-reflux function of the stomach. Proximal gastrectomy destroys the mechanical structure and normal electrophysiological channels of the anti-reflux. Therefore, the residual gastric function is disordered. Moreover, gastroesophageal reflux is one of the most serious complications. The emergence of various types of anti-reflux surgery through the mechanism of reconstructing mechanical anti-reflux barrier and establishing buffer zone, and the preservation of, the pacing area and vagus nerve of the stomach, the continuity of the jejunal bowel, the original gastroenteric electrophysiological activity of the gastrointestinal tract, and the physiological function of the pyloric sphincter, are all important measures for gastric conservative operations. There are many types of reconstructive approaches after proximal gastrectomy. The design based on the anti-reflux mechanism and the functional reconstruction of mechanical barrier, and the protection of gastrointestinal electrophysiological activities are important considerations for the selected of reconstructive approaches after proximal gastrectomy. In clinical practice, we should consider the principle of individualization and the safety of radical resection of tumor to select a rational reconstructive approaches after proximal gastrectomy.

[Depression status of elderly patients with metabolic syndrome in three provinces of China].

Objective: To understand the depression status and its influencing factors in elderly patients with MS in China and to explore the correlation between various components of elderly MS and depression. Methods: This study is based on the "Prevention and Intervention of Key Diseases in Elderly" project. We used a multi-stage stratified cluster random sampling method to complete 16 199 elderly aged 60 years and above in 16 counties (districts) in Liaoning, Henan, and Guangdong Provinces in 2019, excluding 1 001 missing variables. Finally, 15 198 valid samples were included for analysis. The respondents' MS disease was obtained through questionnaires and physical examinations, and the respondents' depression status within the past half month was assessed using the PHQ-9 Depression Screening Scale. The correlation between elderly MS and its components and depression and its influencing factors were analyzed by logistic regression. Results: A total of 15 198 elderly aged 60 years and above were included in this study, with the prevalence of MS at 10.84% and the detection rate of depressive symptoms in MS patients at 25.49%. The detection rates of depressive symptoms in patients with 0, 1, 2, 3, and 4 MS abnormal group scores were 14.56%, 15.17%, 18.01%, 25.21%, and 26.65%, respectively. The number of abnormal components of MS was positively correlated with the detection rate of depressive symptoms, and the difference between groups was statistically significant (P<0.05). The risk of depression symptoms in patients with MS, overweight/obesity, hypertension, diabetes, and dyslipidemia was 1.73 times (OR=1.73, 95%CI:1.51-1.97), 1.13 times (OR=1.13, 95%CI:1.03-1.24), 1.25 times (OR=1.25, 95%CI:1.14-1.38), 1.41 times (OR=1.41, 95%CI:1.24-1.60), 1.81 times (OR=1.81,95%CI:1.61-2.04), respectively, more than those without the disease. Multivariate logistic regression analysis showed that the detection rate of depressive symptoms in patients with sleep disorders was higher than that with normal sleep (OR=4.89, 95%CI: 3.79-6.32). The detection rate of depressive symptoms in patients with cognitive dysfunction was 2.12 times higher than that in the average population (OR=2.12, 95%CI: 1.56-2.89). The detection rate of depressive symptoms in patients with impaired instrumental activities of daily living (IADL) was 2.31 times (OR=2.31, 95%CI: 1.64-3.26) higher than that in the average population. Tea drinking (OR=0.73, 95%CI: 0.54-0.98) and physical exercise (OR=0.67, 95%CI: 0.49-0.90) seemed to be protective factors for depression in elderly MS patients (P<0.05). Conclusions: Older patients with MS and its component abnormalities have a higher risk of depression than the average population. Sleep disorders, cognitive impairment, and IADL impairment are important influencing factors for depression in elderly MS patients, while tea drinking and physical exercise may help to reduce the risk of the disease.

[Establishment and digital simulation of upper airway in patients with adenoid hypertrophy].

Objective: To analyze the flow field characteristics of the upper airway in patients with different adenoid hypertrophy using computational fluid dynamics (CFD). Methods: From November 2020 to November 2021, the cone-beam CT (CBCT) data of 4 patients [2 males and 2 females,age range 5-7 years, mean (6.0±1.2) years] with adenoid hypertrophy who were hospitalized in the Department of Orthodontics and the Department of Otolaryngology at Hebei Eye Hospital were selected. The degree of adenoid hypertrophy in the 4 patients was divided into normal S1 (A/N<0.6), mild hypertrophy S2 (0.6≤A/N<0.7), moderate hypertrophy S3 (0.7≤A/N<0.9) and severe hypertrophy S4 (A/N≥0.9) according to the ratio of adenoid thickness to the width of nasopharyngeal cavity (A/N). The CFD model of the upper airway was established using ANSYS 2019 R1 software, and the internal flow field of the CFD model was numerically simulated. Eight sections were selected as observation and measurement planes for flow field information. Relevant flow field information includes airflow distribution, velocity variation, and pressure variation. Results: In the S1 model, the maximum pressure difference occurred in the 4th and 5th observation planes (ΔP=27.98). The lowest pressures and the maximum flow rates of S2 and S3 were located in the 6th observation plane. The airflow in S1 and S2 models completely passed through the nasal cavity. In the S3 model, the mouth-to-nasal airflow ratio was close to 2∶1. In S4 model, the airflow completely passed through the mouth; in the S1 and S2 models, hard palates were subjected to a downward positive pressure with a pressure difference of 38.34 and 23.31 Pa, respectively. The hard palates in S3 and S4 models were subjected to a downward negative pressure with a pressure difference of -2.95 and -21.81 Pa, respectively. Conclusions: The CFD model can objectively and quantitatively describe the upper airway airflow field information in patients with adenoid hypertrophy. With the increasing degree of adenoid hypertrophy, the nasal ventilation volume gradually decreased, whereas the oral space ventilation volume gradually increased, and the pressure difference between the upper and lower surfaces of the palate gradually decreased until the pressure became negative.

[Eriocitrin suppresses proliferation and migration of hepatocellular carcinoma SMMC-7721 cells by promoting ROS production and activating the MAPK pathway].

OBJECTIVE: To investigate the role of the ROS/MAPK signaling axis in mediating the inhibitory effect of eriocitrin on proliferation and migration of hepatocellular carcinoma SMMC-7721 cells. METHODS: SMMC-7721 cells were treated with different concentrations of eriocitrin for 24 h, and the changes in cell viability were detected with CCK-8 assay. The migration and invasion abilities of the treated cells were evaluated using Transwell and scratch healing assays, the cell proliferation was assessed with colony-forming assay, and changes in nuclear morphology were observed with DAPI staining. Western blotting was performed to examine the changes in the expressions of E-cadherin, N-cadherin, MMP-2, MMP-9, PARP, Pro-caspase 3, pJNK, p-P38, and p-ERK. The effect of eriocitrin on PARP cleavage in SMMC-7721 cells pretreated with ERK, JNK and P38 inhibitors (U0126, SB203580 and SP600125, respectively) was detected using Western blotting. The effect of treatment with Nacetyl-cysteine (NAC, 30 µmol/L) and eriocitrin (100, 200, and 300 µg/mL), alone or in combination, on reactive oxygen species (ROS) levels in the cells was examined using a DCFH-DA fluorescent probe. RESULTS: Eriocitrin below 50 µg/mL did not produce significant effect on the viability of SMMC-7721 cells (P>0.05). Treatment with eriocitrin significantly inhibited scratch healing, migration, and colony formation of the cells (P < 0.01), reduced the protein expressions of N-cadherin, MMP-2, and MMP-9 (P < 0.01), and up-regulated E-cadherin protein expression (P < 0.05). Eriocitrin-treated SMMC-7721 cells showed obvious apoptotic morphologies with decreased Procaspase 3 expression and increased PARP cleavage (P < 0.01) and phosphorylation levels of JNK, P38, and ERK (P < 0.01); Eriocitrin-induced PAPR cleavage was obviously enhanced by U0126 and SB203580 but attenuated by SP600125. Treatment with 300 µg/mL eriocitrin for 30 min significantly increased ROS level in the cells, and this effect was obviously suppressed by NAC. CONCLUSION: Eriocitrin can suppress the proliferation and migration and promote apoptosis of hepatocellular carcinoma SMMC-7721 cells by promoting ROS production and activating the MAPKs signaling pathway.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Depression status and its influencing factors among the elderly aged 60 years and above in three provinces of China].

Objective: The survey learned about the current status of depression in community's elderly aged 60 years and older and explored its influencing factors. Methods: Respondents from the "Prevention and Intervention of Key Diseases in the Elderly" project used a multi-stage stratified cluster random sampling method to complete the depression screening of 14 335 ≥60-year-old elderly people in 16 counties and districts Liaoning, Henan, and Guangdong provinces in 2019. Through the questionnaire survey on the demographic characteristics of the subjects, whether they live with their families or interact with neighbors, daily exercise, cognitive function, and activity of daily living (ADL), the PHQ-9 depression screening scale was used to assess the depression status of the elderly in the last fortnight. Binary logistic regression was used to analyze the influencing factors of depression in the elderly. Results: The prevalence of depressive symptoms among the elderly in Liaoning province, Henan province, and Guangdong province was 15.45%, and those in the three provinces were 18.17%, 18.87% and 9.93%, respectively. There were differences between urban and rural areas in the detection rate of depressive symptoms among the elderly in different regions, among which Henan: 17.09% vs. 20.61%; Guangdong province: 7.99% vs. 11.03%, the differences were statistically significant (P<0.05). The results of multivariate logistic regression analysis showed that the detection rate of depressive symptoms in older women was higher than that in men (OR=1.76, 95%CI: 1.58-1.96), in those divorced or separated (OR=2.08, 95%CI: 1.01-4.30), with cognitive dysfunction (OR=1.78, 95%CI: 1.59-1.98) or impaired essential ability of daily living (BADL) (OR=1.74, 95%CI: 1.23-2.46). The impaired instrumental ability of daily living (IADL) (OR=2.23, 95%CI: 1.97-2.54) was a risk factor for depression in the elderly (P<0.05), and the impact of IADL impairment on depression in the elderly was higher than that of BADL impairment (2.23 vs. 1.74). Results also showed that factors as: 80 years old and above (OR=0.82, 95%CI: 0.68-0.99), living with family members (OR=0.67, 95%CI: 0.57-0.80), interacting with neighbors (OR=0.86, 95%CI: 0.76-0.98), exercise multiple times per week (OR=0.82, 95%CI: 0.69-0.96), and exercise almost every day (OR=0.63, 95%CI: 0.56-0.70) were protective for depression in the elderly (P<0.05). Conclusions: The detection rate of depressive symptoms in the elderly aged 60 and above in the community is relatively high in China. Gender, marital status, social interaction, physical exercise, cognitive function, and ADL are all influencing factors of depression in the elderly. The elderly health care sector should carry out psychological prevention and intervention of critical populations.

[Progress in research and development of soft tissue three-dimensional bioprinting and its supporting equipment].

As a cutting-edge technology of tissue engineering, three-dimensional bioprinting can accurately fabricate biomimetic tissue, which has made great progress in the field of hard tissue printing such as bones and teeth. Meanwhile, the research on soft tissue bioprinting is also developing rapidly. This article mainly discussed the development progress in various bioprinting technologies and supporting equipment including printing software, printing hardware, supporting consumables, and bioreactors for soft tissue three-dimensional bioprinting, and made a prospect for the future research and development direction of soft tissue three-dimensional bioprinting.

[Research advances on the application of natural and recombinant collagen in wound repair].

Collagen is a macromolecular protein constituting the extracellular matrix of animal connective tissue, which has been widely used and developed in fields of biomedicine, tissue engineering, food, and cosmetics. Due to its advantages such as abundant sources and good biocompatibility, low immunogenicity, and degradability, collagen can be used as a dressing or tissue engineering scaffold for wound repair. According to the source of materials, collagen can be divided into natural collagen and recombinant collagen. Natural collagen is mainly extracted directly from mammals and fish; recombinant collagen is obtained based on genetic engineering technology, and its sources include recombinant expression systems of microorganisms, animals, and plants. This paper summarizes the sources of collagen, and the roles, advantages, and disadvantages of different sources of collagen in wound repair, the particularity and superiority of collagen combined with three-dimensional printing technology in wound repair, the impact of market norms of China's collagen industry on the field of wound repair, and explains the precautions for the development of collagen-related products, aiming to provide new ideas for selecting a suitable source of collagen for wound repair.

Long-term use of Lacticaseibacillus paracasei N1115 from early life alleviates high-fat-diet-induced obesity and dysmetabolism in mice.

Obesity has become one of the most serious public health problems worldwide, and an increasing number of studies indicate that the gut microbiota can affect host metabolism. Therefore, the present study was conducted to evaluate whether long-term use of probiotics can alleviate host obesity and metabolism by altering gut microbiota. The high-fat diet (HFD) starting from weaned period led to higher levels of visceral fat and a significantly heavier liver in male mice. Moreover, HFD resulted in disorders of glucose and lipid metabolism, changes in insulin-resistance indices (IR), and an increase in serum insulin and leptin in mice. Of note, 15 weeks use of Lacticaseibacillus paracasei N1115 decreased visceral fat, liver weight, serum levels of insulin and leptin, and IR and alleviated lipid dysmetabolism. HFD resulted in a significant increase in the relative abundance of Bilophila, Lachnoclostridium, and Blautia and may decrease the faecal short-chain fatty acid (SCFA) levels in mice; in turn, treatment with the potential probiotic strain L. paracasei N1115 protected mice from these negative effects. HFD significant impaired the physiology of the host especially in male mice and dramatically changed the composition of host gut microbiota. However, the use of potential probiotic strain, such as L. paracasei N1115, may prevent these impairments due to HFD via effecting the host gut microbiota and SCFA.