Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1Α pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.

Recent progress in the biosynthesis of dicarboxylic acids, a monomer of biodegradable plastics / 生物工程学报

Plastics are one of the most important polymers with huge global demand. However, the downsides of this polymer are that it is difficult to degrade, which causes huge pollution. The environmental-friendly bio-degradable plastics therefore could be an alternative and eventually fulfill the ever-growing demand from every aspect of the society. One of the building blocks of bio-degradable plastics is dicarboxylic acids, which have excellent biodegradability and numerous industrial applications. More importantly, dicarboxylic acid can be biologically synthesized. Herein, this review discusses the recent advance on the biosynthesis routes and metabolic engineering strategies of some of the typical dicarboxylic acids, in hope that it will help to provide inspiration to further efforts on the biosynthesis of dicarboxylic acids.

A comparative study of automatic delineation of organs at risk for prostate cancer based on deep learning and atlas library / 中华放射医学与防护杂志

Objective:To compare the effect of uPWS R15 software based on deep learning with MIM-Maestro 6.9 software based on atlas library to automatically delineate the organs at risk of prostate cancer in order to provide a reference for clinical application.Methods:The CT data of 90 prostate cancer patients admitted to the Department of Oncology Radiotherapy of the Affiliated Hospital of North Sichuan Medical College from 2018 to 2022 were retrospectively selected. Based on the uPWS R15 software developed by Shanghai United Imaging Medical Technology Company and the MIM-Maestro 6.9 software developed by Beijing Mingwei Vision Medical Software Company, the effects of uPWS and MIM software on automatic delineation of organs at risk were evaluated according to five parameters, including delineation time (T), Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), Hausdorff distance (HD) and the mean distance to agreement (MDA).Results:The sketching time of uPWS software was less than that of MIM software. There were no significant differences in the sketching effect of femoral head and skin between the two software (all P>0.05). The delineation of right kidney ( tMDA=-3.43, zDSC=-4.03, zJSC=-4.16, P<0.05), left kidney ( tMDA=-3.87, zDSC=-4.18, zJSC=-4.41, P<0.05), small intestine ( tMDA=-8.57, zDSC=-9.99, tJSC=14.21, P<0.05) and rectum ( zMDA=-4.00, tDSC=-9.98, tJSC= 9.72, P< 0.05) except HD, was statistically different. The bladder ( z=-7.88, -9.00, -8.17, -8.74, P<0.05) and spinalcord ( z=-3.87, -4.43, 4.03, 3.05, P<0.05) were also delineated with significant differences. The DSC automatically delineated by uPWS software was >0.7, while the DSC automatically delineated by MIM software was >0.7 for all other organs at risk except small intestine and rectum. In addition, the HD, MDA and JSC values of the organs at risk (bilateral femoral head, bilateral kidneys, spinal cord, bladder, skin, rectum and small intestine) automatically delineated by uPWS software were generally better than those with MIM software. Conclusions:The uPWS software outlines better than the MIM software, but the MIM software can also be used clinically with modifications to the small bowel and rectum, saving a great deal of time in preparation for radiation therapy.

Intraoperative assessment of blood supply to the femoral head after femoral neck fracture / 中华创伤骨科杂志

Objective:To explore intraoperative assessment of blood supply to the femoral head after femoral neck fracture, and the correlation between the blood supply and postoperative osteonecrosis of the femoral head.Methods:A retrospective analysis was performed of the 63 patients with femoral neck fracture who had been treated at Department of Orthopaedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University by open reduction and internal fixation with hollow compression screws from April 2016 to March 2021. They were 39 males and 24 females with an age of (44.9±13.6) years. There were 42 cases of Garden type Ⅲ and 21 cases of Garden type Ⅳ. Time from injury to operation was (4.1±2.4) days. After internal fixation, a hole was drilled using a 2.0 mm Kirschner wire at 2.0 cm above the femoral head-neck junction to observe the velocity, color, and characteristics of the blood oozing at the drill hole. The patients were divided into a good oozing group of 51 cases in whom bright red blood oozing was observed within 15 seconds after drilling and a poor oozing group of 12 cases in whom dark red blood oozing was observed beyond 15 seconds after drilling. The incidence of postoperative femoral head necrosis, Harris hip score, and visual analogue scale (VAS) for pain were compared between the 2 groups. Single factor and multi factor analyses were conducted using the Cox regression model to analyze the factors influencing postoperative femoral head necrosis in the patients.Results:The 63 patients were followed up for 24 (18, 36) months. The 2 groups were comparable because there was no significant difference in the preoperative general data between them ( P>0.05). Femoral head necrosis was observed in 3 cases in the good oozing group and in 5 cases in the poor oozing group, showing a significant difference between the 2 groups ( P<0.05). The Harris hip score [90.0 (86.0, 92.0)] and the VAS pain score [1.0 (1.0, 2.0)] at 1 year after surgery in the good oozing group were significantly better than those in the poor oozing group [85.5 (71.3, 88.8) and 2.5 (1.0, 3.8)] ( P<0.05). Multivariate Cox regression analysis showed that Garden type Ⅳ ( HR=6.784, 95% CI: 1.324 to 35.664, P=0.023) and intraoperative poor blood oozing ( HR=10.744, 95% CI: 2.359 to 51.774, P=0.003) were risk factors for femoral head necrosis after cannulated compression screw fixation of fractures of displaced femoral neck ( P<0.05). Conclusions:The blood supply to the femoral head after femoral neck fracture can be directly assessed by drilling a hole in the femoral head after open reduction and internal fixation. Intraoperative poor blood oozing is a risk factor for the femoral head necrosis after cannulated compression screw fixation of fractures of displaced femoral neck.

Progress in epidermal growth factor receptor-tyrosine kinase inhibitors-associated interstitial lung disease / 中国胸心血管外科临床杂志

@#The tyrosine kinase activity of epidermal growth factor receptor (EGFR) plays a key role in tumor cell proliferation, invasion, migration, and drug resistance. Studies have shown that non-small cell lung cancer patients with somatic driver gene EGFR mutations are sensitive to and can benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Nevertheless, EGFR-TKIs-related adverse events should not be ignored. Common adverse events such as diarrhea, acne-like rash and paronychia are usually manageable; although the incidence of interstitial lung disease is low, once it occurs, it is a serious threat to patients' life, and its pathogenesis is still unclear. There is very limited animal experimental and clinical research evidence on the potential mechanism of EGFR-TKIs-related interstitial lung disease in the available literature. Based on this, this article reviews the association between EGFR-TKIs and interstitial lung disease, at the same time, also discusses the research progress of EGFR-TKIs-related interstitial lung disease in combination with cytotoxic drugs or immunotherapeutic drugs and EGFR-TKIs, in order to provide a reference for the prevention and treatment of EGFR-TKIs-related interstitial lung disease in clinical practice in the future.

Clinical characteristics and risk factors for perioperative lung surgery patients with SARS‐CoV‐2 infection / 中国胸心血管外科临床杂志

@#Objective     To investigate the clinical characteristics and risk factors for perioperative lung surgery patients with SARS‐CoV‐2 Omicron variant infection. Methods     The clinical data of patients who underwent lung surgery at the Department of Thoracic Surgery, Renmin Hospital of Wuhan University from December 1, 2022 to January 9, 2023 were retrospectively analyzed. The patients were divided into an infection group and a non-infection group according to whether they were infected with SARS-CoV-2. And the clinical data of two groups were collected and compared. Multiple linear regression analysis was used to explore the risk factors affecting the time of hospitalization. Results     A total of 70 patients were enrolled in this study, including 36 (51.4%) males and 34 (48.6%) females at a median age of 61.0 (49.0, 66.8) years. There were 28 patients in the infection group and 42 patients in the non-infection group. The proportion of preoperative abnormal coagulation function and the risk of postoperative pulmonary infection in perioperative patients infected with SARS-CoV-2 were higher than those in the non-infection group (P<0.05). Subgroup analysis found that patients with preoperative SARS-CoV-2 infection were more likely to have pulmonary infection after surgery, but did not prolong the time of hospitalization or increase the risk of severe disease rate. The patients with postoperative SARS-CoV-2 infection had worse clinical prognosis, including longer time of hospitalization (P=0.004), higher ICU admission rate (P=0.000), higher lung infection rate (P=0.003) and respiratory failure rate (P=0.000). Multiple linear regression analysis showed that gender and extent of surgery were independent risk factors for prolonged hospitalization time. Conclusion     Preoperative infection with SARS-CoV-2 Omicron variant will increase the risk of pulmonary infection, but it will not affect the clinical prognosis. However, postoperative infection with SARS-CoV-2 Omicron variant will still prolong the time of hospitalization, increase the ICU rate, and the risk of pulmonary complications.

Analysis of intermittent photic stimulation in children′s video electroencephalography / 中华实用儿科临床杂志

Objective:To explore the value of intermittent photic stimulation (IPS) in children′s video electroencephalography (EEG).Methods:The data of 8 994 children aged 1 to 18 years, who received IPS in the video EEG examination at the Liangjiang Campus of the Children′s Hospital of Chongqing Medical University from March 2021 to March 2022, were analyzed retrospectively.Patients were divided into non-epilepsy group and confirmed or suspected epilepsy group.Their IPS responses, clinical and EEG characteristics were collected.Categorical variables were expressed using frequencies and percentages.The relationship between IPS response and age was determined by Chi- square test or Fisher′ s exact probability method. Results:The median age of 8 994 children was 6.3 years.There were 2 310 (25.7%) children in the non-epileptic group, including 1 364 (59.0%) males and 946 (41.0%) females.There were 6 684 (74.3%) children in the confirmed or suspected epileptic group, including 3 842 (57.5%) males and 2 842 (42.5%) females.In the non-epileptic group, 141 cases (6.1%) had IPS photo-driving responses, and 1 case had photo paroxysmal response (PPR). In the confirmed or suspected epilepsy group, IPS photo-driving responses (2.4%) occurred in 160 cases, PPR (1.2%) in 82 cases, photo convulsion responses(0.3%) in 18 cases, and asymmetric photo-driving responses (0.2%) in 14 cases.The IPS photosensitivity responses varied among children of different ages, sexes, epileptic discharge types and seizure types in the confirmed or suspected epilepsy group.The children aged 6 to 18 years showed significantly stronger photosensitivity responses than those aged 1 to <6 years ( P<0.001). The photosensitivity activity in females was 1.9 times higher than that in males.The photosensitivity activity in patients with generalized discharges was 1.7 times more intense than that in patients with focal discharges.The photosensitivity reaction in patients with photo convulsive generalized seizures was 2.5 times stronger than that in patients with focal seizures. Conclusions:Routine standardized IPS is important for the detection of photosensitivity in children diagnosed or suspected with epilepsy.It can effectively guide the medical practice.

Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer / 中华胃肠外科杂志

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

Anatomical and histological investigation of the area anterior to the anorectum passing through the levator hiatus / 中华胃肠外科杂志

Objective: To document the anatomical structure of the area anterior to the anorectum passing through the levator hiatus between the levator ani slings bilaterally. Methods: Three male hemipelvises were examined at the Laboratory of Clinical Applied Anatomy, Fujian Medical University. (1) The anatomical assessment was performed in three ways; namely, by abdominal followed by perineal dissection, by examining serial cross-sections, and by examining median sagittal sections. (2) The series was stained with hematoxylin and eosin to enable identification of nerves, vessels, and smooth and striated muscles. Results: (1) It was found that the rectourethralis muscle is closest to the deep transverse perineal muscle where the longitudinal muscle of the rectum extends into the posteroinferior area of the membranous urethra. The communicating branches of the neurovascular bundle (NVB) were identified at the posterior edge of the rectourethralis muscle on both sides. The rectum was found to be fixed to the membranous urethra through the rectourethral muscle, contributing to the anorectal angle of the anterior rectal wall. (2) Serial cross-sections from the anal to the oral side were examined. At the level of the external anal sphincter, the longitudinal muscle of the rectum was found to extend caudally and divide into two muscle bundles on the oral side of the external anal sphincter. One of these muscle bundles angled dorsally and caudally, forming the conjoined longitudinal muscle, which was found to insert into the intersphincteric space (between the internal and external anal sphincters). The other muscle bundle angled ventrally and caudally, filling the gap between the external anal sphincter and the bulbocavernosus muscle, forming the perineal body. At the level of the superficial transverse perineal muscle, this small muscle bundle headed laterally and intertwined with the longitudinal muscle in the region of the perineal body. At the level of the rectourethralis and deep transverse perineal muscle, the external urethral sphincter was found to occupy an almost completely circular space along the membranous part of the urethra. The dorsal part of the external urethral sphincter was found to be thin at the point of attachment of the rectourethralis muscle, the ventral part of the longitudinal muscle of the rectum. We identified a venous plexus from the NVB located close to the oral and ventral side of the deep transverse perineal muscle. Many vascular branches from the NVB were found to be penetrating the longitudinal muscle and the ventral part of rectourethralis muscle at the level of the apex of the prostate. The rectourethral muscle was wrapped ventrally around the membranous urethra and apex of the prostate. The boundary between the longitudinal muscle and prostate gradually became more distinct, being located at the anterior end of the transabdominal dissection plane. (3) Histological examination showed that the dorsal part of the external urethral sphincter (striated muscle) is thin adjacent to the striated muscle fibers from the deep transverse perineal muscle and the NVB dorsally and close by. The rectourethral muscle was found to fill the space created by the internal anal sphincter, deep transverse perineal muscle, and both levator ani muscles. Many tortuous vessels and tiny nerve fibers from the NVB were identified penetrating the muscle fibers of the deep transverse perineal and rectourethral muscles. The structure of the superficial transverse perineal muscle was typical of striated muscle. These findings were reconstructed three-dimensionally. Conclusions: In intersphincteric resection or abdominoperineal resection for very low rectal cancer, the anterior dissection plane behind Denonvilliers' fascia disappears at the level of the apex of the prostate. The prostate and both NVBs should be used as landmarks during transanal dissection of the non-surgical plane. The rectourethralis muscle should be divided near the rectum side unless tumor involvement is suspected. The superficial and deep transverse perineal muscles, as well as their supplied vessels and nerve fibers from the NVB. In addition, the cutting direction should be adjusted according to the anorectal angle to minimize urethral injury.

Uniportal thoracoscopic thorough debridement for tubercular empyema with abscess of the chest wall / 中华外科杂志

Objective: To examine the feasibility and technical considerations of thorough debridement using uniportal thoracoscopic surgery for tuberculous empyema complicated by chest wall tuberculosis. Methods: A retrospective analysis was conducted on 38 patients who underwent comprehensive uniportal thoracoscopy debridement for empyema complicated by chest wall tuberculosis in the Department of Thoracic Surgery, Shanghai Pulmonary Hospital, from March 2019 to August 2021. There were 23 males and 15 females, aged (M(IQR)) 30 (25) years (range: 18 to 78 years). The patients were cleared of chest wall tuberculosis under general anesthesia and underwent an incision through the intercostal sinus, followed by the whole fiberboard decortication method. Chest tube drainage was used for pleural cavity disease and negative pressure drainage for chest wall tuberculosis with SB tube, and without muscle flap filling and pressure bandaging. If there was no air leakage, the chest tube was removed first, followed by the removal of the SB tube after 2 to 7 days if there was no obvious residual cavity on the CT scan. The patients were followed up in outpatient clinics and by telephone until October 2022. Results: The operation time was 2.0 (1.5) h (range: 1 to 5 h), and blood loss during the operation was 100 (175) ml (range: 100 to 1 200 ml). The most common postoperative complication was prolonged air leak, with an incidence rate of 81.6% (31/38). The postoperative drainage time of the chest tube was 14 (12) days (range: 2 to 31 days) and the postoperative drainage time of the SB tube was 21 (14) days (range: 4 to 40 days). The follow-up time was 25 (11) months (range: 13 to 42 months). All patients had primary healing of their incisions and there was no tuberculosis recurrence during the follow-up period. Conclusion: Uniportal thoracoscopic thorough debridement combined with postoperative standardized antituberculosis treatment is safe and feasible for the treatment of tuberculous empyema with chest wall tuberculosis, which could achieve a good long-term recovery effect.

Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1 / 中国结合医学杂志

OBJECTIVE@#To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.@*METHODS@#Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).@*RESULTS@#DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.@*CONCLUSION@#CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.

Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL).@*METHODS@#The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS.@*RESULTS@#The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high β2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL.@*CONCLUSION@#Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.

Clinical controversy and research thoughts on lymphadenectomy of gastric cancer / 中华胃肠外科杂志

Lymphadenectomy, as one of the controversial foci in clinic, is an extremely important part of radical surgery for gastric cancer. So far, the preliminary consensus has been reached on the scope and number of lymph node dissection, based on the etiological mechanism, disease progression, diagnosis and treatment prognosis of gastric cancer. At present, some clinical issues of lymphadenectomy in curative gastrectomy are still need to be addressed. Firstly, standardized procedure in lymph node dissection for gastric cancer is a prerequisite to decrease the incidence of postoperative complications and to improve the prognosis of gastric cancer patients. Furthermore, the plausible treatment strategy in perioperative phase is also deemed as the other key method to offer a benefit of survival rate for advanced stage patients after lymphadenectomy. Last but not least, the technologies for enhancement the prediction accuracy of lymph node metastasis preoperatively or intraoperatively should be worthy in-depth study.

OCTA changes in blood flow density of patients with Alzheimer's disease: a Meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the changes of retinal optical coherence tomography angiography(OCTA)vessel density in Patients with Alzheimer's disease(AD)by Meta-analysis, and to explore the value of OCTA in early diagnosis of AD patients.<p>METHODS: Embase, PubMed and Cochrane Library data were searched from January 2016 to September 2021 for relevant studies on vessel density in macular area of AD patients. Two researchers independently screened the literature, extracted the data, and evaluated the risk of inclusion bias using Newcastle-Ottawa Scale(NOS). Meta-analysis was performed using RevMan 5.3 software.<p>RESULTS: A total of 740 cases(eyes)were included in 10 literatures, including 321 cases from the AD group and 419 cases from the control group(age-matched people with normal cognitive abilities). The results of the Meta-analysis showed that the superficial vessel density in macular area of AD patients was lower than that in control group(<i>MD</i>=-1.58, 95%<i>CI</i> -2.60- -0.55, <i>P</i>=0.003). The deep vessel density in macular area of AD patients was lower than that in control group(<i>MD</i>=-2.72, 95%<i>CI</i> -4.36- -1.07, <i>P</i>=0.001). The parafoveal vessel density in AD patients was lower than that in control group(<i>MD</i>=-1.44, 95%<i>CI</i> -1.94- -0.94, <i>P</i><0.00001). The avascular area in the fovea of AD patients was slightly larger than that of the control group(<i>MD</i>=0.05, 95%<i>CI</i> -0.01-0.11, <i>P</i>=0.13).<p>CONCLUSION: The vessel density of each layer in macular area of AD patients were lower than that of control groups the difference was statistically significant. OCTA can assist in the early diagnosis of AD.

Interpretation of the second update to the ninth edition of antithrombotic therapy guidelines for venous thromboembolism disease published by American College of Chest Physicians / 中国胸心血管外科临床杂志

@#Venous thromboembolism (VTE), comprising both deep vein thrombosis and pulmonary embolism, is a chronic illness that contributes significantly to the global burden of disease. The American College of Chest Physicians (ACCP) published the 9th edition of antithrombotic treatment guidelines for VTE (AT9) in 2012, which was first updated in 2016. In October 2021, ACCP published the 2nd update to AT9, which addressed 17 clinical questions related to VTE and presented 29 guidance statements in total. In this paper we interpreted the recommendations proposed in this update of the guidelines.

Engineering Saccharomyces cerevisiae for efficient production of glucaric acid / 生物工程学报

As an important dicarboxylic acids existing in nature, glucaric acid has been widely used in medical, health, and polymer materials industry, therefore it is considered as one of the "top value-added chemicals from biomass". In this study, using Saccharomyces cerevisiae as a chassis microorganism, the effects of overexpression of myo-inositol transporter Itr1, fusional expression of inositol oxygenase MIOX4 and uronate dehydrogenase Udh, and down-expression of glucose-6-phosphate dehydrogenase gene ZWF1 on the glucaric acid production were investigated. The results showed that the yield of glucaric acid was increased by 26% compared with the original strain Bga-3 under shake flask fermentation after overexpressing myo-inositol transporter Itr1. The yield of glucaric acid was increased by 40% compared with Bga-3 strain by expressing the MIOX4-Udh fusion protein. On these basis, the production of glucaric acid reached 5.5 g/L, which was 60% higher than that of Bga-3 strain. In a 5 L fermenter, the highest yield of glucaric acid was 10.85 g/L, which was increased 80% compared with that of Bga-3 strain. The application of the above metabolic engineering strategy improved the pathway efficiency and the yield of glucaric acid, which may serve as a reference for engineering S. cerevisiae to produce other chemicals.

Analysis of acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack based on complex network / 中国针灸

Acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack was analyzed based on complex network, acupoint names and indications were extracted from the book, which provided ideas and methods for promoting the modernization of acupuncture and moxibustion by using complex network technology. A total of 112 acupoints in 201 acupuncture prescriptions were included, and the total frequency of acupoints was 880 times, forming 42 034 acupoint pairs. In terms of network indexes, compared with the complex network of comprehensive acupuncture books, such as Meridian and Acupoint Science, Zhenjiu Dacheng, Acupuncture A and B Meridians formed based on the same mathematical method, the complex network model for CHENG Dan-an's Note About Treatise on Cold-Attack shows more typical small world effect, which is characterized by higher network density (6.762) and shorter average path length (1.064). This phenomenon may be related to the tongue and pulse which added the link between acupoints. For the node indexes, the analysis of topological indexes such as Page Rank shows that acupoints represented by Dazhui (GV 14) has higher compatibility value in the treatment of exogenous diseases, which further demonstrates the clinical value of eigenvector centrality in guiding intelligent compatibility of points.

Pharmacological Effect and Mechanism of Andrographolide： A Review / 中国实验方剂学杂志

Andrographolide， a diterpene lactone， is the important material basis for the pharmacological effect of the Chinese medicinal Andrographis paniculata （Burm.f.）Nees. Modern pharmacological research has shown that andrographolide has many pharmacological activities such as anti-inflammation， bacteriostat， anti-virus， anti-tumor， protecting liver， promoting the function of gallbladder， and protecting the cardiovascular system and nervous system. It has significant anti-inflammatory activity which involves multiple targets. To be specific， it can inhibit nuclear factor-κB （NF-κB）， signal transduction and activator of transcription 3 （STAT3）， and other signaling pathways， reduce the synthesis and release of downstream inflammatory mediators， and regulate oxidative stress and immune response to achieve anti-inflammatory effect on various inflammatory diseases. At the same time， it suppresses a variety of tumor cells by inhibiting tumor cell proliferation， blocking cell cycle， and inducing tumor cell apoptosis. Its anti-tumor mechanism involves cellular signaling pathways such as Notch， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， NF-κB， and secreted glycoprotein/β-catenin （Wnt/β-catenin）. In addition， it can also alleviate diabetes by regulating glucose metabolism. According to related research， it often exerts pharmacological effects through multiple pathways and multiple targets， but the specific targets are unclear. Therefore， this article summarizes the relevant studies on the pharmacological effects and mechanisms of andrographolide in the past three years and puts forward the future research directions， which is expected to serve as a reference for the further in-depth research and development and utilization of andrographolide.

Anti-tumor Effect of Shikonin： A Review / 中国实验方剂学杂志

The incidence and mortality of cancer are increasing year by year， seriously threatening human health. At present， the chemotherapy-based treatment of cancer can prolong the survival time of patients， but its severe side effects and adverse reactions often lead to poor prognosis. Therefore， searching for anti-cancer drugs with high efficiency and low toxicity has become the focus of clinical attention from all over the world. The effective components of Chinese medicine have the advantages of mild side effect and multi-target regulation， and their anti-tumor activities are highly favored by many researchers. Shikonin， a naphthoquinone compound， is the main effective component of Arnebiae Radix， with anti-tumor， anti-inflammatory， antioxidant， and other pharmacological effect. Studies have shown that shikonin possesses significant anti-tumor activities against a variety of tumor cells， and it can inhibit the development of many cancers， such as breast cancer， lung cancer， liver cancer， cervical cancer， ovarian cancer， colon cancer， and prostate cancer. The anti-tumor mechanism of shikonin is mainly related to multi-pathway and multi-target inhibition of tumor cell proliferation， the promotion of reactive oxygen species （ROS） production， induction of tumor cell apoptosis， cell cycle arrest， and tumor cell autophagy， and the inhibition of tumor cell migration and invasion. In addition， shikonin can increase the sensitivity of tumor cells to anti-tumor drugs and reverse the drug resistance of tumor cells. The signaling pathways involved in the anti-tumor effect of shikonin include phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， PI3K/Akt/mammalian target of rapamycin （mTOR）， mitogen-activated protein kinase （MAPK）， pyruvate kinase M2/signal transducer and activator of transcription protein 3 （PKM2/STAT3）， and Kelch-like epichlorohydrin-related protein 1/nuclear factor E2-related factor 2 （Keap1/Nrf2）. The anti-tumor effects are mainly achieved through the regulation of the PI3K/Akt signaling pathway. Based on the relevant literature on the anti-tumor effect and mechanism of shikonin in China and abroad， the present study reviewed the research progress in the past three years to provide useful references for the further study of the anti-tumor effect of shikonin and the research and development of new antineoplastic drugs.

Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61 / 中西医结合学报

OBJECTIVE@#Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.@*METHODS@#The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.@*RESULTS@#Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.@*CONCLUSION@#The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.