ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

BackgroundThe mental health issues of medical staff have received increasing attention. Previous studies have mainly focused on the epidemiological characteristics and influencing factors， but there is a lack of sufficient understanding of the heterogeneity characteristics of the depression-anxiety symptoms network among medical staff. ObjectiveTo compare the differences in the depression-anxiety symptoms network between medical staff and community residents， so as to provide references for the promotion of the mental health of medical staff. MethodsFrom June 1， 2022 to December 31， 2024， a stratified random sampling method was used to recruit 1 959 medical staff from public hospitals and community health centers in 9 townships （industrial parks） of Dongguan City， Guangdong Province， as well as 2 412 community residents in this area， were selected as the research subjects. The general situation questionnaire， Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， and the Generalized Anxiety Disorder Scale-7 item （GAD-7） were used for investigation. The network visualization was conducted using the qgraph package of R 4.0.0. The centrality indicators of the network were calculated using the networktools package. The reliability of the network structure was evaluated using the bootnet package. The differences in the depression-anxiety symptoms network between medical staff and community residents were compared using the NetworkComparisionTest package. ResultsA total of 1 792 medical staff and 2 110 community residents completed the survey. The numbers of medical staff with mild， moderate and severe depressive symptoms were 381 （21.26%）， 217 （12.11%） and 169 （9.43%）， respectively， while the numbers of community residents were 322 （15.26%）， 98 （4.64%） and 66 （3.13%）， respectively. The numbers of medical staff with mild， moderate and severe anxiety symptoms were 411 （22.94%）， 126 （7.03%） and 93 （5.19%）， respectively， while the numbers of community residents were 320 （15.17%）， 73 （3.46%） and 18 （0.85%）， respectively. The comparison of the detection rates of depressive symptoms and anxiety symptoms between the two groups showed statistically significant differences （χ²=152.012， 205.953， P<0.01）. The network analysis results showed that the core symptom clusters of medical staff were "uncontrollable worry" "psychomotor retardation" "inability to relax"， and "depression"， while those of community residents were "uncontrollable worry" "inability to relax" "inferiority complex"， and "depression". There was a statistically significant difference in the network structure between the two groups （M=0.275， P<0.05）， and the overall connection strength of medical staff was lower than that of community residents （7.523 vs. 7.950， S=0.426， P<0.05）. ConclusionThe detection rates of depression and anxiety symptoms among medical staff were higher than those among community residents. The depression-anxiety symptoms network of medical staff was more concentrated， and the core symptoms were more prominent.［Funded by Social Development and Technology Project of Dongguan City （number， 20221800902552）］

BACKGROUND:Competitive athletes exercising in high-temperature,high-humidity,or low-oxygen environments experience intensified skeletal muscle deoxygenation and reduced fat oxidation,which can impair athletic performance.OBJECTIVE:To evaluate the impact of high-temperature,high-humidity,and low-oxygen environments on the fat oxidation rates of athletes during incremental load exercise,and to analyze the differences in deoxyhemoglobin kinetic parameters in skeletal muscle,thereby clarifying the relationship between fat oxidation capacity and skeletal muscle oxygenation under varying environmental conditions.METHODS:Twelve male modern pentathlon athletes were recruited for tests under three environmental conditions:normal(23 ℃,RH45％,FiO2=21.0％),high temperature and high humidity(35 ℃,RH70％,FiO2=21.0％),and low oxygen(23 ℃,RH45％,FiO2=15.6％).Resting metabolism and incremental load exercise were tested.Gas exchange data during and post-exercise were collected to calculate fat oxidation rate,carbohydrate oxidation rate,energy expenditure,and excess post-exercise oxygen consumption.Simultaneous measurements of SmO2 and total hemoglobin in the vastus lateralis muscle were used to calculate deoxyhemoglobin(HHb)levels.Deoxyhemoglobin change parameters-linear fittng slope(ΔEHHb),slope before the inflection point(ΔEHHB-1),and slope after the inflection point(ΔEHHB-2)-were determined using a bilinear function model.Fat oxidation curves were fitted using a SIN function model to identify the intensity(FATmax)that induced maximal fat oxidation(MFO),along with the curve's expansion,symmetry,and translation.RESULTS AND CONCLUSION:(1)Energy metabolism:No significant differences in maximal fat oxidation were observed across environments in each group(P>0.05).Compared with the normal environment group,both high temperature and high humidity group and low oxygen group showed significantly decreased time to maximal fat oxidation and FATmax(P<0.05).The percentage of maximal fat oxidation corresponding to peak oxygen uptake was lower in the low oxygen environment group(P<0.05).Fat oxidation was consistently low in the low oxygen environment group during exercise,while in the high temperature and high humidity environment group,it decreased only at higher exercise loads.Additionally,the expansion parameter was significantly reduced in both high temperature and high humidity and low oxygen environment groups(P<0.05).(2)Deoxyhemoglobin dynamics:The ΔEHHb was significantly higher in the high temperature and high humidity environment group,and ΔEHHB-1 was significantly increased in both high temperature and high humidity and low oxygen environment groups(P<0.05).(3)Correlation analysis:ΔEHHb was significantly negatively correlated with symmetry;ΔEHHB-1 was negatively correlated with FATmax and maximal fat oxidation;ΔEHHB-2 was positively correlated with maximal fat oxidation,and V?O2@BP was positively correlated with symmetry,expansion,and FATmax.(4)These findings indicate that incremental load exercise in high temperature,high humidity,and low oxygen environments accelerates skeletal muscle deoxygenation,thereby inhibiting fat oxidation capacity.Compared with high temperature and high humidity,low oxygen environments may more rapidly disrupt the balance between oxygen delivery and utilization in athletes'skeletal muscle,leading to a greater reliance on anaerobic glycolysis and a consequent reduction in fat oxidation capacity during exercise.

Objective:To observe the effect of ankle joint proprioception training on ankle joint proprioception, balance and gait in patients with thalamic infarction.Methods:Fifty-six patients with thalamic infarction were divided into a control group and a treatment group, each of 28, using a random number table. Both groups were given conventional lower limb rehabilitation training, but the treatment group was additionally provided with ankle joint proprioception training. Before and after 4 weeks of the treatment, the Tecnobody proprioception testing system was used to determine the average trajectory error rate (ATE) and the time taken in the test. The Berg Balance Scale (BBS) and a balance tester were used to assess balance. A gait analyzer was used to collect spatial-temporal measures of the patients′ walking, including the stride amplitude, stride rate, the proportion of the time spent in the swing phase, and foot dorsiflexion and plantarflexion angles.Results:After the treatment, the time used, ATE, ankle proprioception, BBS scores, static balance test scores, stability limits, stride length, stride rate, swing phase time percentage, and foot dorsiflexion and plantarflexion angles had improved in both groups compared with before the treatment ( P≤0.05). Compared with the control group, the treatment group had a smaller average ATE, spent less time on the ankle proprioception test, had higher BBS scores, had lower scores on the static balance test, had larger limits of stability, took longer strides at a faster rate, and spent a greater percentage of time in the swing phase. That group also showed greater ankle dorsiflexion and plantarflexion on average ( P≤0.05). ATE difference of the affected lower limb and the time to complete the ankle proprioception test were positively correlated with the gap in the static balance ability test, and negatively correlated with the gaps in the BBS score, the limits of stability, stride length, stride rate, and the time share of the swing phase, as well as the dorsiflexion and plantarflexion angles of the foot. Conclusions:Ankle proprioception training, in addition to effectively improving ankle proprioception, can improve the balance and gait of persons with thalamic infarction. It is worthy of clinical application and promotion.

Objective:To investigate the expression of SLIT2/ROBO1 in prostate cancer and its clinical significance.Methods:A total of 100 cases of radical prostatectomy paraffin specimens at Department of Clinical Pathology, the average age of the patients was (71.8±7.8) years, the People?s Hospital of Baoan Shenzhen from January 2015 to December 2019 were collected and immunohistochemical staining was used to analyze the correlation between SLIT2/ROBO1 expression and clinicopathological features in prostate cancer.COX regression was used to analyze the influencing factors of biochemical recurrence in patients with prostate cancer after radical treatment.Prostate cancer cells PC3 and LNCaP were used as research objects, ROBO1 was silenced by small interfering RNA specific to human ROBO1, and its effect on the growth rate of prostate cancer was observed by CCK8 assay.Transwell cell migration and invasion assay was used to detect the effect of ROBO1 knock-down on the migration and invasion ability of prostate cancer cells.Protein immunoimprinting assay was used to detect the expression of TGF-β/SMAD pathway-related proteins after ROBO1 knockdown.Results:The expressions of SLIT2 and ROBO1 in prostate cancer were increased with the increase of prostate cancer Gleason score system (Gleason score) and International Society of Urology Pathology score (ISUP)( P<0.05). The expression was significantly up-regulated in prostate cancer tissues with lymph node metastasis ( P<0.01) and T3 stage.In addition, COX regression univariate analysis showed that age, preoperative PSA level, Gleason and ISUP scores, T stage, lymph node metastasis and ROBO1 protein expression status were correlated with postoperative biochemical recurrence.COX regression multivariate analysis showed that ROBO1 high expression, age, preoperative PSA value and T stagewere risk factors for the prognosis of prostate cancer ( P<0.05).The results of cell experiments showed that ROBO1 promoted the proliferation, migration and invasion of prostate cancer cells.The expression of TGF-β/SMAD was decreased after ROBO1 knockdown and SLIT2/ROBO1 inhibitor (P144)treatment, respectively. Conclusions:The high expression of SLIT2 and ROBO1 is associated with the progression and differentiation of prostate cancer.The high expression of ROBO1 is a risk factor for biochemical recurrence of prostate cancer.At the same time, ROBO1 can inhibit the migration and invasion of prostate cancer cells by regulating the TGF-β/SMAD signaling pathway.

Objective:To investigate the effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Objective:To investigate the effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.