Comparison of the efficacy and safety of sodium valproate versus levetiracetam in the treatment of severe traumatic brain injury.

OBJECTIVE: To observe the efficacy and safety of sodium valproate (VPA) compared to levetiracetam (LEV) in the treatment of severe traumatic brain injury (sTBI). METHODS: In this blind, prospective study, eighty-four sTBI patients who had craniotomy from August 2021 to August 2023 were randomly split into two groups through random number table method: LEV and VPA, each with 42 patients. Both received comprehensive treatment post-craniotomy. LEV group: LEV injection on surgery day, transitioning to LEV tablets from day two. VPA group: VPA injection on surgery day, switching to VPA extended-release tablets from day two. The study compared hospital stay, neurological function, clinical outcomes, seizures, and drug reactions between groups. RESULTS: The length of hospital stay showed no significant difference between the LEV and VPA groups. Both groups demonstrated improved neurological function post-treatment (NIHSS and BI scores), with no significant between-group differences. Clinical outcomes at 3 months post-treatment were similar in both groups. Seizure occurrence within 3 months after treatment showed no significant difference between the LEV (19.05%) and VPA (23.81%) groups. However, the VPA group experienced a significantly higher rate of drug-related adverse reactions (40.48%) compared to the LEV group (21.43%). CONCLUSION: Both VPA and LEV are effective in treating sTBI, showing no significant difference in improving neurological function, daily life abilities, treatment outcomes, and seizure occurrence. However, VPA treatment exhibited a significantly higher incidence of drug-related adverse reactions compared to LEV, indicating that LEV might be a safer option for sTBI treatment.

Prognostic stratification of sepsis through DNA damage response based RiskScore system: insights from single-cell RNA-sequencing and transcriptomic profiling.

Background: A novel risk scoring system, predicated on DNA damage response (DDR), was developed to enhance prognostic predictions and potentially inform the creation of more effective therapeutic protocols for sepsis. Methods: To thoroughly delineate the expression profiles of DDR markers within the context of sepsis, an analytical approach utilizing single-cell RNA-sequencing (scRNA-seq) was implemented. Our study utilized single-cell analysis techniques alongside weighted gene co-expression network analysis (WGCNA) to pinpoint the genes that exhibit the most substantial associations with DNA damage response (DDR). Through Cox proportional hazards LASSO regression, we distinguished DDR-associated genes and established a risk model, enabling the stratification of patients into high- and low-risk groups. Subsequently, we carried out an analysis to determine our model's predictive accuracy regarding patient survival. Moreover, we examined the distinct biological characteristics, various signal transduction routes, and immune system responses in sepsis patients, considering different risk categories and outcomes related to survival. Lastly, we conducted experimental validation of the identified genes through in vivo and in vitro assays, employing RT-PCR, ELISA, and flow cytometry. Results: Both single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic analyses have demonstrated a strong correlation between DNA damage response (DDR) levels and sepsis prognosis. Specific cell subtypes, including monocytes, megakaryocytes, CD4+ T cells, and neutrophils, have shown elevated DDR activity. Cells with increased DDR scores exhibited more robust and numerous interactions with other cell populations. The weighted gene co-expression network analysis (WGCNA) and single-cell analyses revealed 71 DDR-associated genes. We developed a four-gene risk scoring system using ARL4C, CD247, RPL7, and RPL31, identified through univariate COX, LASSO COX regression, and log-rank (Mantel-Cox) tests. Nomograms, calibration plots, and decision curve analyses (DCA) regarding these specific genes have provided significant clinical benefits for individuals diagnosed with sepsis. The study suggested that individuals categorized as lower-risk demonstrated enhanced infiltration of immune cells, upregulated expression of immune regulators, and a more prolific presence of immune-associated functionalities and pathways. RT-qPCR analyses on a sepsis rat model revealed differential gene expression predominantly in the four targeted genes. Furthermore, ARL4C knockdown in sepsis model in vivo and vitro caused increased inflammatory response and a worse prognosis. Conclusion: The delineated DDR expression landscape offers insights into sepsis pathogenesis, whilst our riskScore model, based on a robust four-gene signature, could underpin personalized sepsis treatment strategies.

Exosomes derived from BMSCs ameliorate cyclophosphamide-induced testosterone deficiency by enhancing the autophagy of Leydig cells via the AMPK-mTOR signaling pathway.

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders. Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here, we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting the expression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentration in serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos could be absorbed by LCs through the blood-testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serum testosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promote autophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor, 3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exos promote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novel evidence for the clinical improvement of CPTD using BMSCs-exos.

The effect of preoperative application of butorphanol tartrate on the quality of recovery in patients undergoing thoracoscopic lobectomy / 中国医师杂志

Objective:To observe the effect of preoperative application of butorphanol tartrate on postoperative recovery quality in patients undergoing thoracoscopic lobectomy.Methods:A prospective selection was conducted on 96 lung cancer patients who underwent thoracoscopic lobectomy and were admitted to Linyi People′s Hospital from May 2021 to September 2021. They were randomly divided into observation group and control group using a random table number method, with 48 patients in each group. The observation group received intravenous injection of 0.02 mg/kg butorphanol tartrate 15 minutes before anesthesia induction; The control group was given an equal volume of physiological saline. The operation site, operation time, remifentanil dosage during operation, heart rate (HR) and mean arterial pressure (MAP) at each time point of admission (T 0), intubation (T 1), 5 min after intubation (T 2), extubation (T 3), 5 min after extubation (T 4), and 15 min into post-anaesthesia care unit (PACU) (T 5) were recorded; The awakening Restlessness score (RS), Ramsay score, Visual Analogue Scale (VAS) score at T 4 and T 5, the time required from completion to extubation, and postoperative anesthesia related adverse reactions were evaluated. Results:There was no significant difference in the operation site, operation time and remifentanil dosage between the two groups (all P>0.05). Compared with T 0, the HR at T 2, T 3 and T 4, MAP at T 1, T 2, T 3 and T 4 in the two groups decreased significantly (all P<0.05). The HR of the observation group at T 1 and T 3 was significantly lower than that of the control group, and the difference was statistically significant (all P<0.05). The VAS scores of T 4 and T 5 in the observation group were lower than those in the control group after surgery, while the Ramsay score were higher than those in the control group (all P<0.001). The incidence of postoperative restlessness, nausea and vomiting in the observation group was lower than that in the control group ( P<0.05). Conclusions:Administering 0.02 mg/kg butorphanol tartrate 15 minutes before anesthesia induction can improve the quality of recovery in patients undergoing thoracoscopic lobectomy, reduce restlessness and related adverse reactions during recovery.

Stability and taste evaluation of two kinds of oral solvent after extemporaneous compounding / 药学学报

A flavoring agent and a suspension agent were prepared for extemporaneous compounding. The stability of the two agents before and after drug loading was investigated, and the taste of the suspension after extemporaneous compounding was evaluated by electronic tongue technology. The two agents remained stable under the conditions of influence factor test, accelerated test and long-term test. The appearance properties of the two agents did not change. The relative density of the flavoring agent was maintained at 1.053-1.075, and the pH was stable at 4.2-4.5. The relative density of the suspension agent was maintained at 0.999-1.022, and the pH was stable at 4.0-4.5. Seven kinds of drugs, including warfarin sodium tablets and spironolactone tablets, were mixed with these two oral solvents, and the content uniformity and stability were detected respectively. The results showed that the preparations could be evenly dispersed and the physical and chemical properties were stable. The results of taste evaluation showed that in captopril group and chloral hydrate group, the flavoring agent had the best effect on taste correction. In warfarin sodium group, rifampicin group, spironolactone group, vitamin B1 group and vitamin B2 group, the blending agents had the best effect on taste correction.

Triamcinolone Acetonide combined with Aflibercept in the treatment of wet age-related macular degeneration with poor response to Ranibizumab / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficacy and safety of intravitreal injection of aflibercept combined with posterior sub-fascial injection of triamcinolone acetonide in the treatment of wet age-related macular degeneration(ARMD)with poor response to anti-vascular endothelial growth factor drugs.METHODS: Retrospective cohort study. From June 2018 to May 2020, a total of 60 patients(60 eyes)with refractory ARMD who had poor response to the treatment of anti VEGF drug ranibizumab were randomly divided into the control group of aflibercept and the observation group of triamcinolone acetonide combined with aflibercept, with 30 patients(30 eyes)in each group. Once a month, the patients in the two groups received intravitreal injection of aflibercept alone or intravitreal injection of aflibercept combined with posterior sub-fascial injection of triamcinolone acetonide for three consecutive times. The changes of best corrected visual acuity(BCVA), central macular thickness(CMT)and intraocular pressure were reviewed before injection and 1, 3 and 6mo after the third injection.RESULTS: The BCVA and CMT of the two groups were significantly improved 1, 3 and 6mo after the injection of the drug(P&#x003C;0.05). The mean intraocular pressure in the combined group was higher at 1mo after treatment than before, but it still within the normal range. There was a significant difference in intraocular pressure between the two groups(17.50±4.60 vs. 18.30±3.73mmHg, P&#x003C;0.05).CONCLUSION: Triamcinolone acetonide injection under the posterior fascia of the eyeball combined with intravitreal injection of aflibercept in the treatment of wet ARMD can effectively reduce macular edema and improve vision, which is more safe and reliable.

Correlation between body mass index and elbow vein grading in patients with metabolic syndrome based on superficial vein evaluation / 中国实用护理杂志

Objective:To analyze the correlation between body mass index (BMI) and the graded expression, subcutaneous depth, and diameter of elbow veins (cephalic vein, median vein, basilic vein) in patients with metabolic syndrome, to provide a method and theoretical basis for precise puncture of peripheral veins in obese patients.Methods:From January to October 2021, a total of 767 patients with metabolic syndrome with gastric volume reduction were selected as the study subjects by retrospective cohort study from the first Affiliated Hospital of Nanjing Medical University. According to the quartile Q1, M and Q3 of BMI level, they were divided into four groups: group A, group B, group C and group D. The subcutaneous depth and diameter of the cephalic vein, median vein and basilic vein were measured by B-ultrasound, and the three veins were evaluated and graded according to the grading criteria of superficial veins.The correlation between BMI and the subcutaneous depth and diameter of the three elbow veins was analyzed, and collected data such as puncture method and puncture times. Results:There was no significant correlation between BMI and subcutaneous depth and vessel diameter of the basilic vein ( r = 0.041 and 0.046, both P>0.05), the level of BMI was positively correlated with the subcutaneous depth and diameter of cephalic vein ( r = 0.275 and 0.117, both P<0.05) and median vein ( r = 0.236 and 0.148, both P<0.05), and a linear regression relationship was found ( OR values were 1.013-1.031, all P<0.05). 187 cases had direct puncture conditions under direct vision, and the success rate of one puncture was 86.63%(162/187).Venipuncture was completed under the guidance of B-mode ultrasound for 25 cases with failure under direct vision and 580 cases without direct puncture conditions under direct vision, the success rate of one puncture was 98.51% (596/605). Conclusions:With the increase of BMI level in patients with metabolic syndrome, the depth and diameter of both cephalic vein and median vein increase, venous exposure is difficult to express. The visual vein puncture guided by B-ultrasound is more accurate and catheterization is more reliable.

Nutrient Inputs Alleviate Negative Effects of Early and Subsequent Flooding on Growth of Polygonum hydropiper With the Aid of Adventitious Roots.

Riparian plants are exposed to harmful stress induced by flooding, which is often accompanied by eutrophication in the Three Gorges Reservoir Region. The phenomenon is mainly caused by domestic sewage discharges, slow water flow, and agricultural fertilizer pollution. Simulating abiotic stress, such as flooding at the initial period, can act as a signal and induce positive responses of plants to subsequent severe stress. In addition, eutrophication supplies nutrients, provides a favorable environment in the early stages of plant, and facilitates good performance in later development. However, whether early flooding (with or without eutrophication) acts as positive cue or as stress on plants at different developmental stages remains unclear. To address this question, seeds of Polygonum hydropiper were collected from low and high elevations in the hydro-fluctuation belt of the Three Gorges Reservoir Region. Plants germinated from these seeds were subjected to shallower and shorter early flooding treatments with or without eutrophication. Subsequently, plants were subjected to deeper and longer flooding treatments with or without eutrophication. Early flooding and eutrophic flooding significantly induced generation of adventitious roots, suggesting morphological adaptation to flooding. Although early flooding and eutrophic flooding treatments did not increase plant biomass in subsequent treatments compared with control, stem length, length and width of the 1st fully expanded leaf, and biomass of plants in the early eutrophic treatment were higher than these of the early flooding treatment plants. These results suggest a negative lag-effect of early flooding, and also indicate that nutrient inputs can alleviate such effects. Similarly, subsequent eutrophic flooding also enhanced plant growth compared with subsequent flooding, showing significantly higher values of leaf traits and adventitious root number. Plants originated from low elevation had significantly higher functional leaf length and stem biomass compared with those from high elevation. These results suggest that nutrient inputs can alleviate negative effects of early and subsequent flooding on growth of P. hydropiper with the generation of adventitious roots.

Sirtuin 1 alleviates microglia-induced inflammation by modulating the PGC-1α/Nrf2 pathway after traumatic brain injury in male rats.

Microglial activation and the subsequent inflammatory response play important roles in the central nervous system after traumatic brain injury (TBI). Activation of the PGC-1α pathway is responsible for microglial activation after TBI. Our previous study demonstrated that SIRT1 alleviates neuroinflammation-induced apoptosis after TBI, and activation of the PGC-1α/Nrf2 pathway extenuates TBI-induced neuronal apoptosis. However, no study has investigated whether SIRT1 can affect the PGC-1α/Nrf2 pathway to induce microglial excitation and the subsequent neuroinflammatory response. Microglial activation and the levels of pro-inflammatory factors, namely, tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were assessed to evaluate the neuroinflammatory response after TBI. To examine the effects of SIRT1, immunohistochemical staining and western blot analysis were used to observe the nuclear translocation and secretion of PGC-1α, as well as the activation of the PGC-1α/Nrf2 pathway. Treatment with the SIRT1 inhibitor sirtinol promoted microglial activation and pro-inflammatory factor expression (TNF-α, IL-6, and IL-1ß) and inhibited PGC-1α and Nrf2 nuclear translocation and secretion after TBI, while treatment with the SIRT1 activator A3 had the opposite effects. The results of this study suggest that microglial activation, the subsequent neuroinflammatory response, and the PGC-1α/Nrf2 pathway play essential roles in secondary injury after TBI. These results indicate that SIRT1 protects neurons after TBI by inhibiting microglial activation and the subsequent inflammatory response, possibly by activating the PGC-1α/Nrf2 pathway.

Inferring Postmortem Submersion Interval in Rats Found in Water Based on Vitreous Humor Metabolites / 法医学杂志

OBJECTIVES@#The metabolomics technique of LC-MS/MS combined with data analysis was used to detect changes and differences in metabolic profiles in the vitreous humor of early rat carcasses found in water, and to explore the feasibility of its use for early postmortem submersion interval (PMSI) estimation and the cause of death determination.@*METHODS@#The experimental model was established in natural lake water with 100 SD rats were randomly divided into a drowning group (n=50) and a postmortem (CO2 suffocation) immediately submersion group (n=50). Vitreous humor was extracted from 10 rats in each group at 0, 6, 12, 18 and 24 h postmortem for metabolomics analyses, of which 8 were used as the training set to build the model, and 2 were used as test set. PCA and PLS multivariate statistical analysis were performed to explore the differences in metabolic profiles among PMSI and causes of death in the training set samples. Then random forest (RF) algorithm was used to screen several biomarkers to establish a model.@*RESULTS@#PCA and PLS analysis showed that the metabolic profiles had time regularity, but no differences were found among different causes of death. Thirteen small molecule biomarkers with good temporal correlation were selected by RF algorithm. A simple PMSI estimation model was constructed based on this indicator set, and the data of the test samples showed the mean absolute error (MAE) of the model was 0.847 h.@*CONCLUSIONS@#The 13 metabolic markers screened in the vitreous humor of rat corpses in water had good correlations with the early PMSI. The simplified PMSI estimation model constructed by RF can be used to estimate the PMSI. Additionally, the metabolic profiles of vitreous humor cannot be used for early identification of cause of death in water carcasses.

A multicenter retrospective study of immunotherapy for metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.

The application of Hood technique in robotic-assisted radical prostatectomy / 中华泌尿外科杂志

Objective:To explore the feasibility, safety and short-term effect of the Hood technique in robotic-assisted radical prostatectomy (RARP).Methods:The data of 24 patients with localized prostate cancer underwent RARP with Hood technique From June 2020 to March 2021 were retrospectively reviewed. The mean age was 67.8 (57-76) years, and the mean body mass index was 25.17(18.31-32.54)kg/m 2. The mean tPSA value was 18.36(4.21-67.57)ng/ml and the mean biopsy Gleason score was 7.3 (6-8). In term of the clinical T stage, the 24 cases were composed of the T 1c stage in 1 case, T 2a stage in 5 cases, T 2b stage in 4 cases and T 2c stage in 14 cases. During Hood technique, the anterior bladder were limitedly isolated without exposing the outline of pelvis and prostate. Results:All the cases were completed robotically without conversion, transfusion or positive surgical margin. The average robot-assisted operation time was 84.5(63-110) mins. Estimated blood loss was 75.3(20-180) ml. The average time for maintaining the drain was 3.7(3-5) days. The mean postoperative hospital stay was 7.1(4-11) days. The mean catheterization time was 7.3(6-9) days after surgery. 23 patients achieved continence immediately after catheter removal, while 1 patient had continence full-recovery 2 weeks after surgery. The mean surgical Gleason score was 7.9 (6-9). In term of the surgical T stage, the 24 cases were composed of the pT 2a stage in 4 case, T 2b stage in 6 cases, T 2c stage in 14 cases.During 3-12 months’ follow-up, no biochemical recurrence was found. Conclusions:Hood technique were safe and valid in RARP with excellent immediate continence recovery. It facilitated Retzius sparing in a convenient approach with low positive surgical margin rate.

Preoperative Nomogram prediction model for lymph node metastasis in patients with renal cell carcinoma / 中华泌尿外科杂志

Objective:To identify preoperative clinical predictors of positive lymph nodes in patients with renal cell carcinoma (RCC)and provide a preoperative predictive model.Methods:The data of 173 RCC patients who underwent either retroperitoneal lymph node dissection or biopsy at a single institution from January 2016 to December 2020 were retrospectively analyzed. There were 109 males and 64 females, with an average age of (53.29±13.58) years, median tumor diameter of 70 (23-150) mm, 68 patients with local symptoms, 24 patients with systemic symptoms, and 56 patients with ECOG score ≥1. There were 96 patients with tumor pseudocapsule, 23 patients with renal vein or inferior vena cava tumor thrombus, 114 patients in stage T 1-2, 59 patients in stage T 3-4, 22 patients with distant metastasis and 88 patients with lymph node metastasis by preoperative imaging examination. Univariate analysis was performed by Mann-Whitney U test or Chi-square test, and multivariate logistic regression analysis was used to determine preoperative predictors of pathologic lymph node positivity. The significant variables were then included in a novel Nomogram to predict the probability of lymph node invasion.C-index and Bootstrap self-sampling methods were used to evaluate the discrimination and consistency of the model. Results:Of the 173 patients, 49(28.32%)and 124(71.68%)had pN 1 and pN 0 disease, respectively. Among 88 patients with suspected lymph node involvement (cN 1) assessed by preoperative imaging, only 47.73%(42/88) were confirmed to be pathologically positive. However, 8.24% (7/85) of the 85 patients with negative lymph nodes (cN 0) assessed by preoperative imaging were pathologically positive. Age, ECOG score, symptoms at presentation, tumor pseudocapsule, metastasis at diagnosis, clinical tumor stage, clinical nodal status, clinical nodal size, D-dimer, lactate dehydrogenase, microscopic hematuria were significant in the univariate analysis ( P<0.05). On multivariable analyses, the most informative independent predictors were age, clinical tumor stage, clinical nodal status, clinical nodal size and microscopic hematuria ( P<0.05). A Nomogram with good performance was developed to predict the probability of lymph node metastasis. The C-index of the model was 0.954, the calibration curve of forecasting curve with the ideal curve fit was good, indicating that the model has a good consistency. Conclusions:Younger age, microscopic hematuria, suspected lymph node involvement in imaging, larger lymph node diameter and higher T stage were independent risk factors for renal cell carcinoma with lymph node metastasis. The Nomogram based on the above factors has good identification and calibration ability, which can help predict the probability of lymph node metastasis of renal cell carcinoma before surgery.

Systematic Effect of Modified Renshen Wumeitang in Regulation of GABA Signaling Pathway in Rats with Diarrhea / 中国实验方剂学杂志

ObjectiveTo investigate the effect of modified Renshen Wumeitang（MRWT） on the related regulatory factors of the γ-aminobutyric acid （GABA） signaling pathway in colon tissues of rats with diarrhea， and reveal the mechanism of MRWT in invigorating Qi， generating fluid， and checking diarrhea. MethodForty-eight SD immature rats were randomly divided into a blank group （n=12） and an experimental group （n=36）. The diarrhea model was induced in the experimental group by Sennae Folium combined with overstrain and improper diet for 14 days. Subsequently， the model rats were randomly divided into a model group （normal saline， 20 mL·kg-1）， a western medicine group （Medilac-Vita， 0.7 g·kg-1）， and a Chinese medicine group （MRWT， 35 g·kg-1）， with 12 rats in each group. The rats in the blank group received normal saline at 20 mL·kg-1， and those in the other groups were treated correspondingly， once a day for 7 days. The general condition， loose stool rate， and diarrhea index of the rats were observed daily. Immunohistochemistry was used to detect the optical density expression of GABA protein in the colon of rats. The content of phosphatidylinositol-3 kinase （PI3K）， protein kinase B2 （Akt2）， phosphorylated Akt （p-Akt）， and interleukin-1β （IL-1β） was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PI3K， Akt2， and GABA type A receptor subunit β2 （GABRB2） in the colon of rats were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the blank group， the model group showed worsened general condition， The difference was not statistically significant of loose stool rate and diarrhea index， increased expression of GABA protein （P<0.05）， elevated expression of PI3K， Akt2， p-Akt， and IL-1β （P<0.05， P<0.01）， and up-regulated PI3K， Akt2， and GABRB2 mRNA and protein expression （P<0.01）. Compared with the model group， the western medicine group and the Chinese medicine group showed the improved general condition， decreased loose stool rate and diarrhea index （P<0.01）， and decreased content of PI3K， Akt2， p-Akt， and IL-1β （P<0.05）. The Chinese medicine group displayed decreased mRNA expression of PI3K， Akt2， and GABRB2 （P<0.05， P<0.01） and down-regulated protein expression of GABA， PI3K， and GABRB2 （P<0.05， P<0.01）. The western medicine group exhibited down-regulated mRNA expression of PI3K，Akt2，and protein of PI3K （P<0.05）. ConclusionMRWT can regulate the GABA signaling pathway， reduce Cl- flow in intestinal epithelial cells to the intestinal lumen， and improve the imbalance of colonic fluid metabolism in the colon of diarrhea rats， thereby exerting its effects of invigorating qi， generating fluid， and checking diarrhea.

Herbal Textual Research on Platycodonis Radix in Famous Classical Formulas / 中国实验方剂学杂志

In this paper， the name， origin， quality evaluation， producing area and processing methods of Platycodonis Radix used in the famous classical formulas are researched by consulting related materia medicas， prescription books and medical books of the past dynasties. It was found that Platycodonis Radix was the correct name in the materia medicas of the past dynasties， which was named for its "roots are strong but the stems are straight". Its dominant base of the past dynasties was Platycodon grandiflorus， and since the Ming and Qing dynasties， Hexian county of Anhui has been respected as the representative authentic producing area. In modern times， it has been concluded that the quality of Platycodonis Radix is best if the body is dry， thick and uniform， solid， white in color， and bitter in taste. In ancient times， the processing methods of Platycodonis Radix were mainly removing the reed head and floating skin， rice simmering and drying， and slicing and micro-frying. In modern times， its processing methods have been mainly simplified to peeling and cutting into thick slices. Therefore， it is recommended to use the dry roots of P. grandiflorus and its raw products in the famous classical formulas.

Genomic Epidemiology of Imported Cases of COVID-19 in Guangdong Province, China, October 2020 - May 2021 / 生物医学与环境科学（英文）

Objective@#The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated.@*Methods@#In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants.@*Results@#We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations.@*Conclusion@#These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.

Sirtuin 1 alleviates neuroinflammation-induced apoptosis after traumatic brain injury.

Sirtuin 1 (SIRT1) plays a very important role in a wide range of biological responses, such as metabolism, inflammation and cell apoptosis. Changes in the levels of SIRT1 have been detected in the brain after traumatic brain injury (TBI). Further, SIRT1 has shown a neuroprotective effect in some models of neuronal death; however, its role and working mechanisms are not well understood in the model of TBI. This study aimed to address this issue. SIRT1-specific inhibitor (sirtinol) and activator (A3) were introduced to explore the role of SIRT1 in cell apoptosis. Results of the study suggest that SIRT1 plays an important role in neuronal apoptosis after TBI by inhibiting NF-κB, IL-6 and TNF-α deacetylation and the apoptotic pathway sequentially, possibly by alleviating neuroinflammation.

Apoptosis-antagonizing transcription factor is involved in rat post-traumatic epilepsy pathogenesis.

The present study aimed to explore the pathogenesis behind post-traumatic epilepsy (PTE). In the present study, a chloride ferric injection-induced rat PTE model was established. The expression levels of apoptosis-antagonizing transcription factor (AATF), cleaved caspase-3, p53, Bcl-2 and Bax were measured by western blotting or immunofluorescence staining (IF). The expression of AATF in vivo was downregulated by microinjection of lentiviral-mediated short-hairpin RNA. Compared with control and sham groups, at day 5 after PTE, neuron apoptosis was significantly increased and the expression levels of AATF, p53, cleaved caspase-3 and Bax were significantly upregulated. In addition, IF revealed co-localization of AATF and cleaved caspase-3 in the cortex. Additionally, AATF was expressed mainly in neurons and astrocytes. Following AATF inhibition, the expression levels of p53 and cleaved caspase-3 were significantly reduced as compared with the control group. Taken together, these findings suggested that following PTE, AATF is involved in neuronal apoptosis and may serve as a potential target for its alleviation.

Effects of shenmai injection on postoperative delirium in patients undergoing off-pump coronary artery bypass graft / 中国医师杂志

Objective:To study the effects of shenmai injection on postoperative delirium (POD) in patients undergoing off-pump coronary artery bypass graft (OPCABG).Methods:40 patients undergoing OPCABG from September 2019 to March 2020 in Linyi People's Hospital were randomly divided into (group S) and control group (group C), 20 cases in each group. Shenmai injection (0.6 ml/kg)was diluted to 150 ml with 5% glucose in group S, and pumped through the central vein at the beginning of the operation. In the group C, at the beginning of the operation, 5% glucose injection (150 ml) was pumped through central vein. The values of ejection fraction (EF), cardiac output (CO), stroke volume (SV), stroke volume variation (SVV), bispectral index (BIS), oxygen partial pressure (PO 2), central venous oxygen saturation (ScVO 2) and lactic acid (LAC) at anesthesia induction (T 0), at the beginning of operation (T 1), at the beginning of coronary artery bypass graft (T 2), at the end of coronary artery bypass graft (CABG) (T 3), and at the end of operation (T 4) were recorded. Patients were evaluated for delirium on the 3rd and 7th day after surgery. Results:The EF, CO in the patients of group C and group S at T 2 were found to be significantly lower than those at T 0 ( P<0.05). The ScVO 2, PO 2 in the patients of group C and group S at T 4 were found to be significantly lower than those at T 0 ( P<0.05). The EF, CO and SV in the patients of group S at T 3 to T 4 were found to be significantly higher than those in group C ( P<0.05). The incidence of postoperative delirium on the third day in the group S was significantly lower than that in the group C ( P<0.05). Conclusions:Shenmai injection can improve the cardiac function and reduce the incidence of POD in patients with OPCABG.

Isomeric discrimination of kaempferol versus luteolin by online energy-resolved mass spectrometry / 中国中药杂志

Isomers are widely distributed in Chinese herbal medicines,and can be discriminated by energy-resolved mass spectrometry( ER-MS). However,ER-MS was performed through direct injection of reference compounds with syringe pump,which encountered a significant technical barrier for high-throughput and automated measurements. Herein,online ER-MS was conducted using LC-MS platform,and a pair of isomers,kaempferol vs luteolin,were employed as a case study to illustrate and assess the utility of online ER-MS for isomeric discrimination. High-resolution tandem mass spectrometry data of both flavonoids were acquired on LC-QE-Orbitrap-MS,and the fragmentation pathways responsible for the primary fragment ions were proposed. The primary signal in MS1 occurred at m/z 285( [M-H]-),and the primary signals of either compound generated by retro-Diels-Alder fragmentation were observed at m/z 151 and 133. The spectral information was subsequently transferred onto LC-Qtrap-MS platform to carry out online ER-MS. Two precursor-to-product ion transition candidates were constructed as m/z 285>151 and 285>133,and either afterward derived a set of pseudo-ion transitions( PITs) and so forth,exactly corresponding to a series of progressive collision energies( eg-5,-8,-11 e V,and so on). All PITs were typed into the monitoring list of multiple reaction monitoring program to generate the peak area datasets. Either dataset was normalized using the highest values in the set and imported into Graph Pad Prism software to plot the Gaus-sian-shaped curve that was termed as the break-down graph. The apex of the regressive curve was termed as optimal collision energy( OCE). The OCE values corresponding to m/z 285>151 were calculated as-29. 06 e V and-35. 71 e V for kaempferol and luteolin,respectively. In the case of m/z 285>133,the OCEs were yielded as-44. 15 e V for kaempferol and-49. 01 e V for luteolin. With re-ference to their chemical structures,the location of hydroxyl group was regarded to be responsible for the differences of either m/z 285>151 or 285>133 between the isomers,attributing to their different bond properties. Above all,online ER-MS offers an eligible tool for isomeric discrimination,and provides meaningful information for the accurate chemical composition characterization based on LC-MS,which is not limited to Chinese herbal medicines.