ObjectiveTo investigate the effects of Huangqi Jianzhongtang （HQJZ） on macrophage polarization and fat consumption in cancer cachexia （CC） mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to control the quality of HQJZ. （1） In vitro experiment： HQJZ-containing serum was prepared， and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages （RAW264.7） were cultured and randomly divided into six groups， including a blank group， a classically activated macrophages （M1） group， an alternatively activated macrophages （M2） group， a HQJZ + blank group， a HQJZ+M1 group， and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86， inducible nitric oxide synthase （iNOS）， CD206， and arginase-1 （Arg1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR ）. （2） In vivo experiment： Thirty-two BALB/c mice were randomly divided into a control group， a model group， a medroxyprogesterone acetate （MPA） group， and a HQJZ group. Except for the control group， the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA （0.13 g·kg^-1·d^-1） or HQJZ （13.13 g·kg^-1·d^-1） by gavage， respectively， while mice in the control and model groups were given an equal volume of saline by gavage， with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers （iNOS， Arg1， CD86， CD206） and fat browning-related genes uncoupling protein 1 （UCP1） and peroxisome proliferator-activated receptor γ （PPARγ） in epididymal adipose tissue. Western blot （WB） was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography （micro-CT） was used to measure residual fat volume， and hematoxylin-eosin （HE） staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro， the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that， compared with the blank group， Arg1 expression decreased in the HQJZ+blank group （P<0.05）， CD206 showed a downward trend without statistical significance， while iNOS and CD86 expression were significantly increased （P<0.05）. Compared with the M1 group， Arg1 and CD206 expression decreased in the HQJZ+M1 group （P<0.05）. Compared with the M2 group， CD206 expression decreased in the HQJZ+M2 group （P<0.05）， CD86 expression increased significantly （P<0.01）. In vivo， Real-time PCR results showed that， compared with the control group， CD86 and CD206 expression levels were significantly increased in the model group （P<0.01）. Compared with the model group， CD206 expression in the MPA group was significantly decreased （P<0.01）. In the HQJZ group， CD206 was significantly decreased （P<0.01）. WB results showed that， compared with the model group， protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group （P<0.05， P<0.01）. micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group （P<0.05）. HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group （P<0.05）. ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization， thereby delaying fat consumption in CC mice.

(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

Immune thrombocytopenia(ITP)is an autoimmune disease characterized primarily by bleeding and fatigue.ITP-related fatigue can substantially affect health-related quality of life and has been recognized as a treatment indication in the latest guidelines.However,its pathogenesis remains unclear,and targeted therapies are lacking.This paper explores the theoretical foundation of the"excessive fire consuming healthy qi"theory,linking two key conceptual pairs:"excessive fire"with inflammation and"healthy qi consumption"with mitochondrial dysfunction.Chronic inflammation leads to continuous"qi consumption"and damage to mitochondrial structure and function,ultimately resulting in symptoms of qi deficiency such as tiredness and fatigue.The imbalance between qi and fire,leading to imbalance of yin and yang,is the primary pathogenesis of ITP-related fatigue,with the disease mainly affecting the spleen.Considering the etiology and pathogenesis of ITP,and relative equilibrium of yin-yang,the therapeutic approach of invigorating spleen and benefiting qi to promote the production of blood serves as a core treatment strategy.Previous research has demonstrated the clinical efficacy of Jianpi Yiqi Shexue Formula,consisting of milkvetch root,tangshen,Indian bread,largehead atractylodes rhizome,India madder root,and ass hide glue in treating patients with ITP-related fatigue.Designed to invigorate the spleen and regulate qi and blood,this formula aligns with the pathogenesis of ITP-related fatigue characterized by deficiency of spleen qi and stomach qi.The formula also modulates the expression levels of key proteins and genes involved in mitochondrial energy metabolism and alleviates the immune dysfunction.These findings highlight the potential for further research into the mechanism of ITP-related fatigue,particularly by using inflammation-mediated mitochondrial energy metabolism as a promising entry point.

BACKGROUND:Aerobic exercise can suppress liver fibrosis in diabetic mice.However,the specific mechanism is yet to be elucidated.OBJECTIVE:To investigate the protective effect and mechanism of aerobic exercise on liver fibrosis in db/db mice via the transforming growth factor-β/Smad signaling pathway.METHODS:8-week-old male db/db mice and age-matched m/m mice were randomly divided into m/m control group,m/m+exercise group,db/db control group,and db/db+exercise group,with 10 mice in each group.Mice in the exercise group were subjected to a 12-week aerobic exercise.After the exercise,fasting blood glucose levels were measured in mice,and glucose tolerance and insulin tolerance tests were conducted.Mouse liver was extracted to calculate liver index and mouse eyeballs were taken to collect blood sample and detect biochemical indicators.Masson,oil red O and Hematoxylin-eosin staining were used to detect and analyze the pathological changes in mouse liver tissues.Immunohistochemistry was used to determine the protein expression levels of transforming growth factor-β1 and p-Smad3.Western blot analysis was applied to determine the protein expression levels of transforming growth factor-β1,Smad3,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen.RESULTS AND CONCLUSION:Compared with the m/m group and m/m+exercise group,body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels were significantly increased(P<0.01),but the high-density lipoprotein level significantly decreased(P<0.01)in the db/db group;the protein expressions of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen significantly increased(P<0.01)in the db/db group;the area under curve of glucose and insulin tolerance tests significantly increased(P<0.01)in the db/db group;and pathological staining of the liver in the db/db group showed extensive infiltration of inflammatory cells,increased lipid droplets,and significant fibrosis.In the db/db+exercise group,aerobic exercise could significantly reduce body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels(P<0.05 or P<0.01),and increase high-density lipoprotein level(P<0.05).Similarly,a marked decrease was observed in the protein expression levels of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen(P<0.05 or P<0.01)in the db/db+exercise group.In addition,the area under the curve of glucose tolerance and insulin tolerance tests significantly decreased(P<0.01,P<0.05),and pathological changes in liver tissues were significantly improved.In conclusion,aerobic exercise can attenuate liver fibrosis in diabetic mice,which may be related to the regulation of the transforming growth factor-β1/Smad signaling pathway.

Objective:To investigate the current status of fear of falling in postoperative cardiac surgery patients, and to analyze its influencing factors and interrelationships.Methods:A convenience sample of 246 postoperative cardiac surgery patients hospitalized in the Department of Cardiac Surgery, the First Affiliated Hospital of Xiamen University, from December 2023 to December 2024 was surveyed. The Body Image Scale, the Personal Mastery Scale, the Fear of Falling Questionnaire-Revised, and a self-designed demographic and clinical questionnaire were used for data collection. Pearson correlation analysis was conducted to examine the relationships among body image, personal mastery, and fear of falling. PROCESS Model 4 was applied to test the mediating role of personal mastery between body image and fear of falling, with bootstrapping for verification.Results:A total of 246 questionnaires were distributed, and 236 valid responses were obtained (valid response rate: 95.93%) . The body image score was (14.02±6.36) , personal mastery score was (20.44±4.16) , and fear of falling score was (38.28±10.83) . Body image was positively correlated with fear of falling ( r=0.324, P<0.01) , while personal mastery was negatively correlated with fear of falling ( r=-0.552, P<0.01) . After controlling for variables with statistically significant differences in univariate analysis (including sex, age, education level, body mass index, history of syncope, pain level, and self-rated preoperative exercise capacity) , PROCESS analysis showed that body image had a direct positive effect on fear of falling ( β=0.288, P<0.05) , and also indirectly affected fear of falling through personal mastery, with the indirect effect accounting for 49.5% of the total effect (0.237/0.525) . Conclusions:Postoperative cardiac surgery patients require improvement in body image, personal mastery, and fear of falling. Understanding how body image influences fear of falling through personal mastery not only enriches theoretical frameworks but also provides guidance for psychological interventions in clinical practice, thereby meeting patients' psychological support needs during rehabilitation.

Objective:To assess the effects of recognition function of four-lead electrocardiogram(ECG)synchronization technique and multi-parameter fusion technique in reducing the number of false alarms and improving the quality of alarms in intensive care units(ICU).Methods:Four-lead ECG synchronization technique and multi-parameter fusion technique were used to strengthen the monitoring and assessment for the alarm of clinical monitors,and reduce the false alarm rate of monitors.The clinical alarm data of bed units corresponding to 48 monitors in clinical use of ICU,cardiovascular intensive care unit(CCU)and neurosurgery intensive care unit(NICU)of Hainan General Hospital from October 14 to December 27,2024 were selected.According to the opening and close of the four-lead ECG synchronization and multi-parameter fusion technique algorithm of the monitors,they were divided into group A(opened four-lead ECG synchronization and multi-parameter fusion),group B(opened four-lead ECG synchronization,but closed multi-parameter fusion),group C(closed four-lead ECG synchronization,but opened multi-parameter fusion)and group D(closed four-lead ECG synchronization and multi-parameter fusion),with 12 units in each group.The numbers of total alarms and false alarms generated by monitor of each bed unit among different optimization strategies were compared.Results:The numbers of average daily alarm of the monitors in groups A,B and C were respectively(134.2±32.4)cases,(392.5±68.2)cases and(583.4±126.5)cases,which were lower than those in group D(1 073.2±168.6),with statistically significant differences(Z=3.45,2.94,2.52,P<0.05).The optimization rates of the alarm numbers in groups A,B and C were increased by 87.51%,63.47%and 45.67%,respectively.The rates of average false alarm of the monitors in groups A,B and C were respectively(1.04±0.15)%,(1.73±0.12)%and(2.07±0.08)%,which were lower than(3.76±0.2)%in group D,with statistically significant differences(Z=3.45,2.94,2.52,P<0.05).Conclusion:Four-lead ECG synchronization technique and multi-parameter fusion technique can effectively optimize the number of alarms in ICU,and reduce the proportion of false alarms of monitors in department,and decrease fatigue of medical staffs for alarm.

Background and Aims:Oncoplastic breast-conserving surgery(OBCS)integrates oncologic and plastic surgical techniques and includes two primary approaches:volume displacement and volume replacement.The pedicled lateral thoracic artery perforator(LTAP)flap is a commonly used technique for volume replacement.Although recent studies in China have confirmed its safety in OBCS,its patient-reported outcomes have not been systematically evaluated,and comparative data with volume displacement techniques remain lacking.Therefore,this study was performed to compare the clinical outcomes and patient satisfaction of LTAP flap versus mammoplasty(volume displacement)in OBCS,to inform surgical decision-making.Methods:A retrospective case-control study was conducted,including 106 patients with unilateral stage 0-Ⅲ breast cancer who underwent OBCS at the Affiliated Hospital of Southwest Medical University from January 2023 to June 2024.Patients were divided into the LTAP flap group(27 cases)and the mammoplasty group(79 cases)based on the surgical technique.Intraoperative variables,cosmetic outcomes,postoperative complications,and Breast-Q scores before and after surgery were compared between the two groups.Results:There were no significant differences between the two groups in clinicopathological characteristics or preoperative Breast-Q scores(all P>0.05).The LTAP group had longer operative times,larger excised tissue volumes,and greater postoperative drainage volumes(all P<0.001).Postoperative cosmetic outcomes were significantly better in the LTAP group,with a higher rate of excellent-to-good cosmetic results(88.9%vs.57.3%)and higher Breast-Q scores in breast satisfaction,psychosocial well-being,and physical well-being(all P<0.05).There were no significant differences in complication rates or local recurrence between the two groups(all P>0.05).Conclusion:In OBCS,the LTAP flap demonstrates comparable safety to mammoplasty while achieving superior cosmetic outcomes and patient satisfaction.It is particularly suitable for patients with small breast volumes requiring large tissue excision and holds promise for broader clinical application.

Objective To construct an acute cerebral infarction risk nomogram prediction model to evaluate the risk of symptomatic intracranial hemorrhage in patients after percutaneous intracranial artery thrombolysis.Methods A total of 272 patients with acute cere-bral infarction who underwent percutaneous intracranial artery thrombolysis in our hospital from January 2021 to February 2024 were selected as the study participants and divided into the training set(n=190)and validation set(n=82)at a ratio of 7∶3.The training set was divided into a bleeding group(n=61)and non-bleeding group(n=129)based on the presence or absence of symptomatic intracranial hemorrhage during the postoperative period,and the general data of the patients in the two groups were compared.Binary logistic regres-sion was used to analyze the factors influencing symptomatic intracranial hemorrhage.The R Language 4.3.3 toolkit was used to construct a predictive model for the risk of symptomatic intracranial hemorrhage.The predictive efficacy,calibration,and clinical applicability of the model were assessed using subject operating characteristic(ROC),calibration,and decision curves.Results Atrial fibrillation,fasting blood glucose level,and preoperative NIHSS scores were identified as factors influencing symptomatic intracranial hemorrhage after percutaneous intracranial artery thrombolysis in patients with acute cerebral infarction.The AUC of the training and validation sets for predicting symptomatic intracranial hemorrhage was 0.986(95％CI:0.974-0.999)and 0.986(95％CI:0.967-1.000),with a sensitivity of 95.08％and 99.98％,and a specificity of 95.35％and 92.98％.Conclusion The risk nomogram prediction model constructed in this study provides an effective tool of clinical value for assessing the risk of symptomatic intracranial hemorrhage after percutaneous intracra-nial artery thrombolysis in patients with acute cerebral infarction.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.