ObjectiveQi deficiency and phlegm dampness syndrome is a common type of clinical traditional Chinese medicine（TCM） syndrome. However， there is no standard， scientific， and accurate report on the construction of animal models of Qi deficiency and phlegm dampness syndrome. This study aims to construct a mouse model of Qi deficiency and phlegm dampness syndrome by using a multi-factor composite modeling method and to evaluate the model. MethodsTwenty-one C57BL/6 mice were randomly divided into three groups with seven mice in each group， which were the normal group， model group， and Shenling Baizhusan （SLBZ） group. The control group was fed with ordinary diet and kept in a normal environment. The model group and SLBZ group were fed with a high-fat diet in a high-humidity environment. Swimming with heavy weights until exhaustion and gavage with cold water or lard were used to establish the mouse model of Qi deficiency and phlegm dampness syndrome. In order to test the syndrome by prescription， mice in the SLBZ group were treated with SLBZ for 14 days after model construction. The exhaustive swimming time， body weight， serum lipid levels， tongue changes， "Qi deficiency and phlegm dampness" assessment scale score， and cecal index of mice in each group were measured. The feces of each group of mice were sent for metagenomics and metabolome sequencing， and the changes in intestinal flora and metabolites were analyzed. ResultsAfter the modeling of Qi deficiency and phlegm dampness syndrome， the exhaustive swimming time of mice was obviously shortened （P<0.01）. The serum total cholesterol， low density lipoprotein cholesterol， and non-high density lipoprotein cholesterol of mice were significantly increased （all P<0.01）. The tongue of mice was significantly different from that of the normal group， and the score of the assessment scale was significantly higher than that of the control group （P<0.01）. Cecal index decreased significantly （P<0.01）. The serum lipid level， tongue image， assessment scale score， and cecal index were reversed in the SLBZ group. Metagenomic and metabolome sequencing results showed that intestinal flora and fecal metabolites were significantly changed in mice with Qi deficiency and phlegm dampness syndrome. Akkermansia_muciniphila， Faecalibaculum_rodentium， Eubacterium_plexicaudatum， Eubacterium sp 14_2， Candida glabrata， Romboutsia_ilealis， Turicibacter sp TS3， and other bacteria had significant changes， and the expressions of intestinal metabolites such as chenodeoxycholic acid， choline， L-phenylalanine betaine， and 2-phenylbutyric acid were significantly changed. Related metabolic pathways such as linoleic acid metabolism， primary bile acid biosynthesis， lysine degradation， arginine biosynthesis， and alpha-linolenic acid metabolism were affected. ConclusionThe Qi deficiency and phlegm dampness model of mice can be constructed by the multi-factor composite modeling method of high-fat diet feeding， high-humidity environment feeding， exhaustive swimming with heavy weight， and intragastric administration with cold water or lard. The blood lipid level， tongue change， score of "Qi deficiency and phlegm dampness assessment scale"， cecal index， and changes in related intestinal flora and metabolites of mice can be used as key indicators for model evaluation.

Objective: To investigate the current status of emotional and behavioral problems among preschool children in Hefei, and to explore their association with the family rearing environment, providing scientific evidence for improving the family rearing environment and promoting children s mental health. Methods: From March to May 2023, a stratified cluster sampling method was applied to select 1 893 preschool children from five kindergartens in Hefei. Data on children s emotional and behavioral problems and family rearing environment were collected through electronic questionnaires. The Strengths and Difficulties Questionnaire (Parent Version) was employed to assess children s emotional and behavioral problems. Binary Logistic regression was conducted to analyze their association with family rearing environment. Results: Among preschool children, the prevalence rates of emotional symptoms, conducts, hyperactivity/inattention, peer relationship difficulties, and prosocial behavior were 9.7% (184 cases), 37.7% (713 cases), 16.7% (316 cases), 48.5% (918 cases), and 17.5% (332 cases), respectively. The abnormal detection rate of total difficulties score was 18.3% (346 cases). Binary Logistic regression analysis showed that higher maternal education level (postgraduate degree), parental daily interaction time ≥1 h, daily outdoor activity time for children ≥2 h, consistent family rearing attitudes, and nightly sleep duration for children ≥8 h were associated with lower abnormal risks of total difficulties score in preschool children [ OR(95%CI )=0.48(0.24-0.95), 0.66(0.49-0.90), 0.65(0.48-0.87), 0.39(0.29-0.52), 0.71(0.51-0.99)，all P < 0.05 ]. Conclusion The abnormal detection rates of emotional and behavioral problems among preschool children in Hefei are at moderate levels, and family rearing environment is related to children s emotional and behavioral problems.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective : To investigate the role of endoplasmic reticulum stress in the occurrence and development of fatty liver induced by high fat. Methods : In the high-fat Drosophila model, the high-fat group was fed with high-fat medium, while the control group was fed with normal medium; in the mouse fatty liver model, the high-fat group was fed with high-fat diet, and the control group was fed with normal diet; in the HepG2 cell steatosis model, the high-fat group was induced by palmitic acid(PA), and the control group was cultured with DMEM. The fat body size of the third instar larvae of Drosophila melanogaster was photographed. Steatosis in mice liver and HepG2 cells was observed by H&E and Oil Red staining. The expression levels of ATF6, Bip and CHOP in the third instar larvae, liver tissues of mice and HepG2 cells were analyzed by quantitative real-time polymerase chain reaction(qPCR) and Western blot. Results : In Drosophila model, fat body and fat storage were obviously increased in high fat fed flies when compared with control group. The formation of liver fat droplets and cells vacuolation were confirmed by H&E and Oil Red staining in mice livers fed with high fat and HepG2 cells with palmitic acid treatment. The expression levels of ATF6, Bip and CHOP were significantly increased in third instar larvae and mice livers fed with high fat and palmitic acid treated HepG2 cells with palmitic acid treatment. Conclusion High fat may induce the occurrence and development of hepatic steatosis by activating endoplasmic reticulum stress.

Objective: To investigate the effect of loss of function of lanosterol synthase( LSS) gene on intestinal function in a mouse model of non-alcoholic fatty liver disease( NAFLD) induced by a high-fat diet． Methods: LSS gene heterozygous knockout C57 mice ( LSS + / －) were established using the CRISRP / Cas9 system．After being fed a high-fat diet with 60% fat content for 6 months，the fat deposition in liver tissues was detected by HE and Oil red O staining，the morphological changes of small intestine tissue were detected by HE staining．The changes in total cholesterol content in intestinal tissue were detected by kits．The gastrointestinal motility function of mice was detected by phenol red paste．The intestinal permeability was detected by Evans blue staining，and the expression of LSS，tight junction protein ( Claudin) -1，Claudin-5，cluster of differentiation 36 ( CD36) ，and Niemann-Pick type C1-like 1 protein ( NPC1L1) proteins in small intestinal tissues were detected by Western blot． Results : The results of HE and Oil red O staining of liver tissues showed that liver fat deposition in LSS gene heterozygous knockout mice was lower than that in wild-type mice in the high-fat diet group．The total cholesterol content in intestinal tis- sue of LSS gene heterozygous knockout mice decreased ( P ＜0. 01) ，but no morphological differences were ob- served between the two groups of mice by HE staining of intestinal tissues．The gastrointestinal motility function of LSS gene heterozygous knockout mice did not show significant changes．The intestinal permeability of LSS gene het- erozygous knockout mice in the high-fat diet group decreased as detected by Evans blue ( P＜0. 05) ．The expres- sion levels of Claudin-5 protein in the intestinal tissue of LSS gene heterozygous knockout mice in the high-fat diet group increased ( P ＜0. 05 ) ，while the expression of LSS protein in the intestinal tissues of LSS heterozygous knockout mice decreased ( P ＜0. 05) ． Conclusion In the NAFLD model induced by a high-fat diet，LSS gene heterozygous knockout reduces liver fat deposition induced by a high-fat diet and improves intestinal barrier function by regulating cholesterol metabolism in intestinal tissues and up-regulating the expression of Claudin-5．

OBJECTIVE: To explore the effects and mechanisms of the C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4) signaling axis on apoptosis and autophagy in SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. METHODS: SH-SY5Y cells were divided into the following groups: OGD/R group and non-OGD/R group, with the OGD/R group subjected to OGD/R modeling and the non-OGD/R group receiving no treatment. Cells were also divided into CXCL12⁺ and CXCL12^- groups; the CXCL12⁺ group received 0.1 mg/L exogenous recombinant CXCL12 (rhCXCL12) at reoxygenation, while the CXCL12^- group did not. Another set of cells was divided into CXCL12+AMD3100 and CXCL12 groups; the CXCL12+AMD3100 group was pretreated with 2.5 mg/L AMD3100, a CXCR4 inhibitor, for 2 hours before OGD/R and received both 2.5 mg/L AMD3100 and 0.1 mg/L rhCXCL12 at reoxygenation, whereas the CXCL12 group received rhCXCL12 only. Additionally, cells were divided into small interfering RNA CXCR4 (siCXCR4) and small interfering RNA negative control (siNC) groups; the siCXCR4 group underwent CXCR4 knockdown before OGD/R modeling and received 0.1 mg/L rhCXCL12 at reoxygenation, while the siNC group, transfected with a negative control, received the same treatment. Protein expression of autophagy-related 16 (ATG16), microtubule-associated protein 1 light chain 3 (LC3), aquaporin-3 (AQP3), and CXCR4 was detected by Western blotting. Apoptosis rate and CXCR4 expression were measured by flow cytometry. RESULTS: Compared with the non-OGD/R group, the OGD/R group showed a significantly increased apoptosis rate and markedly decreased protein expression levels of ATG16, LC3, AQP3, and CXCR4 (all P < 0.05). CXCR4 fluorescent expression was also significantly reduced, suggesting that OGD/R simultaneously affects neuronal apoptosis and autophagy while inhibiting CXCR4 and AQP3 expression in SH-SY5Y cells. Compared with the CXCL12^- group, the CXCL12⁺ group exhibited no significant change in apoptosis rate but demonstrated significantly increased protein expression of ATG16, LC3, and AQP3 (ATG16/GAPDH: 1.21±0.10 vs. 1.00±0.00; LC3/β-actin: 1.22±0.10 vs. 1.00±0.00; AQP3/β-actin: 1.26±0.04 vs. 1.00±0.00; all P < 0.05). CXCR4 expression was also significantly enhanced (fluorescence intensity: 1.19±0.05 vs. 1.00±0.00, P < 0.05), indicating that CXCL12 may promote autophagy in OGD/R-injured SH-SY5Y cells via the CXCR4/AQP3 pathway. Compared with the CXCL12 group, the CXCL12+AMD3100 group showed no significant difference in apoptosis rate but significantly lower protein levels of ATG16 and LC3 (ATG16/GAPDH: 0.75±0.08 vs. 1.00±0.00; LC3/GAPDH: 0.86±0.07 vs. 1.00±0.00; both P < 0.05), suggesting that CXCL12 induces autophagy in OGD/R SH-SY5Y cells through CXCR4. Compared with the siNC group, the siCXCR4 group showed no significant change in apoptosis rate but significantly reduced protein expression of ATG16, LC3, AQP3, and CXCR4 (ATG16/GAPDH: 0.76±0.06 vs. 1.00±0.00; LC3/GAPDH: 0.79±0.11 vs. 1.00±0.00; AQP3/GAPDH: 0.81±0.05 vs. 1.00±0.00; CXCR4/GAPDH: 0.86±0.04 vs. 1.00±0.00; all P < 0.05), indicating that CXCR4 knockdown suppresses OGD/R-induced autophagy in SH-SY5Y cells likely via AQP3. CONCLUSIONS The CXCL12/CXCR4 signaling axis can regulate OGD/R-induced autophagy in SH-SY5Y cells through AQP3 without affecting apoptosis, indicating a role for this pathway in neuronal autophagy during cerebral ischemia/reperfusion injury.
Humans ; Receptors, CXCR4/metabolism* ; Chemokine CXCL12/metabolism* ; Autophagy ; Glucose/metabolism* ; Apoptosis ; Neurons/cytology* ; Oxygen/metabolism* ; Signal Transduction ; Cell Line, Tumor ; Cell Hypoxia ; Benzylamines ; Cyclams

Objective : To investigate the effect of laminarin(LAM) on nonproliferative diabetes retinopathy by high throughput sequencing(RNA-seq). Methods : The diabetes model was established by intraperitoneal injection of streptozotocin(STZ), and the effect of LAM on diabetic mice was observed.C57BL/6 mice were randomly divided into three groups: Control group, Model group, and LAM group, with 8 mice in each group. After 8 weeks of modeling, the LAM group received a 4-week intraperitoneal injection of LAM treatment. Changes in blood glucose and body weight of the three groups of mice were recorded, HE staining was performed to examine retinal lesions, and RNA-seq was used to identify differentially expressed genes(DEGs) in diabetic retinopathy(DR) under the action of STZ and LAM. Results : STZ successfully established the model of DR, and LAM reduced the blood sugar in diabetic mice to a certain extent and improved the pathological morphology of retinal structural looseness in diabetic mice. After RNA-seq analysis of DEGs, it was found that there were a total of 214 DEGs in the retina of the Model group mice compared to the Control group. Enrichment analysis revealed that DR could exacerbate the lesions through the PI3K Akt signaling pathway. There were a total of 42 DEGs in the retina of the Model group and LAM group mice, and enrichment showed that LAM improved the lesions through the neutrophil extracellular trap pathway. Early growth response factor 1(Egr1), FBJ osteosarcoma oncogene(Fos), nuclear receptor subfamily 4A member 1(Nr4a1), and salt-induced kinase 1(Sik1) were regulated by STZ, and LAM significantly regulated their expression, which might be closely related to LAM′s treatment of diabetic retinopathy. Conclusion DEGs can exacerbate the severity of diabetic retinopathyviathe PI3K-Akt signaling pathway. LAM can mitigate diabetic retinopathyviathe neutrophil extracellular trap pathway. Egr1, Fos, Nr4a1, and Sik1 are key genes involved in LAM treatment of STZ-induced DR.

OBJECTIVE: To analyze the factors influencing the development of refeeding syndrome (RFS) in patients with sepsis and its impact on clinical prognosis. METHODS: A retrospective case-control study method was used to collect the clinical data of patients with sepsis admitted to the intensive care unit (ICU) of Qingdao Municipal Hospital from December 2018 to December 2023. The patients were divided into RFS and non-RFS groups according to whether RFS occurred, and the basic data, nutritional status and assessment scale, laboratory indicators, nutritional intake, medical history and prognosis were compared between the two groups. Binary multifactorial Logistic regression analysis was used to screen the influencing factors of the occurrence of RFS in patients with sepsis. RESULTS: A total of 544 patients with sepsis were finally enrolled, of whom 250 did not develop RFS and 294 developed RFS, with an incidence of 54.0%. Compared with the non-RFS group, the patients in the RFS group had lower body mass index (BMI), albumin, prealbumin, baseline electrolytes (serum phosphorus, serum potassium, and serum magnesium), creatinine-height index, and protein intake, and had higher nutritional risk screening 2002 (NRS2002) score, sequential organ failure assessment (SOFA) score, calorie intake, and the proportions of feedings during the 48 hours of ICU admission, history of diabetes and septic shock. Binary multifactorial Logistic regression analysis showed that BMI [odds ratio (OR) = 0.910, 95% confidence interval (95%CI) was 0.857-0.947, P < 0.001], SOFA score (OR = 1.166, 95%CI was 1.085-1.254, P < 0.001), albumin (OR = 0.946, 95%CI was 0.902-0.991, P = 0.019), baseline serum phosphorus (OR = 0.343, 95%CI was 0.171-0.689, P = 0.003), baseline serum potassium (OR = 0.531, 95%CI was 0.377-0.746, P < 0.001), creatinine-height index (OR = 0.891, 95%CI was 0.819-0.970, P = 0.008), caloric intake (OR = 1.108, 95%CI was 1.043-1.178, P = 0.001), protein intake (OR = 0.107, 95%CI was 0.044-0.260, P < 0.001), and feedings during the 48 hours of ICU admission (OR = 0.592, 95%CI was 0.359-0.977, P = 0.040) and septic shock (OR = 0.538, 95%CI was 0.300-0.963, P = 0.037) were independent influence factors on the occurrence of RFS in septic patients. Of the 544 patients, 267 died at 28 days, with a mortality of 49.1%. The 28-day mortality of patients in the RFS group was significantly higher than that in the non-RFS group [54.4% (160/294) vs. 42.8% (107/250); χ² = 7.302, P = 0.007]. 544 patients had a length of ICU stay of 20 (17, 24) days. The patients in the RFS group had a significantly longer length of ICU stay than that in the non-RFS group [days: 20 (17, 25) vs. 19 (17, 23); Z = -2.312, P = 0.021]. CONCLUSIONS The incidence of RFS in septic patients is high. Factors influencing the occurrence of RFS in septic patients include BMI, SOFA score, albumin, baseline serum phosphorus, baseline serum potassium, caloric intake, protein intake, feeding within 48 hours of ICU admission, and septic shock. RFS prolongs the length of ICU stay and increases the 28-day mortality in patients with sepsis.
Humans ; Retrospective Studies ; Sepsis/complications* ; Prognosis ; Refeeding Syndrome/etiology* ; Case-Control Studies ; Intensive Care Units ; Male ; Nutritional Status ; Female ; Risk Factors ; Middle Aged ; Logistic Models ; Body Mass Index ; Aged

Objective:To explore the psychological vulnerability characteristics of patients after percutaneous coronary intervention (PCI) based on symptom network analysis, and to provide evidence for maintining their psychological health.Methods:Using a cross-sectional survey method, from October 2023 to March 2024, a convenience sampling approach was employed to conduct a questionnaire survey among patients who underwent percutaneous coronary intervention (PCI) in the general ward of the Cardiology Department at Peking University Third Hospital. The survey involved a general information questionnaire and Mental Vulnerability Questionnaire. The R language was used to construct a symptom network to describe the relationship between each symptom of patients′psychological vulnerability, and its centrality index was calculated.Results:A total of 260 post-PCI patients were enrolled, including191 males and 69 females, with a mean age of (62.38 ± 12.91) years and a total psychological vulnerability score of (47.25 ± 13.18). Multiple linear regression analysis showed that the level of mental vulnerability was higher in patients with female gender ( β = 0.207, P = 0.001) and higher number of comorbidities/past history ( β = 0.126, P = 0.039). In the symptom network analysis, the symptoms with the highest node strength, tight centrality, and mediator centrality were "You often feeling unwell" ( rs = 1.25, rc = 0.003 45, rb = 2.61), "You always in a bad mood" ( rs = 1.15) and "You often have anxiety attacks" ( rs = 1.13) were second only to "You often feeling unwell" in the center of intensity. Conclusions:The core symptom of psychological vulnerability in post-PCI patients is "You often feeling unwell", and mental symptoms are in a more central position. Nursing staff should take mental symptoms as the target of intervention, and strengthen the holistic care for patients′physical-psychological-mental symptoms, so as to effectively reduce the level of psychological vulnerability of the patients, and to maintain their psychological health.