Progress in evaluating the risk of lymph node metastasis in early colorectal cancer / 中华胃肠外科杂志

Early colorectal cancers refer to invasive cancers that have infiltrated into the submucosa without invading muscularis propria, and approximately 10% of these patients have lymph node metastases that cannot be detected by conventional imaging. According to the guidelines of Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer, early colorectal cancer cases with risk factors for lymph node metastasis (poor tumor differentiation, lymphovascular invasion, deep submucosal invasion and high-grade tumor budding) should receive salvage radical surgical resection; however, the specificity of this risk-stratification is inadequate, making most patients undergo unnecessary surgery. Firstly, this review focuses on the definition, oncological impact importance and controversy of the above "risk factors". Then, we introduce the progress of the risk stratification system for lymph node metastasis in early colorectal cancer, including the identification of new pathological risk factors, the construction of new risk quantitative models based on pathological risk factors, artificial intelligence and machine learning technology and the discovery of novel molecular markers associated with lymph node metastasis based on gene test or liquid biopsy. Aim to enhance clinicians' understanding of the risk assessment of lymph node metastasis in early colorectal cancer; we suggest to take the patient's personal situation, tumor location, anti-cancer intention and other factors into account to make individualized treatment strategies.

Chinese expert consensus on emergency surgery for severe trauma and infection prevention during corona virus disease 2019 epidemic (version 2023) / 中华创伤杂志

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE-/-LDLR-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy in burn patients with sepsis / 中华烧伤杂志

Objective: To explore the value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy (SAE) in burn patients with sepsis. Methods: A retrospective case series study was conducted. From October 2018 to May 2021, 41 burn patients with sepsis who were admitted to Zhengzhou First People's Hospital met the inclusion criteria, including 23 males and 18 females, aged 18-65 (35±3) years. According to whether SAE occurred during hospitalization, the patients were divided into SAE group (21 cases) and non-SAE group (20 cases). The gender, age, deep partial-thickness burn area, full-thickness burn area, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores of patients were compared between the two groups. The serum levels of central nervous system specific protein S100β and neuron specific enolase (NSE) at 12, 24, and 48 h after sepsis diagnosis (hereinafter referred to as after diagnosis), the serum levels of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), Tau protein, adrenocorticotropic hormone (ACTH), and cortisol at 12, 24, 48, 72, 120, and 168 h after diagnosis, and the mean blood flow velocity of middle cerebral artery (VmMCA), pulsatility index, and cerebral blood flow index (CBFi) on 1, 3, and 7 d after diagnosis of patients in the two groups were counted. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. The independent variables to predict the occurrence of SAE was screened by multi-factor logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn for predicting the occurrence of SAE in burn patients with sepsis, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. Results: The gender, age, deep partial-thickness burn area, full-thickness burn area, and APACHE Ⅱ score of patients in the two groups were all similar (χ2=0.02, with t values of 0.71, 1.59, 0.91, and 1.07, respectively, P>0.05). At 12, 24, and 48 h after diagnosis, the serum levels of S100β and NSE of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 37.74, 77.84, 44.16, 22.51, 38.76, and 29.31, respectively, P<0.01). At 12, 24, 48, 72, 120, and 168 h after diagnosis, the serum levels of IL-10, Tau protein, and ACTH of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 10.68, 13.50, 10.59, 8.09, 7.17, 4.71, 5.51, 3.20, 3.61, 3.58, 3.28, 4.21, 5.91, 5.66, 4.98, 4.69, 4.78, and 2.97, respectively, P<0.01). At 12, 24, 48, 72, and 120 h after diagnosis, the serum levels of IL-6 and TNF-α of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 8.56, 7.32, 2.08, 2.53, 3.37, 4.44, 5.36, 5.35, 6.85, and 5.15, respectively, P<0.05 or P<0.01). At 12, 24, and 48 h after diagnosis, the serum level of cortisol of patients in SAE group was significantly higher than that in non-SAE group (with t values of 5.44, 5.46, and 3.55, respectively, P<0.01). On 1 d after diagnosis, the VmMCA and CBFi of patients in SAE group were significantly lower than those in non-SAE group (with t values of 2.94 and 2.67, respectively, P<0.05). On 1, 3, and 7 d after diagnosis, the pulsatile index of patients in SAE group was significantly higher than that in non-SAE group (with t values of 2.56, 3.20, and 3.12, respectively, P<0.05 or P<0.01). Serum IL-6 at 12 h after diagnosis, serum Tau protein at 24 h after diagnosis, serum ACTH at 24 h after diagnosis, and serum cortisol at 24 h after diagnosis were the independent risk factors for SAE complicated in burn patients with sepsis (with odds ratios of 2.42, 1.38, 4.29, and 4.19, 95% confidence interval of 1.76-3.82, 1.06-2.45, 1.37-6.68, and 3.32-8.79, respectively, P<0.01). For 41 burn patients with sepsis, the AUC of ROC of serum IL-6 at 12 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.84-1.00), the best threshold was 157 pg/mL, the sensitivity was 81%, and the specificity was 89%. The AUC of ROC of serum Tau protein at 24 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.82-1.00), the best threshold was 6.4 pg/mL, the sensitivity was 97%, and the specificity was 99%. The AUC of ROC of serum ACTH at 24 h after diagnosis for predicting SAE was 0.96 (95% confidence interval was 0.89-1.00), the best threshold was 14.7 pg/mL, the sensitivity was 90%, and the specificity was 94%. The AUC of ROC of serum cortisol at 24 h after diagnosis for predicting SAE was 0.93 (95% confidence interval was 0.86-1.00), the best threshold was 89 nmol/L, the sensitivity was 94%, and the specificity was 97%. Conclusions: Serum Tau protein, ACTH, and cortisol have high clinical diagnostic value for SAE complicated in burn patients with sepsis.

Preliminary observation on the differential expression of metformin in preventing noise-induced hearing loss in inner ear protein group of rats / 中华劳动卫生职业病杂志

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.

Comparison of Toric IOL alignment marking using Verion image guided system and conventional manual marker / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To compare the accuracy of Toric intraocular lens(IOL)alignment using the Verion image guided system and conventional manual marker. <p>METHODS:Prospective randomized controlled study. A total of 56 eyes of 47 age-related cataract patients who underwent phacoemulsification combined with Toric IOL implantation in our hospital from June 2016 to December 2019 were randomly divided into two groups:In the image-guided group, Verion navigation system collected anterior segmental images before surgery, and Toric target was set to 27 eyes in axial direction. In the marker group, Toric target was marked at 0° and 180° levels before surgery, and Toric target was marked in 29 eyes in axial direction according to the labeling ring. At 1h, 1wk, 1 and 3mo postoperatively, the anterior segment of patients with dilated pupil was photographed. Photoshop software was used to analyze the deviation between the actual axial direction and the target axial direction of the two groups, and the patients' naked eye visual acuity(UCDVA), best corrected visual acuity(BCDVA)and residual astigmatism were recorded. <p>RESULTS: At 1h and 3mo postoperatively, the deviation between the actual axis and the target axis of IOL in the navigation group was less than that in the marker group(1.5°±1.8° <i>vs</i> 3.1°±2.1°; 1.9°±1.6° <i>vs</i> 3.3°±2.4°, all <i>P</i><0.05). There was no difference in UCDVA(LogMAR)between the navigation group and the marker group(0.04±0.08 <i>vs</i> 0.06±0.07, <i>P</i>=0.338)and there was no difference in residual divergence(-0.39±0.32 <i>vs</i> -0.45±0.31D, <i>P</i>=0.491)between two groups at 3mo after operation.<p>CONCLUSION:Verion digital marking and manual marking showed high accuracy in marking Toric IOL axial direction. Although the navigation group showed no advantage in UCDVA and residual astigmatism, the IOL misalignment in navigation group was significantly smaller than the marker group, and Toric IOL axial direction was implanted more accurately under Verion digital marking.

From rural practice to national strategy for colorectal cancer screening in China--Mr. Zheng Shu who is a pioneer and practitioner / 中华胃肠外科杂志

Haining City and Jiashan County in Zhejiang Province are the first areas to carry out colorectal cancer screening in China, which started in the early 1970s and has been going on for more than 40 years. Meanwhile, Haining and Jiashan have also become the first batch of National Demonstration Bases for Early Diagnosis and Treatment of Colorectal Cancer. In the past 40 years, owing to Professor Zheng Shu who is brave and innovative, with an indomitable spirit, as well as the unremitting efforts and active exploration of all the team members, colorectal cancer screening which was unknown by the public and implemented with difficulties, has gradually been widely accepted and benefited the population. Today, remarkable achievements have been fulfilled in the colorectal cancer screening of Haining and Jiashan which has become the pioneer power in promoting the progress of colorectal cancer prevention and control in China and has certain influence both on China and the world. Meanwhile, a set of colorectal cancer screening strategies suitable for China has been explored and further promoted to be used nationwide, which is of great significance to the prevention and control of colorectal cancer in China. Looking forward to the future, the prevention and control of colorectal cancer in China is still difficult. We will continue to give full play to our existing advantages, not forget our original intention, move forward, explore innovation, and create greater glories!

Genetic analysis of three cases of acephalic spermatozoa syndrome caused by SUN5 mutation and the outcome of assisted reproductive technology / 北京大学学报(医学版)

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology. Clinical diagnosis, sperm morphology examination, sperm transmission electron microscopy examination were performed on 3 patients, and the whole exome sequencing technology was used for screening, Sanger sequencing verification, mutation pathogenicity analysis, and protein sequence homology comparison. Assisted reproductive technology was implemented to assist pregnancy treatment. The 3 patients were all sporadic infertile men, aged 25, 42 and 26 years, and there was no obvious abnormality in the general physical examination. Male external genitalia developed normally, bilateral testicles were normal in volume, and bilateral epididymis and spermatic vein were palpated without nodules, cysts, and tenderness. Repeated semen analysis showed that a large number of immature sperm could be seen, and they had the ability to move. The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T (p.Arg3Trp), a case of compound heterozygous missense mutation c.1067G>A (p.Arg356His) and nonsense mutation c.216G>A (p.Trp72*) and a case of homozygous missense mutation c.1043A>T (p.Asn348Ile), of which c.7C>T (p.Arg3Trp) and c.1067G>A (p.Arg356His) were new variants that had not been reported. SIFT, Mutation Taster and PolyPhen-2 software function prediction results were all harmful, the nonsense mutation c.216G>A (p.Trp72*) led to the premature termination of peptide chain synthesis which might have a greater impact on protein function. The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection, all of which were boys, and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations. Such patients could obtain their biological offspring through assisted reproductive technology. It was still necessary to pay attention to the genetic risk of ASS, it was recommended that both men and women conduct genetic counseling and screening at the same time. In clinical diagnosis, whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society. The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism, and at the same time expanded the pathogenic mutation spectrum of ASS.

A dose-response meta-analysis on the relationship between daily tea intake and cardiovascular mortality based on the GRADE system / 中华心血管病杂志

Objective: To explore the relationship between daily tea intake and cardiovascular disease (CVD) mortality. Methods: PubMed, EMbase, The Cochrane, Chinese Biomedical Literature Database, CNKI, and Wanfang Database were searched to collect research on tea intake and CVD mortality. The search period was from the establishment of the database to June 2020. Two researchers independently screened and extracted literature. The risk of bias was evaluated in the included studies, a dose-response meta-analysis was conducted, sensitivity analysis and publication bias analysis of the research results, and quality evaluation of the included literature and GRADE classification of the evidence body were performed. Results: A total of 21 cohort or case-control studies were included, including 1 304 978 subjects. Among them, 38 222 deaths from CVD were reported. The quality scores of the included studies were all ≥ 6 points. The dose-response meta-analysis showed that for every additional cup of tea intake per day, the mortality rate of CVD decreased by about 3% (95%CI 0.95-0.98, P<0.05), and there was a non-linear dose-response relationship (P<0.05). Compared with people who do not drink tea, people who drink 1 to 8 cups of tea a day have 8% lower CVD mortality (RR=0.92, 95%CI 0.89-0.95), 13% (RR=0.87, 95 %CI 0.84-0.91), 15% (RR=0.85, 95%CI 0.82-0.89), 15% (RR=0.85, 95%CI 0.81-0.89), 16% (RR=0.84, 95%CI 0.80-0.89), 16% (RR=0.84, 95%CI 0.81-0.88), 16% (RR=0.84, 95%CI 0.81-0.87), 16% (RR=0.84, 95%CI 0.80-0.88), respectively. The results of traditional meta-analysis showed that compared with people who do not drink tea, people who drink more than 1 cup of tea a day are associated with 14% lower CVD mortality rate (RR=0.86, 95%CI 0.81-0.91, I2=73.2%, P<0.05). The results of subgroup analysis showed that compared with the corresponding people who did not drink tea, men who drank more than 1 cup of tea a day reduced the CVD mortality rate by 24%, women by 14%, European and American populations by 12%, and Asian populations by 15%. The population who consumed green tea decreased CVD mortality by 15%, and the population of non-smokers decreased CVD mortality by 20% (all P<0.05). The population who consumed black tea decreased CVD mortality by 8%, and the smoking population who consumed black tea decreased CVD mortality by 3%, and the difference was not statistically significant (all P>0.05). The results of the bias analysis showed that Begg=0.42 and Egger=0.62, indicating that the distribution on both sides of the funnel chart is symmetrical, suggesting that there is no publication bias. The results of sensitivity analysis showed that the effect size of the outcome index did not change significantly after excluding any article, indicating that the results are robust and credible. The GRADE evaluation showed that the evidence grades of the outcome indicators were all low grade. Conclusions: Daily tea consumption is related to reduced CVD mortality. It is therefore recommended to drink an appropriate amount of tea daily.

Analysis of DNAH1 gene variant in two infertile males with multiple morphological abnormalities of sperm flagella / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease.@*METHODS@#Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variant analysis of the patients was conducted by using whole exome sequencing. Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis.@*RESULTS@#Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X) and c.6017T>G (p.V2006G). The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X), which were inherited from his father and mother, respectively. According to American College of Medical Genetics and Genomics standards and guidelines, the c.2016T>G (p.Y672X) and c.2610G>A (p.W870X) varaints of DNAH1 gene were predicted to be pathogenic (PVS1+PM2+PM3+PP3).@*CONCLUSION@#The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant, which has resulted in primary male infertility.

Protective Effect of Gentiopicroside Against Liver Injury in Mice via TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the mechanism of gentiopicroside （GPS） in preventing acute liver injury induced by carbon tetrachloride （CCl₄） in mice and its effect on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） signaling pathway. Method:Sixty mice were randomly divided into a normal control group， a model group， a silymarin group （150 mg·kg^-1）， and high- （200 mg·kg^-1）， medium- （100 mg·kg^-1）， and low-dose （50 mg·kg^-1） GPS groups， with 10 in each group. The mice in the groups with drug intervention were administered correspondingly by gavage at 10 mL·kg^-1， and those in the normal control group and the model group receive an equal volume of distilled water， once per day. Ten days after administration， mice in the normal control group were subjected to the intraperitoneal injection of peanut oil （10 mL·kg^-1） and those in other groups were injected with peanut oil （10 mL·kg^-1） containing 0.12% CCl₄for the induction of acute liver injury model. After fasting for 16 hours， blood was collected from eyeballs and liver tissues were collected. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of liver tissues. The content or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， alkaline phosphatase （ALP）， total superoxide dismutase （T-SOD）， and <italic>γ</italic>-glutamyl transpeptidase （<italic>γ</italic>-GT） in the serum， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） in liver tissues were determined by biochemistry techniques. The levels of tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， and interleukin-6 （IL-6） in liver tissues were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of TLR4， MyD88， and NF-<italic>κ</italic>B in liver tissues. The expression of phosphorylated NF-<italic>κ</italic>B （p-NF-<italic>κ</italic>B） was detected by immunohistochemistry. Result:Compared with the normal control group， the model group showed increased levels of ALT， AST， ALP， TBIL， <italic>γ</italic>-GT， and MDA （<italic>P</italic><0.01）， and blunted activities of T-SOD and GSH-Px （<italic>P</italic><0.01）. Compared with the model group， the high- and medium-dose GPS groups exhibited declining levels of ALT， AST， ALP， TBIL， <italic>γ</italic>-GT， and MDA （<italic>P</italic><0.05， <italic>P</italic><0.01） and potentiated T-SOD and GSH-Px activities （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the normal control group， the model group displayed elevated levels of TNF-<italic>α</italic>， IL-1<italic>β</italic>， and IL-6 in liver tissues （<italic>P</italic><0.01） and increased protein expression of TLR4， MyD88， and p-NF-<italic>κ</italic>B （<italic>P</italic><0.01）. Compared with the model group， the high- and medium-dose GPS groups showed decreased TNF-<italic>α</italic>， IL-1<italic>β</italic>， and IL-6 content in liver tissues （<italic>P</italic><0.05， <italic>P</italic><0.01） and dwindled TLR4， MyD88， and p-NF-<italic>κ</italic>B protein expression （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:GPS possesses a protective effect on mice with acute liver injury induced by CCl₄， and its mechanism of action may be related to the regulation of TLR4/MyD88/NF-<italic>κ</italic>B signaling pathway and inhibition of oxidative stress.

Esculetin protects against early sepsis via attenuating inflammation by inhibiting NF-κB and STAT1/STAT3 signaling / 中国天然药物

Esculetin, a natural derivative from the traditional and widely-used Chinese medicinal herb Cortex Fraxini, has a variety of pharmacological effects, especially in anti-inflammation. However, it is not clear whether esculetin has a therapeutic effect on sepsis. This study aimed to investigate the anti-inflammatory and protective effects of esculetin on early sepsis. The results showed that the lung injury was significantly relieved with the treatment of esculetin, accompanied with the restrained production of inflammatory factors including IL-1β, IL-6, TNF-α, CCL2 and iNOS during the early phase of E.coli-induced sepsis. Of note, activation of NF-κB and STAT1/STAT3 signals, the main upstream signals of many inflammatory factors, were attenuated by esculetin in both lung tissues from septic mice and LPS-stimulated macrophage. These findings suggested that the protection of esculetin against early sepsis should be related to its anti-inflammatory effect, which was at least partly due to its inhibition on NF-κB and STAT1/STAT3 signaling pathway in macrophage. Thus, esculetin could serve as a potential therapeutic agent by rebalancing innate immune response in macrophage for the treatment of early sepsis.

Anti-hemorrhoidal activity of Lian-Zhi-San, a traditional Chinese medicine, in an experimental hemorrhoidal model in rats / 中西医结合学报

OBJECTIVE@#Hemorrhoidal disease (HD) is the most common proctological disease, with an estimated prevalence rate of 4.4%, and a peak in individuals between 45 and 65 years of age. This study was done to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate the inflammatory injury, with its associated changes of inflammatory cytokines and morphology of anorectal tissues, in an experimental model of HD in rats.@*METHODS@#HD was induced by croton oil preparation (COP) applied to the anorectal region. Rats were then treated with cotton swabs soaked in LZS ointment, water or white vaseline, twice a day for 7 d. At the end of the experiment, HD was evaluated by measuring hemorrhoidal and biochemical parameters along with histopathological observations.@*RESULTS@#In this study, COP induced a significant increase in the macroscopic severity score, anorectal coefficient and Evans blue extravasation, compared to normal rats. Additionally, it greatly enhanced the expression and secretion levels of some important inflammation-related cytokines along with marked histological damage, compared to normal rats. Rats treated with LZS ointment experienced significantly ameliorated Evans blue extravasation (P < 0.05), decreased macroscopic severity score (0.86 ± 0.14 vs. 1.65 ± 0.16) and the anorectal coefficient (P < 0.01); its use also attenuated tissue damage and inhibited the expression and secretion levels of inflammation-related cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α).@*CONCLUSION@#This study validates a preliminary understanding of the use of LZS ointment to treat inflammatory factors and tissue damage in an experimental model of HD in rats.

Percutaneous transforaminal endoscopic foraminoplasty for simple lumbar spinal lateral exit-zone stenosis / 中国骨伤

OBJECTIVE@#To evaluate the clinical effects of percutaneous endoscopic foraminoplasty for simple lumbar spinal lateral exit zone stenosis.@*METHODS@#A total of 36 patients with simple lumbar spinal lateral exit zone stenosis were admitted to our hospital from January 2013 to June 2018, and received selective nerve root canal radiography and radicular block. According to the symptoms and patients' personal wills, 22 cases underwent the one-stage percutaneous foraminal surgery(the one-stage operation group), and the other 14 patients were re-admitted to the hospital for operation(the delayed operation group) because of the recurrence of symptoms after discharge. The visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the clinical effects before therapy, 1 day after the radicular block, and 1 day, 3 months and 6 months after the operation.@*RESULTS@#VAS and ODI of all 36 cases were obviously improved (0.05), but when compared with its own pretherapy andbefore readmission results, the difference was significant (<0.05). There was no nerve injury in all cases. Only 2 cases were presented with the outlet root stimulation symptoms, and the symptoms relieved after short term conservative treatment.@*CONCLUSION@#The clinical effects of radicular block may be unsustainable for patients with simple lumbar spinal lateral exit zone stenosis. Instead, percutaneous endoscopic foraminoplasty was simple, safe and effective.

Clinical effect of free anterolateral thigh flap in repairing large annular soft tissue defect of lower leg after burn / 中华烧伤杂志

Objective@#To explore the clinical effect of free anterolateral thigh flap in repairing large annular soft tissue defect of lower leg after burn.@*Methods@#From January 2014 to December 2018, 9 patients with large annular soft tissue defects of lower legs after burns were hospitalized in Zhengzhou First People′s Hospital, including 1 case with wounds on both legs. After debridement, area of wounds was 16 cm×11 cm-38 cm×21 cm, and the burn wounds were repaired with free anterolateral thigh flaps in the area of 18 cm×12 cm-32 cm×24 cm. End-to-end anastomosis of posterior tibial vessels or anterior tibial vessels with lateral circumflex femoral vessels was performed in manual way or by microvascular stapler. For the affected legs without condition for anastomosis, the sound medial lower leg flaps with areas of 10 cm×8 cm-15 cm×10 cm were excised and made into skin tubes, the posterior tibial vessels of the flaps were anastomosed with the vessels of free anterolateral femoral flaps, and the wounds of the injured lower legs were repaired by bridge-type cross-over free transplantation of anterolateral thigh flaps. The pedicles were broken 4 to 5 weeks later. The donor site was transplanted with autologous intermediate split-thickness skin graft from thigh. The outcome of the treatment, the number of perforators included in the flaps, and the anastomotic vessel in the recipient area of patients were recorded. The anastomosis time between manual way and microvascular staplers was recorded and compared. The patency of blood vessels, methods of free transplantation, and follow-up condition were recorded. Data were processed with Wilcoxon rank sum test for two independent samples.@*Results@#All the 10 free flaps and skin grafts of 9 patients survived, and all the wounds were closed by primary operation. Seven flaps contained two perforators each, and three flaps contained three perforators each. The anastomotic vessels were posterior tibial vessels in 6 recipient areas and anterior tibial vessels in 4 recipient areas. Microvascular stapler was used to anastomose 12 veins, while 8 veins and 10 arteries were anstomosed manually. The time consumed by the former method was 4.00 (3.55, 4.38) min, significantly shorter than 12.80 (12.13, 13.40) min of the latter (W=78.00, P<0.01). The patency rates of veins and arteries were 100%. There was no vascular crisis due to vascular anastomosis. Three patients underwent bridge-type cross-over free transplantation, while the others underwent conventional free transplantation. Follow-up for 3 to 30 months showed that the donor site of the thigh had good motor function, without numbness or pain, but hypertrophy of scar could be seen. Four patients had slightly overstaffed flaps transplanted in the recipient area of the lower legs, while the other patients were satisfied with their appearance, and the walking function of the affected limbs gradually recovered.@*Conclusions@#Free anterolateral thigh flap transplantation is a safe and reliable clinical limb salvage method for the repair of large annular soft tissue defect of lower leg after burn. Intraoperative application of microvascular stapler for venous anastomosis can shorten the time of vascular anastomosis and has great clinical application value.

Protective Effect and Mechanisms of Geraniin on D-galactosamine-induced Liver Injury in Mice / 中国实验方剂学杂志

Objective:To explore the hepatoprotective effect and its mechanism of the geraniin on mice with acute liver injury induced by D-galactosamine (D-GalN). Method:A total of 60 Kunming mice were randomly divided into normal group, model group, Silymarin group (positive group 180 mg·kg-1), and low, medium and high-dose geraniin groups (50, 100, 200 mg·kg-1). All the mice were given with saline or corresponding dose of drugs (10 mL·kg-1) by gavage once a day for 10 d. After 2 h of the last administration, except the normal group, the mice of other groups were injected intraperitoneally with D-GalN (500 mg·kg-1) to induce the acute liver injury. After 16 h, the eye balls of mice were removed to take blood, and all mice were put to death to collect samples of liver. Activity or content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in liver were determined by biochemical method. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-interferon (IFN-γ) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA), and expressions of Toll-like receptor-4(TLR-4) and nuclear factor(NF)-κB proteins were detected by Western blot. Liver histopathological changes were observed by hematoxylin-eosin (HE) staining. Result:Compared with the normal group, the serum levels of ALT, AST, ALP, TBIL and liver MDA in the model group were significantly increased (PPPPPPα, IL-1β, IL-6, IFN-γ and the expressions of TLR-4 and NF-κB proteins in serum (PPConclusion:Geraniin has an obvious protective effective on acute liver injuries induced by D-GalN in mice. Its mechanism may be correlated with oxidative stress, inflammation and TLR-4/NF-κB signaling pathway.

Protective Effect of Formula of Gougancat Decoction on Acute Liver Injury Induced by Carbon Tetrachloride in Rats / 中国实验方剂学杂志

Objective: To explore the protective effect of formula of Gougancai decoction (FGD) on acute liver injury induced by carbon tetrachloride (CCl4) in rats, in order to provide basis for the development of pharmaceutical preparations or healthcare products. Method: Sixty rats were randomly divided into normal group, Silymarin group (120 mg·kg-1) and FGD groups (475, 950, 1 900 mg·kg-1). The normal group and the model group were given equal volume of saline by gavage, while the other groups were administered with the corresponding dose of drugs according to the body weight. After 10 days, the acute liver injury model was established with 12% carbon tetrachloride peanut oil solution (5 mL·kg-1), except the normal group. All of the rats were put to death to collect serum and liver tissues. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected by biochemical methods, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in liver tissues were determined by enzyme-linked immunosorbnent assay(ELISA). Nuclear factor-κB (NF-κB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expression in liver tissues were detected by Western blot, and htoxylin eosin (HE) staining was used to observe the variation of liver histopathological. Result: Compared with the normal group, the serum activities of AST, ALT, ALP and the content of TBIL, MDA in the model group were significantly increased (Pα, IL-1β, IL-6 in liver tissue were remarkably increased (PPκB was enhanced in liver tissue (Pγ was down-regulated (PPPα, IL-1β, IL-6 (PPκB (PPγ (PPConclusion: FGD has a protective effect on CCl4-induced acute liver injury in rats, and its mechanism may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling pathway, with anti-inflammatory and anti-oxidative effects.

Effects of citric acid on patients with severe burn complicated with acute renal injury treated by continuous renal replacement therapy / 中华烧伤杂志

Objective@#To explore the effects of citric acid on patients with severe burn complicated with acute renal injury treated by continuous renal replacement therapy (CRRT).@*Methods@#Medical records of 83 patients with large area of burn complicated with acute renal injury admitted to intensive care unit (ICU) of our department from January 2015 to December 2018 and meeting the inclusion criteria were analyzed retrospectively. The patients were divided into heparin group [n=43, 25 males and 18 females, aged (35.0±2.5) years] and citric acid group [n=40, 22 males and 18 females, aged (37.0±6.6) years] according to different anticoagulation methods. After admission, routine support treatment and CRRT were performed after being diagnosed with acute renal injury in patients in 2 groups. Patients in heparin group were treated with low molecular weight heparin for anticoagulation with first dosage of 20 U/kg and an increase of 2.5 to 5.0 U per hour, and patients in citric acid group were given citric acid of 0.02 g/mL with dosage of 150~200 mL/h for anticoagulation. The use time of blood filter, recovery time of urine volume, and time of staying in ICU, and platelet count, activated partial thromboplastin time (APTT), prothrombin time (PT), and serum creatinine, urea nitrogen, cystatin C, procalcitonin, C-reactive protein, and neutrophil, leukocyte count, blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and heart rate, body temperature, and mean arterial pressure before treatment and post treatment hour (PTH) 24 were recorded. Besides, occurrence of hemorrhage, hypocalcemia, metabolic acidosis, metabolic alkalosis, and death within 28 days post injury were recorded. Data were processed with t test and chi-square test.@*Results@#The use time of blood filter of patients in citric acid group was (28.7±3.2)h, significantly longer than (19.4±2.6) h in heparin group (t=14.139, P<0.01). The recovery time of urine volume and time of staying in ICU of patients in citric acid group were respectively (7.6±0.9) and (9.6±1.3) d, significantly shorter than (9.2±1.5) and (11.2±1.8) d in heparin group (t=5.516, 4.697, P<0.01). Before treatment, there were no statistically significant differences in platelet count, APTT, and PT of patients in 2 groups (t=1.235, 0.515, 1.279, P>0.05). At PTH 24, the platelet count of patients in citric acid group was significantly higher than that in heparin group (t=10.947, P<0.01), and APTT and PT of patients in citric acid group were significantly shorter than those in heparin group (t=7.069, 9.142, P<0.01). Before treatment, there were no statistically significant differences in serum creatinine, urea nitrogen, and cystatin C of patients in 2 groups (t=1.684, 1.878, 1.472, P>0.05). At PTH 24, the serum creatinine, urea nitrogen, and cystatin C of patients in citric acid group were significantly lower than those in heparin group (t=7.778, 9.776, 5.117, P<0.01). Before treatment, there were no statistically significant differences in serum procalcitonin and C-reactive protein of patients in 2 groups (t=1.413, 0.898, P>0.05). At PTH 24, the serum procalcitonin and C-reactive protein of patients in citric acid group were significantly lower than those in heparin group (t=2.635, 2.297, P<0.05). Before treatment, there were no statistically significant differences in neutrophil, leukocyte count, blood sugar, AST, and ALT of patients in 2 groups (t=0.555, 0.816, 0.470, 1.896, 0.982, P>0.05). At PTH 24, the neutrophil, leukocyte count, blood sugar, AST, and ALT of patients in citric acid group were significantly lower than those in heparin group (t=2.054, 3.314, 7.185, 2.151, 3.013, P<0.05 or P<0.01). Before treatment, there were no statistically significant differences in heart rate, body temperature, and mean arterial pressure of patients in 2 groups (t=1.406, 0.474, 0.720, P>0.05). At PTH 24, the heart rate, body temperature, and mean arterial pressure of patients in citric acid group were significantly lower than those in heparin group (t=2.307, 4.498, 2.056, P<0.05 or P<0.01). The incidence of hemorrhage of patients in citric acid group while in hospital was significantly lower than that in heparin group (χ2=4.949, P<0.05). There were no statistically significant differences in incidence of hypocalcemia, metabolic acidosis, metabolic alkalosis, and death rate within 28 days post injury of patients in 2 groups while in hospital (χ2=3.346, 0.884, 0.297, 0.324, P>0.05).@*Conclusions@#Citric acid has significant anticoagulant effect on patients with large area of burn complicated with acute renal injury treated by CRRT, which can prolong the use time of the blood filter, shorten the recovery time of urine volume and time of staying in ICU, improve renal function indexes, blood biochemical indexes, and inflammation indexes, maintain the stability of internal environment, and reduce the risk of hemorrhage.

The intervention of ginkgo biloba extract on monocrotaline-induced right ventricular hypertrophy in rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To study the protective effects of ginkgo biloba extract on the right ventricular hypertrophy.@*METHODS@#Seventy-two SD male rats were randomly divided into 3 groups: control group(CON), monocrotaline-induced right ventricular hypertrophy group (MCT) and ginkgo biloba extract treated group (EGB) (n=24 in each group). Group MCT and group EGB were intraperitoneally injected with 2%MCT at the dose of 60 mg /kg on the first day. From the second day, group MCT was injected with 2 ml 0.9% sodium chloride, and 60 mg/kg ginkgo leaf extract was administered to the stomach in group EGB. The control group was injected with 2 ml 0.9% sodium chloride on the first day. After 3 weeks, in each group,cardiac hemodynamic changes were measured, heart weight index was calculated, and myocardial pathological changes were observed by HE staining. The expression of TRPC6 was detected by real-time polymerase chain reaction (real-time -PCR) and Western blot.@*RESULTS@#Compared with the control group, the right ventricular systolic pressure (RVSP) was increased significantly in the MCT group(P＜0.01), the maximum or decline rate of descent (RV ±dp/dt) of the right ventricle pressure was increased significantly(P＜0.01), while the EGB group had the same trend as all the indexes in the group MCT, but the amplitude of all indicators in group EGB were decreased significantly than those of group MCT(P＜0.01), and the right ventricular hypertrophy index (RVMI) in group EGB was significantly lower than that in group MCT(P＜0.01).Group MCT showed typical myocardial hypertrophy performance by HE staining, and the right ventricular myocytes in group EGB were significantly improved than that in group MCT, and the mRNA and protein expression levels of TRPC6 in the right ventricle of group MCT and group EGB were increased(P＜0.01), while the EGB group was significantly lower than that of the MCT group(P＜0.01).@*CONCLUSION@#Ginkgo biloba extract may inhibit the signal pathway of CaN / NFAT in cardiac myocytes by reducing the expression of TRPC6 protein, and then play an early protective effect on myocardial hypertrophy.