ObjectiveTo investigate whether esmolol could improve clinical outcome and tissue oxygen metabolism by controlling heart rate (HR) in patients with septic shock.Methods A single-center double-blinded randomized controlled trial was conducted. The patients suffering from septic shock received 6-hour early goal directed therapy (EGDT) with pulmonary artery wedge pressure≥ 12 mmHg (1 mmHg = 0.133 kPa) or central venous pressure (CVP)≥ 12 mmHg requiring norepinephrine to maintain mean arterial pressure (MAP)≥ 65 mmHg and HR≥95 bpm admitted to intensive care unit (ICU) of Guangdong General Hospital from September 2013 to September 2014 were enrolled. They were randomly divided into esmolol group and control group by computer-based random number generator. All patients received conventional basic treatment, while those in the esmolol group received in addition persistent esmolol infusion by micro pump with dosage of 0.05 mg·kg-1·min-1 with the dosage adjusted to maintain HR lower than 100 bpm within 24 hours. The patients in control group did not receive drug intervention for HR. The primary end-points consisted of length of stay in ICU and 28-day mortality. The secondary end-points included hemodynamic parameters [HR, MAP, CVP, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index (SVRI)] and tissue oxygen metabolism parameters [central venous oxygen saturation (ScvO2), lactate level (Lac)]before and 24, 48, 72 hours after the treatment.Results A total of 48 patients with septic shock were enrolled with 24 patients in esmolol group and 24 in control group.① The primary end-points: compared with control group, the length of stay in the ICU in the esmolol group was significantly shortened (days: 13.75±8.68 vs. 21.70±6.06,t = 3.680, P = 0.001), and 28-day mortality was significantly lowered [25.0% (6/24) vs. 62.5% (15/24),χ2 = 6.857,P = 0.009].② The secondary end-points: there were no significant difference in the hemodynamic and tissue metabolism parameters before treatment between two groups. No significant difference was found between before and after treatment of all above parameters in control group. HR and Lac in the esmolol group were obviously declined, SVI, SVRI, ScvO2 were gradually increased, but no significant difference in MAP, CVP, and CI was found. Compared with the control group, HR in the esomolol group was significantly lowered (bpm: 84.4±3.5 vs. 111.2±7.2,P< 0.01), SVRI and ScvO2 were significantly increased from 24 hours [SVRI (kPa·s·L-1·m-2): 137.9±1.6 vs. 126.9±1.3, ScvO2: 0.652±0.017 vs. 0.620±0.017, bothP< 0.01]; SVI was significantly increased (mL/m2: 39.9±2.2 vs. 36.8±1.7,P< 0.01) and Lac level significantly declined from 48 hours (mmol/L: 2.8±0.3 vs. 3.4±0.3,P< 0.01).Conclusion The results demonstrate that HR controlled by a titrated esmolol infusion given to septic shock patients was associated with an improvement in tissue metabolism, reduction in the length of ICU stay and lowering of 28-day mortality.

Objective To investigate the dosimetric performance of two algorithms for correcting the presence of tissue inhomogeneities,the finite site pencil beam (FSPB) and X-ray voxel Monte Carlo (XVMC) plans were implemented in the MONACO system,with the accuracy of application to clinic treatment of two algorithms were evaluated.Methods In a non-uniform artificial anthropomorphic phantom,regular open fields and intensity modulation radiated therapy (IMRT) plans of the MONACO were measured by using calibrated EBT2 films,and the dose accuracy of the two kinds of plans was analyzed by comparing the planned and measured plane dose.Results In an anthropomorphic phantom,the deviations between the calculated values by XVMC and the measured values by films were less than ± 2％.While the deviations of FSPB values between calculation and measurements was within ± 3％,except at the condition of 15 MV,10 cm ×2 cm field,the dose error in lung was up to 6.51％.The verification of individual IMRT beams based on films showed that the pass rates of calculation by XVMC and FSPB were larger than 90％ with γ criterion of 3％/3 mm and 4％/4 mm,respectively.At 3％/3 mm,the pass rates of FSPB were in the range of 80％-90％.At the same time,the pass rates of all individual fields were higher than 90％.Conclusions The accuracy of dose calculation of XVMC is better than that of FSPB when being in multi-segments and non-uniform media.The error of algorithm can be controlled within ±3％,for the calculation by XVMC.And the dose deficiency of PTV arising from algorithm can be avoided.

Objective To explore whether hypertonic saline would partake in regulating Notch signaling in microglia in experimentally induced cerebral ischemic rats.Methods Male SD rats were randomly divided into sham group, cerebral ischemia group, normal saline group ( NS group ) , 10%hypertonic saline group (10%HS group) , the model of cerebral ischemia were established in all rats except the sham group by using middle cerebral artery occlusion ( MCAO) .After 2 hours of MCAO, the rats were through reperfusion for 24 h.In addition, rats in the normal saline group and 10% HS group were respectively treated with a continuous intravenous injection of normal saline (0.3 mL/h) and 10%HS (0.3 mL/h) by tail vein for 24 h.Immunofluorescence methods, RT-PCR and Western blot were used to detect the expression of Notch1 and intracellular Notch receptor domain ( NICD) .All data was analyzed by one-way analysis of variance ( ANOVA) , The intergroup comparisons were analyzed by the least-significant-difference (LSD) tests.Differences were considered statistically significant if P<0.05.Results Immunofluorescence showed that the expression of Notch1 and NICD were significantly increased in the microglia around peri-ischemia area in cerebral ischemia group and normal saline group compared to sham group;the expression of Notch1 and NICD in the microglia around peri-ischemia area were significantly reduced in 10% HS group compared to ischemia group and NS group.RT-PCR showed that the mRNA expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 1.000 ± 0.076; ischemia group: 2.203 ±0.283; NS group: 1.616 ±0.185; P <0.01 ); however, it was significantly reduced in 10% HS group compared to ischemia group and NS group ( ischemia group:2.203 ±0.283; NS group: 1.616 ±0.185; 10%HS group: 1.202 ±0.177; P <0.05 ) .Western blot showed that the protein expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.290 ±0.079; ischemia group: 0.750 ±0.029; NS group:0.765 ±0.182;P<0.01);but was significantly reduced in 10%HS group compared to ischemia group and NS group ( ischemia group:0.750 ±0.029; NS group:0.765 ±0.182;10%HS group:0.390 ±0.195;P<0.05 ) .The protein expression of NICD was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.401 ±0.196; ischemia group: 0.906 ±0.359; NS group:0.847 ±0.153;P<0.01);but was significantly reduced in 10%HS group compared to ischemia group and NS group ( ischemia group:0.906 ±0.359; NS group:0.847 ±0.153;10%HS group:0.561 ±0.165;P<0.05 ) .Conclusion Our results suggest that HS markedly suppresses Notch signaling in microglia around the ischemia tissue area in experimental induced cerebral ischemic rats.

Objective:To investigate the effect of hypercapnia at admission on the clinical prognosis and the severity of infection in patients with severe community-acquired pneumonia (SCAP).Methods:The clinical data of 219 SCAP patients admitted to the department of emergency & critical care medicine of Guangdong Provincial People's Hospital from December 2017 to November 2019 were retrospectively analyzed. Based on the partial pressure of arterial carbon dioxide (PaCO 2) within 1 day after admission, the patients were divided into hypocapnia group [HO group, PaCO 2 < 35 mmHg (1 mmHg = 0.133 kPa)], normal carbonation group (NC group, PaCO 2 35-45 mmHg) and hypercapnia group (HC group, PaCO 2 > 45 mmHg). The clinical parameters of patients, such as gender, age, underlying diseases, white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), pH value and lactate (Lac) within 1 day after admission were reviewed. The oxygenation index (PaO 2/FiO 2), pneumonia severity index (PSI) score and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score were evaluated. The change tendencies of each index on day 1, day 3, and day 5 after admission were observed subsequently. Meanwhile, the rate of invasive mechanical ventilation (IMV), length of hospital stays and 28-day mortality among three groups were compared. Kaplan-Meier survival analysis was performed to assess the 28-day cumulative survival rate of patients with SCAP among three groups. Multivariate Logistic regression analysis was used to screen the risk factors of IMV and 28-day death in patients with SCAP. Results:Compared with the HO group ( n = 68) and NC group ( n = 72), the HC group ( n = 79) had higher proportion of preexisting comorbid chronic obstructive pulmonary disease (COPD) and PSI score, lower PCT, CRP, IL-6, and pH values. Compared with the HO group and NC group, there were smaller improvement trends on the levels of WBC, PCT, CRP, IL-6, PaO 2/FiO 2 and Lac at day 3 and day 5 as compared with day 1 in the HC group. On the 5th day after admission, the levels of WBC, PCT, CRP, IL-6, and Lac in the HC group were significantly higher than those in the HO group and NC group [WBC (×10 9/L): 18.33±1.44 vs. 10.89±2.37, 11.15±1.74; PCT (μg/L): 5.04±1.18 vs. 3.46±0.87, 3.58±0.83; CRP (mg/L): 78.43±7.17 vs. 54.24±4.97, 57.93±5.39; IL-6 (ng/L): 75.35±11.92 vs. 60.11±10.27, 57.88±12.34; Lac (mmol/L): 4.36±1.24 vs. 0.78±0.39, 0.86±0.64; all P < 0.01], and the lowest in PaO 2/FiO 2 was found in the HC group as compared with the HO and NC groups (mmHg: 171.31±6.73 vs. 226.68±7.36, 225.93±6.92, both P < 0.01). Compared with the HO group and NC group, the HC group had highest proportion of IMV (29.1% vs. 22.1%, 22.2%, both P < 0.01) and 28-day mortality (26.6% vs. 13.2%, 13.9%, both P < 0.01). Even when the patients with COPD were excluded from the analysis, the differences persisted among the groups. Kaplan-Meier survival analysis suggested that HC group had a higher 28-day cumulative survival rate as compared with the HO and NC groups (Log-Rank test: χ 12 = 4.976, P1 = 0.026; χ 22 = 4.629, P2 = 0.031). Multivariate Logistic regression analysis showed that IL-6, PSI score and hypercapnia within 1 day and PCT on the 5th day after admission were the independent risk factors of requiring IMV and 28-day death in patients with SCAP [odds ratio ( OR) were 0.325, 1.229, 1.396, 1.313, respectively, all P < 0.01]. Even when patients with COPD were excluded from the analysis, the above results had not been changed. Conclusion:Hypercapnia at admission was associated with higher proportion of IMV and 28-day mortality in patients with SCAP, which may be related to its early suppression of inflammation and then increment of infection.

Objective:This study aimed at reviewing surgical experiences and exploring risk factors for mortality and postoperative complications in patients with infracardiac total anomalous pulmonary venous connection (TAPVC).Methods:This retrospective study included 74 infants who underwent conventional repair (28 cases) and sutureless repair (46 cases) in one hospital from February 2009 to December 2022. Clinical data were reviewed to assess risk factors for mortality and postoperative pulmonary venous obstruction (PVO). Kaplan- Meier curves and cox regressions were applied to analyze the overall survival. Cumulative incidence curve and sub-distribution hazard models were used to evaluate postoperative PVO. Results:There were 4 early deaths and 3 late deaths, and the overall survival rate was 90.5%. A total of 12 patients complicated postoperative PVO. The median follow-up was 39.4 months ( IQR: 13.3 to 73.7 months). The overall survival rate was higher in the sutureless group than the conventional group ( P=0.003). The incidence rate of postoperative PVO in the conventional group was higher than that in the sutureless group ( P= 0.008). Risk factors for recurrent PVO included longer cardiopulmonary bypass time, the increase of direct bilirubin level and international normalized ratio level before surgical repair. Conclusion:Both sutureless and conventional repairs for patients with infracardiac TAPVC can achieve acceptable postoperative outcomes. Sutureless repair has a higher survival rate and a lower incidence of re-stenosis in pulmonary veins and anastomosis.

Objective To analyze the effect of the new conformal index(nCI)and the conventional conformal index(CI)on the treament planning quality of lung stereotopic radiotherapy(SBRT).Methods A total of 19 peripheral lung cancer patients,treated with SBRT in Fujian Medical University Union Hospital from 2014 to 2017,were analyzed retrospectively.Each patient was planned twice yielding identical CI and nCI.The prescription to 95％of planning target volume(PTV)was 48 Gy in four fractions,and renormalization was performed when needed for nineteen nCI plans.The Wilcoxon signed-rank test was used to examine the dosimetric index.Results The dose conformity plots indicate that nCI does not only reflect the dose to the organ at risk outside tumor,but also represents the dose distribution in the PTV.In addition,nCI was stricter with treatment planning qualities when the dose around PTV was closer to the prescribed dose.The value of target coverage(TC),the ratio of out-of-target volumes receiving 105％prescribed dose to the target volume(R105％),the ratio of volume covered by 50％isodose line to the target volume(R50％),and the ipsilateral lung V20were 98.70％,0.56,5.53,15.59％in the CI plans,vs.90％,0,4.99,14.42％in the corresponding nCI plans,respectively.All index were significantly lower in the nCI group(Z ＝-3.823,-3.180,-3.823,-3.783,respectively,P＜0.05).The ratio of the maximum dose to the 2 cm external margin from the PTV(D2 cm)to the maximum dose to the PTV were 63.70％and 64.07％respectively in the two groups,and the differences were not statistially significant(P＞0.05).The conformity values denoted a clinically favorable value as 1 between D95％and D99％of nCI plans,yet were not applicable to CI plans.Conclusions It is more clinically relavant to evaluate lung SBRT plans using nCI,TC and other indicators collectively than using CI alone.

Objective:To explore the mechanism of resveratrol on ameliorating the cognitive dysfunction induced by sepsis associated encephalopathy (SAE) in rats.Methods:The 12 weeks old male Sprague-dawley (SD) male rats were randomly divided into sham group, sepsis group and resveratrol group, with 30 rats in each group. The rat model of sepsis was made by injecting LPS (10 mg/kg) into tail vein. The rats in sham group was given the same amount of normal saline (NS). After LPS injection, resveratrol (8 mg·kg -1·d -1) was intraperitoneally injected once daily for 2 days in the resveratrol group; the same amount of NS was given to the sepsis group and sham group. At 24 hours after model establishment, the cognitive function of the experimental rats was assessed by the Morris water maze test. The blood-brain barrier (BBB) permeability was evaluated by the brain water content (BWC) and Evans blue (EB) test. The protein expressions of matrix metalloproteinase 9 (MMP-9), Occludin and Claudin-5 in cortical tissue were detected by Western Blot. Double immunofluorescence was used to verify the co-localization of MMP-9 protein and the marker protein of astrocyte GFAP in the cortical tissue of rats. Results:Compared with the sham group, the escape latency in the sepsis group was significantly longer [48-hour escape latency (s): 56.56±6.43 vs. 36.62±3.32, 72-hour escape latency (s): 57.72±7.23 vs. 26.46±4.24, both P < 0.01], the BWC and extravasation of EB were increased [BWC: (84.56±2.03)% vs. (76.82±2.22)%, EB (μg/g): 17.56±2.28 vs. 6.25±1.36, both P < 0.01], the expression of MMP-9 protein was increased (MMP-9/β-actin: 0.73±0.01 vs. 0.24±0.01, P < 0.01), the protein expressions of Occludin and Claudin-5 were decreased (Occludin/β-actin: 0.45±0.02 vs. 0.86±0.04, Claudin-5/β-actin: 0.62±0.03 vs. 0.96±0.05, both P < 0.01). At the same time, the co-localization expression of MMP-9 protein and the astrocytes of the cortical were increased [MMP-9 fluorescence intensity (AU): 38.66±4.26 vs. 17.23±3.04, MMP-9 positive cells: (26.92±1.77)% vs. (12.82±1.46)%, both P < 0.01]. Compared with the sepsis group, the escape latency in resveratrol group was significantly shorter [48-hour escape latency (s): 41.42±6.27 vs. 56.56±6.43, 72-hour escape latency (s): 33.46±7.17 vs. 57.72±7.23, both P < 0.01], the BWC and extravasation of EB were decreased [BWC: (77.15±2.27)% vs. (84.56±2.03)%, EB (μg/g): 7.74±1.88 vs. 17.56±2.28, both P < 0.01], the expression of MMP-9 protein was decreased (MMP-9/β-actin: 0.25±0.01 vs. 0.73±0.01, P < 0.01), the protein expressions of Occludin and Claudin-5 were increased (Occludin/β-actin: 0.82±0.03 vs. 0.45±0.02, Claudin-5/β-actin: 0.92±0.04 vs. 0.62±0.03, both P < 0.01). At the same time, the co-localization expression of MMP-9 protein and the astrocytes of the cortical were decreased [MMP-9 fluorescence intensity (AU): 19.44±4.37 vs. 38.66±4.26, MMP-9 positive cells: (13.11±1.29)% vs. (26.92±1.77)%, both P < 0.01]. Conclusion:Resveratrol can inhibit the expression of MMP-9 protein in the astrocytes of the cortical cortex of rats, and then reduce the degradation of tight junction proteins of Occludin and Claudin-5, thereby reducing BBB permeability and eventually ameliorate the cognitive dysfunction induced by SAE.

Objective:To develop a remote training system for CT simulation positioning of radiotherapy using virtual reality technology, and to explore a new method of medical training.Methods:The 3DMax and Maya were employed to establish the 3D model. The unity3D engine was adopted to develop 3D virtual operation and interaction system. Java spring MVC architecture was utilized as the system background service. MySQL was used as the background database system. The users were assigned into two roles: teacher and student, and the modes were divided into teaching and assessment modes.Results:The function of the system covered the whole process of CT simulation positioning, mainly including modules of patient information management, CT simulation positioning machine cognition, body position fixation technology, CT positioning scanning, and emergency handling, etc. Since it was put into use in 2018, the system has been running stably, with 14 920 pages views and an 86.66% pass rate. Compared with the traditional training, the training efficiency has been significantly improved and has received unanimous recognition.Conclusions:The remote training system can effectively improve the clinical practice ability and humanistic care ability of the trainees, which has good autonomy, sharing, and innovation. At present, the system has been put online and has strong popularization with prospects for broad application.

OBJECTIVE: To explore whether β1 receptor blocker could decrease the myocardial inflammation through the Toll-like receptor 4/nuclear factor-ΚB (TLR4/NF-ΚB) signaling pathway in the sepsis adult rats. METHODS: Sixty male Wistar rats (250-300 g) aged 3 months old were allocated to four groups by random number table (n = 15): sham operation group (S group), sepsis model group (CLP group), β1 receptor blocker esmolol intervention group (ES group), and inhibitor of the TLR4 E5564 intervention group (E5564 group). The rat sepsis model was established by cecal ligation and puncture (CLP); S group of rats underwent only an incision. Rats in S group, CLP group and E5564 group were subcutaneous injected with 0.9% sodium chloride (NaCl) 2.0 mL/kg. Besides, the rats in ES group were injected with esmolol (15 mg×kg^-1×h^-1) by micro pump through the caudal vein. The rats in E5564 group were injected with E5564 (0.3 mg×kg^-1×h^-1) by micro pump through the caudal vein 1 hour before the CLP surgery. Samples were collected 6 hours after the modelling in each group. The average arterial pressure (MAP) and cardiac output index (CI) were monitored by PU electrical conduction ECG monitor. The levels of serum cardiac troponin I (cTnI), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The expressions of TLR4, NF-ΚB p65, IL-1β, TNF-α in myocardial tissue was detected by Western Blot. RESULTS: There was no significant difference in MAP in each group. Compared with the S group, the CI in the CLP group was significantly decreased, the levels of serum cTnI, IL-1β, TNF-α were significantly increased, the protein expressions of myocardial tissue TLR4, NF-ΚB p65, IL-1β and TNF-α were significantly increased. Compared with the CLP group, the CI in the ES group and E5564 group were significantly increased (mL×s^-1×m^-2: 58.6±4.3, 58.9±4.4 vs. 41.2±3.9, both P < 0.01), the levels of serum cTnI, IL-1β and TNF-α were significantly decreased [cTnI (μg/L): 1 113.81±26.64, 1 115.74±25.90 vs. 1 975.96±42.74; IL-1β (ng/L): 39.6±4.3, 38.9±4.4 vs. 61.2±3.9; TNF-α (ng/L): 43.1±2.8, 48.7±2.6 vs. 81.3±4.4, all P < 0.01], the protein expressions of myocardial tissue NF-ΚB p65, IL-1β, TNF-α were significantly decreased (NF-ΚB p65/β-actin: 0.31±0.03, 0.43±0.04 vs. 0.85±0.08; IL-1β/β-actin: 0.28±0.05, 0.32±0.03 vs. 0.71±0.06; TNF-α/β-actin: 0.18±0.04, 0.28±0.03 vs. 0.78±0.07, all P < 0.01), but there was no significant difference in protein expression of TLR4 (TLR4/β-actin: 0.89±0.07, 0.87±0.09 vs. 0.95±0.09, both P > 0.05). There was no significant difference in CI, the levels of serum cTnI, IL-1β, TNF-α, and the protein expressions of myocardial tissue TLR4, NF-ΚB p65, IL-1β, TNF-α between ES group and E5564 group (all P > 0.05). CONCLUSIONS β1 receptor blocker esmolol may inhibit myocardial inflammatory response in sepsis adult rats through TLR4/NF-ΚB signaling pathway, thereby alleviating sepsis-induced myocardial injury.
Animals ; Inflammation/prevention & control* ; Interleukin-1beta ; Male ; Myocardium/pathology* ; NF-kappa B/metabolism* ; Propanolamines/pharmacology* ; Rats ; Rats, Wistar ; Sepsis/drug therapy* ; Signal Transduction/drug effects* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha

ObjectiveTo explore the protective effect of polysaccharide from Inonotus obliquus （IOP） on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice. MethodA total of 40 male C57BL/6 mice were randomly divided into normal group， model group， dexamethasone group， and high-dose and low-dose IOP groups， with eight mice in each group. The high-dose and low-dose IOP groups were administered intragastrically with IOP at 20 and 10 mg·kg^-1， respectively. The normal group and the model group were intragastrically administered with normal saline in equal volumes， and the dexamethasone group was intraperitoneally injected with dexamethasone phosphate injection of 30 mg·kg^-1 for 21 days. An ALI mouse model induced by LPS was constructed， and hematoxylin-eosin （HE） staining， immunofluorescence staining， and blood routine were used to detect pathological damage of lung tissue and blood cell content. Enzyme-linked immunosorbent assay （ELISA） and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression levels of various inflammatory factors. Changes in gut microbiota and plasma differential metabolites in mice were detected using 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）. ResultCompared with the model group， the lung tissue lesions of ALI mice were significantly improved after IOP administration， and the spleen and thymus index were dramatically increased （P<0.05， P<0.01）. The ratio of wet-to-dry weight of lung tissue was sensibly decreased （P<0.05， P<0.01）， and the number of lymphocytes was substantially increased （P<0.05， P<0.01）. The number of neutrophils was markedly decreased （P<0.01）. The expression level of interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-1β （IL-1β）， nuclear factor-κB（NF-κB）， and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） decreased prominently （P<0.05， P<0.01） and the expression level of interleukin-10 （IL-10） increased memorably （P<0.01）. The 16S rRNA sequencing results show that IOP can regulate and improve intestinal microbial disorders. The UPLC-Q-TOF-MS results indicate that the treatment of ALI mice with IOP may involve pathways related to mitochondrial， sugar， and amino acid metabolism， such as nucleotide sugar metabolism， histidine metabolism， ubiquinone， and other terpenoid compound-quinone biosynthesis， as well as starch and sucrose metabolism. ConclusionThe improvement of lung tissue lesions and inflammatory response by IOP in ALI mice may be related to maintaining intestinal microbiota balance， regulating mitochondrial electron oxidation respiratory chain， as well as sugar and amino acid metabolism pathways， and affecting the production of related microbial metabolites and tricarboxylic acid cycle metabolites.