Objective To investigate the influencing factors associated with the comorbidity of inflammatory bowel disease (IBD) and depression. Methods A case-control study was conducted based on the ^“Healthcare Big Data Platform^” of a tertiary class-A comprehensive hospital in Shandong Province. IBD comorbid with depression was served as the case group and IBD without depression was served as the control group. Propensity score matching (PSM) was performed by matching the case group with the control group in a ratio of 1:2 according to the age and gender of the patients. Conditional logistic regression model was used to explore the influencing factors associated with the comorbidity of IBD and depression. Results A total of 405 patients with IBD were enrolled in this study, including 270 patients without depression and 135 patients comorbid with depression. The results of conditional logistic regression showed that the use of immunosuppressants (OR=2.84, 95% CI: 1.00-8.07) and glucocorticoids (OR=2.05, 95% CI: 1.17-3.58), dementia (OR=5.20, 95% CI:1.59-17.05), cardiovascular disease (OR=3.58, 95% CI: 1.84-6.98) and cancer (OR=2.63, 95% CI: 1.16-5.95) were associated with the comorbidity of depression and IBD. Conclusion Attention should be paid to the use of immunosuppressants and glucocorticoids in the population of IBD comorbid with depression, and the coexistence of physical diseases such as dementia, cardiovascular disease and cancer. Early prevention and targeted treatment measures should be taken for high-risk populations to reduce their risk of depression and improve their quality of life and health.

Objective:To evaluate the effect of propofol on parvalbumin (PV) neurons in the medical prefrontal cortex(mPFC)of rats with social behavior disorders induced by chronic sleep deprivation.Methods:Forty-two SPF male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=14 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (group CSD+ Pro). Sleep deprivation model was established by the modified multiple platform method, the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00), and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days. Propofol 40 mg/kg was intraperitoneally injected for 28 consecutive days after sleep deprivation in CSD+ Pro group. While the equal volume of 10% fat emulsion was given in Con and CSD+ NS groups. After the end of sleep deprivation, a three-box social experiment was used to detect the social behavior of rats, and the number of the PV positive cells and density of the perineuronal network (PNN) in the mPFC area were measured by immunofluorescence. Results:Compared with group Con, the pertentage of rapid eye movement sleep and sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly decreased, and the number of the PV positive cells and density of PNN in the mPFC area were decreased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly increased, the number of the PV positive cells and density of PNN in the mPFC area were increased( P<0.05), and no significant change was found in the percentage of the rapid eye movement sleep in group CSD+ Pro. Conclusions:Propofol probably increases the number and function of PV neurons in the mPFC and ameliorates sleep deprivation-induced social behavior disorders in sleep-deprived rats.

Objective: To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi (HHRY) pills for endometriosis-associated dysmenorrhea. Methods: This study constitutes a multicenter, randomized, double-blind, placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period. A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio. The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale (VAS) scores and quality of life, whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain, duration of pain episodes (in days), frequency and quantity of the consumption of ibuprofen sustained-release capsules (or other non-steroidal anti-inflammatory drugs), and days off work/study for staff/student due to dysmenorrhea, ovarian cyst, and/or pelvic nodule size. The safety was monitored throughout the treatment period. All the analyses were based on the intention-to-treat principle. For continuous outcomes, simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups, with categorical data expressed as the number and percentage of occurrences. Differences were compared using the chi-square test or Fisher's exact test. The predefined analysis was adjusted for concomitant treatment, a variable considered to be associated with outcomes but unaffected by treatment allocation. Estimates of treatment effects were reported with 95% confidence intervals. Two-tailed P values ≤ .05 were considered statistically significant. Conclusion Positive results from this trial, upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Objective:To analyze the changing trends in maternal mortality ratios (MMRs) and the main cause-specific MMRs in China from 2010 to 2020, evaluate the association between MMRs and pregnancy healthcare and predict the MMRs for the next five years.Methods:Data on MMRs, the main cause-specific MMRs, and maternal healthcare in China from 2010 to 2020 were collected from China Health Statistical Yearbook. Estimated annual percent changes (EAPCs) were used to analyze the trends in MMRs and the main cause-specific MMRs in China. Average growth rate was used to describe the trend of perinatal healthcare indicators, and spearman rank correlation was used to analyze the correlation between MMRs and perinatal healthcare indicators. GM (1,1) model was established to predict the MMRs for the following five years. Results:(1) From 2010 to 2020, the EAPCs were－5.16%,－6.24%, and－4.28%, respectively, indicating downward trends in MMRs in the whole nation, urban and rural areas ( t=－0.98,－12.42 and－8.96, all P<0.001). (2) From 2010 to 2020, the main cause-specific MMRs in China from obstetric hemorrhage, hypertension during pregnancy, amniotic fluid embolism, and liver disease were all in downward trends ( t=－12.42,－5.44,－3.98 and－3.63, all P<0.001). Except for the MMR from hypertension during pregnancy in urban areas (average growth rate =0.51%), all main cause-specific MMRs in both urban and rural areas decreased significantly, especially the MMRs from hepatopathy in urban and rural areas (average growth rate=－10.40% and－13.96%). (3) The nation wide MMR was negatively correlated with maternal system management rate ( r s=－0.80, P=0.003), prenatal examination rate ( r s=－0.97, P<0.001), postpartum visit rate ( r s=－0.82, P=0.002) and hospital delivery rate ( r s=－0.98, P<0.001). Negative correlations were also found between the MMR and hospital delivery rate in both urban ( r s=－0.82, P=0.002) and rural areas ( r s=－0.95, P<0.001). (4) The GM (1, 1) models for forecasting MMRs in the whole nation, urban and rural areas were established with an accuracy of level 1. The MMR was predicted to show a downward trend in the following five years. The MMRs in China were 15.86/100 000 in 2021 and 15.13/100 000 in 2022 through prediction, similar to the 16.1/100 000 and 15.7/100 000 as announced by the government. Conclusions:The overall MMR in China shows a downward trend, and it dropped faster in urban areas than the rural areas. In addition, it is predicted that the MMR will continue to decline in the following five years, but the gap between urban and rural areas will remain.

Background The pathogenesis of silicosis is complex and treatment methods are limited. SiO₂-induced increase of transforming growth factor-β1 (TGF-β1) can activate fibroblasts to promote collagen deposition, ultimately leading to fibrosis. Previous studies have confirmed that lipid metabolism plays an important role in the progression of silicosis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) mediates mitochondrial dysfunction and lipid metabolism pathways in diabetic models, but its role in silicosis has not been elucidated. Objective To investigate the effect of PGC1α on lipid metabolism disorder of macrophages induced by SiO₂ and its effect on the progression of silicosis fibrosis. Methods (1) Macrophages were divided into four groups by transfecting and silencing PGC1α and its control sequence in macrophages and followed by SiO₂ stimulation: negative control group (transfected with si-NC for 48 h), si-PGC1α group (transfected with si-PGC1α for 48 h), SiO₂ stimulation group (stimulated with 50 μg·mL⁻¹ SiO₂ for 36 h after transfection with si-NC for 48 h), and si-PGC1α+SiO₂ group (stimulated with 50 μg·mL⁻¹ SiO₂ for 36 h after transfection with si-PGC1α for 48 h). Western blot and cell immunofluorescence were used to test PGC1α expression, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and total cholesterol (TC) and free cholesterol (FC) kits were used to test lipid accumulation, and the Oroboros2k-Oxygraph respiratory test system (O2K) was used to assess the effects of PGC1α on mitochondrial respiratory chain. ELISA kits were used to test TGF-β1 expressed in the macrophage supernatant. (2) Lung fibroblasts were divided into the same four groups as above, and stimulated with the supernatant of macrophages in the above groups. The expression of collagen Ι (COL Ι), E-cadherin (Eca), and fibronectin (FN) were detected by cell immunofluorescence and Western blot to further evaluate the effect of silencing PGC1α on fibrosis. Results The protein expression level of PGC1α stimulated by SiO₂ was decreased, and the relative expression level of PGC1α was 0.78 times that of the control group (P<0.05). After transfection with si-PGC1α, the expression of PGC1α was decreased, and the relative protein expression level of the si-PGC1α group was 0.86 times that of the control group (P<0.05). Compared with the SiO₂ stimulation group, the staining area of BODIPY 493/503 in the si-PGC1α+SiO₂ group was enhanced, and the cholesterol-related indexes [TC, FC and cholesterol ester (CE)] were increased to 1.38, 1.10, and 2.26 times those in the SiO₂ stimulation group (P<0.05). The activity of mitochondrial complex Ι was decreased, and the level of complex Ι in the si-PGC1α+SiO₂ group was 0.63 times that in the SiO₂ stimulation group (P<0.05). The secretion of TGF-β1 by macrophages increased, and the level of TGF-β1 in the si-PGC1α+SiO₂ group was 1.15 times that of the SiO₂ stimulation group (P<0.05). In addition, after stimulation of primary lung fibroblasts with macrophage supernatant, silencing PGC1α increased the expression levels of COL Ι and FN, while decreased the expression of Eca. The protein levels of COL Ι, FN, and Eca in the si-PGC1α+SiO₂ group were 1.39, 1.18, and 0.82 times those in the SiO₂ stimulation group, respectively (P<0.05). Conclusion Silencing PGC1α exacerbates SiO₂-induced lipid metabolism disorder, inhibits mitochondrial respiratory chain, and aggravates the fibrosis induced by SiO₂, suggesting that PGC1α may participate silicosis fibrosis by regulating mitochondrial respiratory chain and lipid metabolic disorder induced by SiO₂.

Tumor immunotherapy has become the main treatment method for cancer after surgery, radiotherapy and chemotherapy. With the in-depth study of tumor immunology, cell biology and molecular technology, the tumor microenvironment was found to be immunosuppressive, and tumor development and metastasis are closely related to it. Tumor immunotherapy uses the body’s own immune system to kill tumor cells. At present, there are mainly mainstream tumor immunotherapy methods, namely monoclonal antibody therapy, immune checkpoint inhibitor therapy, immunocell therapy, and tumor vaccines. In this paper, the advantages and limitations of these four immunotherapies were mainly discussed, and the current status of their marketing and clinical research was also reviewed.

Objective:To explore the relevance between secondary retroperitoneal infection, as well as the outcomes, and the approach of intensive care unit (ICU) admission for the patients suffered from acute pancreatitis.Methods:Patients with acute pancreatitis admitted to the ICU of the Second Affiliated Hospital of Anhui Medical University from January 2013 to July 2022 were retrospectively analyzed. According to ICU admission approaches, the patients were divided into the emergency group (first admission or transferred from the emergency department) and the delayed group (transferred from the general wards due to disease evolution). Patients were also divided into retroperitoneal infection group and non-retroperitoneal infection group according to whether retroperitoneal infection was accompanied. Patients' baseline data including gender, age, underlying diseases, laboratory test indicators, acute physiology and chronic health evaluationⅡ score (APACHEⅡ), sequential organ failure assessment (SOFA), computed tomography severity index (CTSI), bedside index of severity in acute pancreatitis (BISAP), and acute complications were collected. Univariate and multivariate logistic regression was used to analyze the risk factors of retroperitoneal infection in patients with acute pancreatitis.Results:A total of 271 patients with acute pancreatitis were enrolled, including 95 cases in the emergency group and 176 cases in the delayed group. The cohort included 71 cases with and 200 cases without retroperitoneal infection development. The incidence of retroperitoneal infection and the 30-day mortality of patients in the delayed group, which was observed with a significantly longer ICU stay (days), [(15.4±21.3) vs. (8.6±10.8), P<0.05], were significantly higher than those in the emergency group [retroperitoneal infection incidence rate: 31.82% (56/176) vs.15.79%(15/95), 30-day mortality: 13.64%(24/176) vs. 4.21%(4/95), both P<0.05]. Univariate Logistic analysis showed significant differences in diabetes, APACHEⅡ, SOFA, CTSI and BISAP score, urea nitrogen, creatinine, blood calcium, D-D dimer, peritoneal puncture catheter drainage and ICU transferred from general wards due to disease evolution between the retroperitoneal infection group and the non-retroperitoneal infection group. Multivariate Logistic regression analysis showed that diabetes, SOFA score, CTSI score, peritoneal puncture catheter drainage and transfered from general wards to ICU due to disease evolution were independent risk factor for retroperitoneal infection in acute pancreatitis patients[odds ratio were 3.379, 1.150, 1.358, 3.855, 2.285, respectively]. Conclusions:Acute pancreatitis patients in ICU transferred from general wards are more likely to develop retroperitoneal infection, and have a higher risk of mortality and a longer ICU stay. Delayed admission to ICU, diabetes, SOFA score, CTSI score and peritoneal puncture catheter drainage are independent risk factors for retroperitoneal infection in patients with acute pancreatitis.

Objective:To investigate the effect of ultrasound-guided lumbar quadratus muscle plane block combined with general anesthesia on the analgesic effect during and after laparoscopic colon cancer radical surgery in elderly patients.Methods:A prospective study was conducted on 61 elderly patients who underwent radical colon cancer surgery at the Changsha Central Hospital Affiliated to South China University from May 2022 to February 2023, with American Society of Anesthesiologist (ASA) grades Ⅱ to Ⅲ. They were randomly divided into SA and GA groups using a random number table method, with 31 patients in the SA group and 30 patients in the GA group. The SA group received ultrasound-guided plane block of the upper lumbar quadratus muscle in the arcuate ligament combined with general anesthesia, while the GA group received simple general anesthesia. Record the mean artery pressure (MAP) and heart rate (HR) of two groups of patients at the time of entering the operating room (T 0), 5 minutes before skin incision (T 1), at skin incision (T 2), 30 minutes after surgery (T 3), at surgery end (T 4), and during anesthesia resuscitation and extubation (T 5); The Visual Analogue Scale (VAS) of two groups of patients at T 5, upon returning to the ward (T 6), 6 hours (T 7), 12 hours (T 8), 24 hours (T 9), and 48 hours (T 10) after surgery were recorded; The dosage of sufentanil, remifentanil, and propofol used during surgery, anesthesia recovery time, total number of analgesic pump presses within 48 hours after surgery, Lovett muscle strength score, early postoperative recovery, and adverse reactions within 48 hours after surgery were also recorded. Resultsl:The MAP and HR of the SA group were lower than those of the GA group at T 1-5 (all P<0.05); The VAS score of the SA group was lower than that of the GA group at T 5-10 (all P<0.05); The intraoperative dosage of propofol, remifentanil, and sufentanil in the SA group was lower than that in the GA group (all P<0.05); The anesthesia recovery time and first time out of bed in the SA group were earlier than those in the GA group (all P<0.05); The total number of times the analgesic pump was pressed within 48 hours after surgery was less than that of the GA group ( P<0.05); The incidence of nausea and vomiting within 48 hours after surgery in the SA group was lower than that in the GA group ( P<0.05). There was no statistically significant difference in postoperative Lovett muscle strength score, hospital stay, and dizziness incidence between the two groups of patients (all P>0.05). Conclusions:Ultrasound-guided lumbar quadratus muscle plane block on the arcuate ligament can significantly reduce the dosage of intraoperative general anesthesia drugs and postoperative analgesics in elderly patients undergoing laparoscopic colon cancer surgery, reduce postoperative pain scores, effectively alleviate postoperative pain, and thus advance the patient′s first time out of bed activity, reduce postoperative complications, and promote rapid recovery.

Prediction of the interactions between small molecules and their targets play important roles in various applications of drug development, such as lead discovery, drug repurposing and elucidation of potential drug side effects. Therefore, a variety of machine learning-based models have been developed to predict these interactions. In this study, a model called auxiliary multi-task graph isomorphism network with uncertainty weighting (AMGU) was developed to predict the inhibitory activities of small molecules against 204 different kinases based on the multi-task Graph Isomorphism Network (MT-GIN) with the auxiliary learning and uncertainty weighting strategy. The calculation results illustrate that the AMGU model outperformed the descriptor-based models and state-of-the-art graph neural networks (GNN) models on the internal test set. Furthermore, it also exhibited much better performance on two external test sets, suggesting that the AMGU model has enhanced generalizability due to its great transfer learning capacity. Then, a naïve model-agnostic interpretable method for GNN called edges masking was devised to explain the underlying predictive mechanisms, and the consistency of the interpretability results for 5 typical epidermal growth factor receptor (EGFR) inhibitors with their structure‒activity relationships could be observed. Finally, a free online web server called KIP was developed to predict the kinome-wide polypharmacology effects of small molecules (http://cadd.zju.edu.cn/kip).

Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.