Objective To explore the efficacy of a compound nutrition preparation on wound healing after acute trauma and investigate the underlying mechanism primarily.Methods After skin wound model was successfully constructed on totally 60 male SD rats surgically,they were randomly divided into control group(CON group),whey protein group(WP group)and low-and high-dose nutritional formula groups(LDF and HDF groups),with 15 animals in per group.From the next day after surgery,the rats in each group were given corresponding nutritional interventions for 2 weeks.During the intervention,the wound conditions were observed and recorded,and the wound area was measured.The samples were collected on the 3rd,7th and 14th days after surgery,respectively.Serum albumin(ALB),prealbumin(PA),total protein(TP),inflammatory factors(TNF-α,IL-1β,IL-6 and IL-10),immunoglobulins(IgA,IgG and IgM)and hydroxyproline(Hyp)were detected by the corresponding reagent kits.The histopathologic changes of wound were observed with HE staining.Masson staining was used to observe the collagen fiber deposition in wound tissue.The angiogenesis of wound tissue was evaluated by immunohistochemical staining.Results Compared with the CON group,the wound healing speed,collagen synthesis and angiogenesis speed were significantly accelerated in the WP group,LDF group and HDF group(P＜0.05),and the effects were the most obvious in the HDF group.On the 3rd day after surgery,in the WP,LDF and HDF groups,the serum ALB,PA and TP levels were significantly increased(P＜0.05),serum TNF-α and IL-1β levels were obviously decreased(P＜0.05),and serum IL-10 level was notably increased(except WP group)when compared with the CON group.The serum IgG and IgM levels were significantly increased in the LDF group and HDF group(P＜0.05)and significant increment of IgA was only observed in the HDF group(P＜0.05).On the 7th day after modeling,the levels of ALB,PA and TP were significantly increased(P＜0.05),the levels of TNF-α,IL-1β and IL-6 were obviously decreased(P＜0.05),and the levels of IL-10 were remarkably increased(P＜0.05)in the HDF group than the CON group;The LDF group and HDF group had significantly elevated serum IgG and IgM levels(P＜0.05),but only the former group had statistically increased serum IgA level(P＜0.05).On the 14th day after modeling,the HDF group had significantly increased levels of ALB and TP(P＜0.05),decreased levels of IL-1β(P＜0.05),and raised levels of IgG and IgM when compared with the CON group(P＜0.05).Conclusion Our compound nutrition preparation promotes wound healing in rat model of acute trauma,which might be related to its improving the nutritional status,promoting collagen synthesis,and thus alleviating inflammatory response and enhancing immune function.

With the development of population aging, the incidence of lower limb artery ischemic diseases is gradually increasing. Although various treatments such as medication and endovascular surgery are currently available, patients with compromised microcirculation in the distal limbs and poor outflow pathways often do not achieve satisfactory results. Additionally, these treatments can be costly, and long-term patency rates are not ideal. The amendment in situ autologous great saphenous vein arterialization surgery utilizes the patient′s great saphenous vein to provide arterial blood in a retrograde manner and re-establishes blood supply to the tissues through the venous microcirculation system in the distal foot. This approach can achieve good limb salvage results and long-term patency. Therefore, this article aims to elaborate on the methods and value of amendment in situ autologous great saphenous vein arterialization surgery.

Objective:To evaluate the Efficacy of bicarbonate Ringer′s solution (BRS) for early fluid resuscitation in patients with septic shock.Methods:In this prospective cohort study, 80 patients of either sex with septic shock, aged 18-80 yr, with a body mass index of 18-30 kg/m 2, who required early fluid resuscitation at the Anesthesiology and Intensive Care Unit of the Second Hospital of Hebei Medical University from April 2021 to April 2023, were included and divided into lactated Ringer′s solution group (LR group, n=40) and bicarbonate Ringer′s solution group (BR group, n=40). After the corresponding crystalloid solution 30 ml/kg was intravenously infused over 3-6 h for resuscitation, vasopressor drugs were used to achieve the goal of resuscitation: central venous pressure 8-12 mmHg, mean arterial pressure≥65 mmHg, urine volume> 0.5 ml·kg -1·h -1, the superior vena cava oxygen saturation≥0.7. Arterial blood gas analysis was performed immediately after the diagnosis of septic shock (before resuscitation), immediately after the end of fluid resuscitation and at 6 h after the diagnosis. The vasoactive-inotropic score was calculated. The plasma syndecan-1 concentration and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine (Cr) concentrations were measured by enzyme-linked immunosorbent assay before resuscitation and at 24 h after resuscitation. The 28-day all-cause mortality was recorded. Results:The pH value and HCO 3- concentration were significantly increased immediately after the end of resuscitation in BR group compared with the baseline before resuscitation ( P<0.05). Compared with LR group, the HCO 3- concentration, normal rate of lactic acid and improvement rate of AST were significantly increased immediately after the end of resuscitation ( P<0.05), and no significant change was found in the other parameters of blood gas analysis, vasoactive-inotropic score, plasma syndecan-1 concentrations, concentrations of ALT, AST and Cr in serum, improvement rate of ALT, improvement rate of Cr, and 28-day all-cause mortality in BR group ( P>0.05). Conclusions:Bicarbonate Ringer′s solution is superior to lactated Ringer′s solution for early fluid resuscitation in the patients with septic shock.

Objective To explore the relationship between postoperative restenosis and vascular endothelial function in patients with lower extremity arterial disease(LEAD).Methods A retrospective analysis was performed on 133 patients with diabetic lower extremity arteriopathy who had successfully undergone interventional therapy in our hospital,and the patients were followed up for one year,and the patients were grouped according to whether restenosis occurred,with 25 cases in the restenosis group and 108 cases in the non-stenosis group.The patient's vascular endothelial function index,inflammatory factor level,blood lipid four items and hemoglobin A1c(HbAlc)were detected,and peripheral blood cells of patients in the stenosis group and non-stenosis group were isolated for transcriptome sequencing.Multivariate unconditional logistic regression analysis was used to screen for independent risk factors for vascular endothelial function in postoperative restenosis.Results Serum endothelin-1(ET-1),von Willebrand factor(vWF),thromboxane B2(TXB2),vascular cell adhesion protein 1(VCAM-1),and nitric oxide(NO)were significantly higher in the stenosis group than in the non-stenosis group,while endothelial nitric oxide synthase(eNOS)and vascular endothelial growth factor(VEGF)were significantly lower than those in the non-stenosis group(P<0.01).There was no significant difference in blood lipids between the two groups(P>0.05).The HbAlc of the stenosis group was significantly higher than that of the non-stenosis group(P<0.01).The inflammatory factors in the stenosis group were significantly higher than those in the non-stenosis group(P<0.05).Transcriptome sequencing analysis results are consistent with test results.Multivariate Logistic regression analysis showed that TNF-α,IL-6,ET-1,and vWF were independent risk factors for LEAD vascular restenosis(P<0.05).Conclusion Vascular endothelial function indexes(ET-1,vWF)and inflammatory factors(TNF-α,IL-6)are independent risk factors for restenosis after interventional surgery.

Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess anti-insomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmaco-metabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine N-methyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.

Objective:To evaluate the Efficacy of bicarbonate Ringer′s solution (BRS) for early fluid resuscitation in patients with septic shock.Methods:In this prospective cohort study, 80 patients of either sex with septic shock, aged 18-80 yr, with a body mass index of 18-30 kg/m 2, who required early fluid resuscitation at the Anesthesiology and Intensive Care Unit of the Second Hospital of Hebei Medical University from April 2021 to April 2023, were included and divided into lactated Ringer′s solution group (LR group, n=40) and bicarbonate Ringer′s solution group (BR group, n=40). After the corresponding crystalloid solution 30 ml/kg was intravenously infused over 3-6 h for resuscitation, vasopressor drugs were used to achieve the goal of resuscitation: central venous pressure 8-12 mmHg, mean arterial pressure≥65 mmHg, urine volume> 0.5 ml·kg -1·h -1, the superior vena cava oxygen saturation≥0.7. Arterial blood gas analysis was performed immediately after the diagnosis of septic shock (before resuscitation), immediately after the end of fluid resuscitation and at 6 h after the diagnosis. The vasoactive-inotropic score was calculated. The plasma syndecan-1 concentration and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine (Cr) concentrations were measured by enzyme-linked immunosorbent assay before resuscitation and at 24 h after resuscitation. The 28-day all-cause mortality was recorded. Results:The pH value and HCO 3- concentration were significantly increased immediately after the end of resuscitation in BR group compared with the baseline before resuscitation ( P<0.05). Compared with LR group, the HCO 3- concentration, normal rate of lactic acid and improvement rate of AST were significantly increased immediately after the end of resuscitation ( P<0.05), and no significant change was found in the other parameters of blood gas analysis, vasoactive-inotropic score, plasma syndecan-1 concentrations, concentrations of ALT, AST and Cr in serum, improvement rate of ALT, improvement rate of Cr, and 28-day all-cause mortality in BR group ( P>0.05). Conclusions:Bicarbonate Ringer′s solution is superior to lactated Ringer′s solution for early fluid resuscitation in the patients with septic shock.

Objective:To propose recommendations for noise protection and control measures in high-performance fighter cockpits by investigating the noise exposure of pilots in cockpits.Methods:In the ground test for 3 types of high-performance fighters (J-A, J-B and J-C), the total sound pressure level (SPL), A sound level, as well as the linear SPL at 31.5, 63, 125, 250, 500, 1 000, 2 000, 4 000, 8 000 Hz were respectively measured by the sound level meter installed at ear position of a dummy pilot in cockpit and at 2.5 m away along the line started at right tail nozzle and 60° off the aircraft longitudinal axis when the engine accelerated to its maximum speed for 5-180 s. Ten young male volunteers with normal hearing were selected to use 125, 250, 500, 1 000, 2 000, 4 000, 8 000 Hz octave center frequency narrowband signals, respectively, to test their hearing thresholds with and without 3 types of flight helmet (imported, in-service, and newly developed) under active and passive noise reduction conditions. The sound attenuation values of the helmets (difference between the bare-ear threshold and the threshold with the helmet) were calculated.Results:The total SPL at the ear position of the dummy pilot in the cockpits of J-A, J-B, and J-C during ground test at maximum engine operation was 102.2, 100.4, 111.2 dB, respectively; the total SPL at the tail nozzle of J-B and J-C was 134.4, 148.0 dB, respectively. The cockpit noise of J-C exceeded the limit standard of GJB 565A—2009. Except for the measure at 4 000 Hz, the sound attenuation values of different helmets at other frequencies were significantly different ( H=35.49, 38.93, 32.37, 33.50, 23.96, 27.81, all P<0.001). By attenuating under active state of Type B helmet, the total noise exposure SPL in the cockpits of J-A, J-B, and J-C was 87.3, 84.1, 89.3 dB, respectively. Conclusions:The noise in high performance aircraft cockpit still exposes pilot in relatively high SPL. It still poses the potential threat to pilot′s hearing health and performance. Helmet noise attenuation needs further development. The active attenuation of helmet, as well as the reduction of the source noise level is still the main goal of noise protection.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective:To propose recommendations for noise protection and control measures in high-performance fighter cockpits by investigating the noise exposure of pilots in cockpits.Methods:In the ground test for 3 types of high-performance fighters (J-A, J-B and J-C), the total sound pressure level (SPL), A sound level, as well as the linear SPL at 31.5, 63, 125, 250, 500, 1 000, 2 000, 4 000, 8 000 Hz were respectively measured by the sound level meter installed at ear position of a dummy pilot in cockpit and at 2.5 m away along the line started at right tail nozzle and 60° off the aircraft longitudinal axis when the engine accelerated to its maximum speed for 5-180 s. Ten young male volunteers with normal hearing were selected to use 125, 250, 500, 1 000, 2 000, 4 000, 8 000 Hz octave center frequency narrowband signals, respectively, to test their hearing thresholds with and without 3 types of flight helmet (imported, in-service, and newly developed) under active and passive noise reduction conditions. The sound attenuation values of the helmets (difference between the bare-ear threshold and the threshold with the helmet) were calculated.Results:The total SPL at the ear position of the dummy pilot in the cockpits of J-A, J-B, and J-C during ground test at maximum engine operation was 102.2, 100.4, 111.2 dB, respectively; the total SPL at the tail nozzle of J-B and J-C was 134.4, 148.0 dB, respectively. The cockpit noise of J-C exceeded the limit standard of GJB 565A—2009. Except for the measure at 4 000 Hz, the sound attenuation values of different helmets at other frequencies were significantly different ( H=35.49, 38.93, 32.37, 33.50, 23.96, 27.81, all P<0.001). By attenuating under active state of Type B helmet, the total noise exposure SPL in the cockpits of J-A, J-B, and J-C was 87.3, 84.1, 89.3 dB, respectively. Conclusions:The noise in high performance aircraft cockpit still exposes pilot in relatively high SPL. It still poses the potential threat to pilot′s hearing health and performance. Helmet noise attenuation needs further development. The active attenuation of helmet, as well as the reduction of the source noise level is still the main goal of noise protection.