The efficacy of da Vinci robot-assisted lobectomy versus segmentectomy for stage ⅠA non-small cell lung cancer: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To compare and analyze the therapeutic effects of robot-assisted lobectomy and segmentectomy for stage ⅠA non-small cell lung cancer with a diameter≤2 cm. Methods    A total of 181 patients with pathologically confirmed stage ⅠA non-small cell lung cancer (diameter≤2 cm) who underwent robot-assisted lobectomy and segmentectomy in our hospital from 2018 to 2021 were included. There were 74 males and 107 females with an average age of 57.50±10.60 years. They were divided into two groups according to the surgical procedure: a segmentectomy group (85 patients) and a lobectomy group (96 patients). Results    There was no statistically significant  difference between the two groups in terms of clinical data such as age, gender, smoking history, basic disease, pathological type, tumour diameter, operative time, postoperative 24 h drainage volume and overall complications (P>0.05). The intraoperative blood loss (33.88±16.26 mL vs. 39.27±19.48 mL, P=0.046), groups of dissected lymph nodes (4.76±1.19 vs. 5.52±1.46, P=0.000), number of dissected lymph nodes (14.81±7.23 vs. 18.06±7.70, P=0.004) and postoperative 72 h drainage volume (561.65±225.31 mL vs. 649.84±324.34 mL, P=0.037) of patients in the segmentectomy were less than those in the lobectomy group. The chest drainage time (5.49±3.92 d vs. 7.60±4.96 d, P=0.002) and postoperative hospital stay time (7.47±4.16 d vs. 9.67±5.50 d, P=0.003) were shorter than those in the lobectomy group. There was no conversion to thoracotomy or perioperative death in the two groups. The postoperative follow-up rate was 100.0% with a longest follow-up time of 48 months. The 3-year recurrence-free survival rates of the segmentectomy group and lobectomy group were 87.7% and 92.4%, respectively (P=0.465). Conclusion    The da Vinci robot-assisted lobectomy and segmentectomy are safe and feasible surgical procedures for patients with stage ⅠA non-small cell lung cancer (diameter≤2 cm), with a similar 3-year recurrence-free survival rate. The lobectomy group has more lymph nodes dissected, while the segmentectomy group is superior to the lobectomy group in terms of intraoperative blood loss, postoperative 72 h chest drainage volume, chest drainage time and postoperative hospitalization time.

Complex treatment of neuromuscular diseases in PICU / 中国小儿急救医学

Neuromuscular diseases are a group of disorders that affect the anterior horn cells of the spinal cord, peripheral nerves, neuromuscular junction and skeletal muscle.A subset of children with neuromuscular disease have rapidly progressive conditions that threaten respiratory and medulla oblongata function.The main causes of neuromuscular disease in PICU include severe neurological impairment, infections, comorbidities, unexpected situations, and other conditions that can exacerbate the primary disease.In each case, timely identification and development of the specific therapies and supportive care measures could improve prognosis.

Clinical features of three children with severe COVID-19 encephalopathy and literature review / 中国小儿急救医学

Objective:To analyze the clinical characteristics, diagnosis and treatment of 3 children with severe COVID-19 encephalopathy, aiming to improve the clinicians′ understanding of the disease.Methods:The clinical features, laboratory examinations, imaging data and diagnosis as well as treatment process of 3 cases of severe COVID-19 encephalopathy admitted to the Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University from December 1, 2022 to December 31, 2022 were retrospectively analyzed.Results:Among the 3 patients, 2 were female, age was 2-11 years old, all of them had 2-3 days of medical history.All of them had clinical manifestations of high fever(≥40 ℃), convulsions and consciousness disorders, nucleic acid and antigen tests of SARS-CoV-2 were positive, and mycoplasma pneumonia IgM antibody was positive in 1 case.Within 24 hours after admission, the levels of white blood cells were basically normal, neutrophil fraction was dominant, and procalcitonin was significantly increased.Total T cells and NK cells in the blood of the three patients were significantly decreased, and the levels of blood ammonia, blood glucose and bilirubin were basically normal.During the early stage of the disease, the cell counts of the cerebrospinal fluid was normal in all three patients, the protein level was significantly increased, and there were new symmetrical lesions on head magnetic resonance imaging in 3 patients.After symptomatic treatment and immunotherapy including early use of hormone, human gamma globulin and plasma exchange, all patients were survived, but had different degrees of new dysfunction of the nervous system.Conclusion:Severe COVID-19 encephalopathy can occur in the acute phase of SARS-CoV-2 infection, mostly manifested as high fever, convulsions and severe disturbance of consciousness, combining with multiple organ dysfunction and irreversible nervous system damage.Early supportive treatment, brain protective treatment and immunotherapy are helpful to improve the prognosis of the patients.

Clinical features of three children with severe COVID-19 encephalopathy and literature review / 中国小儿急救医学

Objective:To analyze the clinical characteristics, diagnosis and treatment of 3 children with severe COVID-19 encephalopathy, targeted to improve the clinicians′ understanding of the disease.Methods:The clinical features, laboratory examinations, imaging data and diagnosis and treatment process of 3 cases of severe COVID-19 encephalopathy admitted to the Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University from December 1, 2022 to December 31, 2022 were retrospectively analyzed.Results:Among the 3 patients, 2 were female, age was 2-11 years old, all of them had 2-3 days of medical history, all of them had clinical manifestations of high fever(≥40 ℃), convulsions and consciousness disorders, nucleic acid and antigen tests of SARS-CoV-2 were positive, and mycoplasma pneumonia IgM antibody was positive in 1 case.Within 24 hours after admission, the levels of white blood cells were basically normal, neutrophil fraction was dominant, and procalcitonin was significantly increased.Total T cells and NK cells in the blood of the three patients were significantly decreased, and the levels of blood ammonia, blood glucose and bilirubin were basically normal.In the early stage of the disease, the cell counts of the cerebrospinal fluid was normal in all the three patients, the protein level was significantly increased, there were new symmetrical lesions on head magnetic resonance imaging in 3 patients.After symptomatic treatment and immunotherapy including early use of hormone, human gamma globulin and plasma exchange, all the patients were survived, but had different degrees of new dysfunction of the nervous system.Conclusion:Severe COVID-19 encephalopathy can occur in the acute phase of SARS-CoV-2 infection, mostly manifested as high fever, convulsions and severe disturbance of consciousness, combined with multiple organ dysfunction and irreversible nervous system damage.Early supportive treatment, brain protective treatment and immunotherapy are helpful to improve the prognosis of patients.

Retrospective study of "integrated prevention strategy" in preventing nipple and areola ischemia after single-port endoscopic subcutaneous mastectomy / 国际外科学杂志

Objective:To explore the preventive value of "integrated prevention strategy" for nipple and areola ischemia after single-port endoscopic subcutaneous mastectomy.Methods:The clinical data of 72 patients with breast cancer who received single-port endoscopic subcutaneous mastectomy in Beijing Friendship Hospital, Capital Medical University from July 2019 to July 2021 were retrospectively analyzed, they were all female. The follow-up period was up to July 2022. According to the perioperative treatment methods, the patients were divided into observation group ( n=40) and control group ( n=32). The patients in the observation group who adopted the "integrated prevention strategy" scheme, and patients in the control group who adopted the conventional treatment scheme. The incidence of postoperative nipple and areola ischemic was compared between the two groups, and the postoperative cosmetic effect, quality of life and satisfaction of patients were evaluated. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; the Chi-square test was used to compare the data groups. Results:The postoperative drainage volume in the observation group was significantly lower than that in the control group [(632.40±226.37) mL vs (774.91±239.85) mL], and the difference was statistically significant ( P=0.013). Two weeks after operation, there was 1 case of nipple and areola ischemia in the observation group, and 7 cases in the control group, the difference was statistically significant between the two groups ( P=0.019). Twelve months after operation, the score of breast satisfaction (83.93±11.64 vs 67.28±11.52), chest satisfaction (89.63±8.06 vs 83.03±9.49) and psychosocial well-being (89.43±12.42 vs 78.88±10.40) in the observation group were better than those in the control group, the differences were statistically significant ( P<0.05). Conclusion:"Integrated prevention strategy" can effectively prevent the occurrence of nipple and areola ischemic after single-port endoscopic subcutaneous mastectomy and improve patient satisfaction, which has certain promotion value.

Brain-computer interface coding method based on high-frequency dual-frequency SSVEP / 国际生物医学工程杂志

Objective:To improve the users’ comfort of steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) through high-frequency stimulation and overcome the problem of accuracy decline caused by high frequency by combining dual-frequency encoding.Methods:Two dual-frequency high-frequency 60-instruction paradigms based on left and right visual fields and checkerboard stimuli were designed based on the 25.5 - 39.6 Hz frequency. Thirteen subjects participated in the experiment, and spectrum and spatial characteristics analyses were performed on SSVEP signals. The filter bank parameters were optimized based on the spectrum characteristics. Extended canonical correlation analysis (eCCA), ensemble task-related component analysis (eTRCA), and task-discriminant component analysis (TDCA) were used for SSVEP recognition.Results:Stable SSVEP was successfully induced in both the left and right visual fields and the checkerboard grid paradigm. The left and right visual fields had high signal-to-noise ratios for the fundamental frequency and its harmonics and weak signal-to-noise ratios for intermodulation components, whereas the intermodulation components of the 2 stimulus frequencies of the checkerboard grid, f1 + f2, had significantly higher signal-to-noise ratios than the second harmonic components above 30 Hz, and there was also a f2 ? f1 component and a 2 f1 ? f2 component. Combined with brain topography, it can be seen that the f1 and f2 response components of the left and right visual fields are located on opposite sides of the visual field, while the checkerboard grids are both concentrated in the center of the occipital region. Regarding the lateralization of brain topography amplitude and signal-to-noise ratio, the mean values of the PO3 and PO4 signal-to-noise ratios at the stimulation frequency of the left and right visual fields are consistent with the contralateral response characteristics. The 5 fb ? 1 method is the optimal filter set setting method, and the recognition correctness rate of TDCA for the left and right visual fields is the highest. However, the comparison of the recognition correctness rate of tessellated lattice eTRCA and TDCA is not statistically significant ( P > 0.05). The information transmission rates of the three algorithms all increase and then decrease with the increase in data length. Conclusions:The designed dual-frequency, high-frequency SSVEP-BCI paradigm is able to better balance performance and comfort and provides a basis for practical large instruction set BCI design methods.

Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

Research progress on prevention and local intervention of oral mucositis in patients with hematopoietic stem cell transplantation / 中华口腔医学杂志

Oral mucositis (OM) is a common complication during hematopoietic stem cell transplantation. When OM occurs, with the destruction of oral mucosal barrier function, the formation of oral bacterial environment is accelerated, which has a negative impact on the life quality and clinical outcomes of patients. OM can be prevented by keeping the oral cavity clean, using the mouthwash properly, and limiting the delivery of cytotoxic drugs to oral tissues. This review describes the research progress on the prevention and local intervention of OM in patients with hematopoietic stem cell transplantation, in order to provide ideas for the selection of clinical intervention and management strategies on OM, and to provide references for exploring effective management methods for OM.

Application of Modified Intraoperative Axillary Fluoroscopy for Posterior Acromioclavicular Joint Dislocation / 中山大学学报(医学科学版)

ObjectiveThe study aims to determine whether the horizontal posterior displacement of the distal clavicle in patients with acromioclavicular joint dislocation can be corrected via the application of modified intraoperative axillary fluoroscopy. MethodsFrom February 2019 to April 2021， 50 patients with Rockwood type Ⅲ acromioclavicular joint dislocation eligible for inclusion were randomly divided into two groups： the normal （32 cases） and the experimental （18 cases）. The conventional anteroposterior position radiographs were obtained to detect the surgery effect on the patients in the normal group. In experimental group， modified intraoperative axillary radiographs were obtained， with the concept of polar coordinates introduced to reduce the horizontal posterior translation of the clavicle. Then we compared the perioperative parameters， such as average operative time， intraoperative blood loss between the two groups. The Constant score was used for assessing the postoperative function of the shoulder joint in the follow-up visits. ResultsNo statistically significant difference was found in gender， age， duration of injury， underlying diseases， intraoperative blood loss and operative time between the two groups. The postoperative shoulder function score of the experimental group was higher than that of the normal group. ConclusionsThe application of modified intraoperative axillary fluoroscopy is recommendable for accurately reducing posterior translation of the distal clavicle， and meanwhile helpful for the precise placement of the clavicular plate.

Co-load of silybin and doxorubicin by MoS2 nanosheets for synergetic chemotherapy and photothermal therapy of lung cancer / 药学学报

The active ingredient of traditional Chinese medicine, silybin (SBN), can inhibit the proliferation of cancer cells and enhance the anticancer effect of doxorubicin (DOX). However, due to non-targeting and short half-life of SBN and DOX, as well as different administration routes and pharmacokinetic processes, this combination drug cannot act on the tumor in the set order, seriously eliminating the synergistic effect between them and limiting the effect in vivo. Therefore, we intended to construct a nano-delivery system based on molybdenum disulfide (MoS2), modified by polyethylene glycol (PEG) and sialic acid (SA), and co-loaded with SBN and DOX. The system induced the release of combined drugs under the dual-stimulation of pH and near infra-red (NIR), increased the free concentration of intracellular drugs, so as to achieve the synergistic effect between them. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Fujian University of Traditional Chinese Medicine. MoS2-PEG-SA-SBN/DOX circulated in vivo, and effectively accumulated at tumor sites through enhanced permeability and retention effect (EPR) and SA-mediated active targeting. Under near infrared light irradiation, MoS2-PEG-SA-SBN/DOX realized the combination of synergistic chemotherapy and photothermal therapy for tumor, thus achieving excellent anti-tumor effect in vivo. This study can provide a new idea and strategy for the clinical treatment of lung cancer. Taken together, MoS2-PEG-SA-SBN/DOX can offer a new idea and strategy for the clinical treatment of lung cancer.

Effect of sodium fluoride on myocardial damage by regulating apoptosis through JNK signaling pathway / 环境与职业医学

Background It has been found that fluoride may cause cardiomyocyte damage. c-Jun N-terminal kinases (JNK) signaling pathway plays an important role in apoptosis, but its role in fluorosis-induced cardiomyocyte damage is still unknown yet. Objective To explore the toxic effect of sodium fluoride (NaF) on H9c2 cardiomyocytes of rats and whether NaF affects cardiomyocyte apoptosis through the JNK signaling pathway. Methods According to the concentrations of sodium fluoride and whether sp600125 (JNK inhibitor) was added, cardiomyocytes of rats were divided into six groups, including control group, SP600125 group (SP group), 0.24, 0.48, and 0.96 mmol·L−1 NaF groups, and 0.96 mmol·L−1 NaF+SP600125 group (NaF+SP group). Cardiomyocytes exposed to NaF for 24 h were observed using a fluorescence inverted microscope. The changes of cell viability at 24, 48, and 72 h after the treatment were detected by CCK-8 method. The levels of reactive oxygen species (ROS) at 24 h after the treatment in H9c2 cardiomyocytes were determined by fluorescent probe method. The expression levels of Bcl-2, Bax, Caspase-3, and JNK mRNA at 24 h after the treatment were detected by real-time PCR. The protein expression levels of Bcl-2, Bax, Caspase-3, and p-JNK at 24 h after the treatment were detected by Western blotting. Results Compared with the control group, after being exposed to 0.48 and 0.96 mmol·L−1 NaF for 24 h, the cell growth density decreased. With the increase of NaF concentration, rounded cells and some suspended dead cells appeared. At 24h after exposure to NaF, the cell viability of the 0.48 and 0.96 mmol·L−1 NaF groups decreased compared with the control group (P<0.05). At 48h and 72h after exposure to NaF, the cell viability levels of the NaF treated groups were significantly lower than that of the control group (P<0.05). After NaF exposure for 24 h, compared with the control group, the intracellular ROS levels were increased (P<0.05); the mRNA expression levels of Bcl-2 were decreased to varying degrees, especially in the 0.48 and 0.96 mmol·L−1 NaF groups (P<0.05); the mRNA expression levels of Bax, Caspase-3, and JNK were increased (P<0.05); the protein expression levels of Bcl-2 were reduced (P<0.05); the protein expression levels of Bax, Caspase-3, and p-JNK were elevated (P<0.05). Compared with the 0.96 mmol·L−1 NaF group, the cell viability of the NaF+SP group was increased, the intracellular ROS level was decreased, the mRNA expression levels of Bax, Caspase-3, and JNK were decreased, the protein expression level of Bcl-2 was increased, and the protein expression levels of Bax, Caspase-3, and p-JNK were decreased (P<0.05); the expression level of Bcl-2 mRNA had a rising trend but showed no statistical significance (P>0.05). Conclusion Cardiomyocyte damage after excessive fluoride exposure may result from fluoride inducing excessive ROS production in cardiomyocytes, which may activate the JNK signaling pathway and induce cardiomyocyte apoptosis.

The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan Plateau / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.

The Risk and Survival Analysis of Multiple Malignancies in Hematologic Malignancy Patients: A Single Chinese Center Retrospective Study, 2009 through 2017 / 中国实验血液学杂志

OBJECTIVE@#To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients.@*METHODS@#The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively.@*RESULTS@#A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival.@*CONCLUSION@#In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.

Effect of guarana on lipid metabolism in obese rats: a study based on lipidomics / 中国中药杂志

This study investigated the effect of guarana on plasma lipid metabolites in obese rats and analyzed its mechanism in the treatment of dyslipidemia in obesity. High-fat diet was used to establish obese rat models, and the therapeutic effect of guarana on obese rats was evaluated by measuring body weight, white fat, liver weight, and lipid content, as well as observing liver histomorphology. Lipid metabolites in plasma of rats in each group were detected by UHPLC-Q-TOF-MS lipidomics. The protein expressions of fatty acid synthase, acetyl-CoA carboxylase 1, triglyceride synthesis enzyme, carnitine palmitoyltransferase Ⅰ, and acetyl-coenzyme A acyltransferase 2 in rat liver were detected using Western blot. The results revealed that guarana significantly reduced body weight, white fat, and liver weight of obese rats due to high-fat diet, and alleviated dyslipidemia and liver steatosis. Lipidomics showed that some triglycerides and phospholipids were significantly elevated in the high-fat model group, and part of them was reduced after guarana treatment. Western blot found that guarana inhibited the expression of hepatic fatty acid and triglyceride synthesis-related proteins and increased the expression of fatty acid β-oxidation-related proteins. Abnormalities in triglyceride and phospholipid metabolism are the main characteristics of plasma lipid metabolism in obese rats induced by high-fat diet. Guarana may regulate partial triglyceride and phospholipid metabolism by inhibiting hepatic fatty acid and triglyceride synthesis and increasing fatty acid β-oxidation, thereby improving rat obesity and dyslipidemia.

Clonotypic analysis of immunoglobulin heavy chain sequences among 44 patients with Waldenström macroglobulinemia / 中华医学遗传学杂志

OBJECTIVE@#To analyze the correlation between the mutational status of immunoglobulin heavy chain variable (IGHV) gene with the prognosis of patients with Waldenström macroglobulinemia (WM).@*METHODS@#Immunoglobulin heavy chain gene (IGH) clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients. The usage characteristics of IGHV-IGHD-IGHJ gene was explored.@*RESULTS@#The most common IGHV subgroup was IGHV3, which was similar to the data from the Institute of Hematology of Chinese Academy of Medical Science. IGHV3-23 (20.45% vs. 15.44%) and IGHV3-74 (11.36% vs. 7.35%) were the main fragments used, which was followed by IGHV4 gene family (15.91% vs. 24.26%). However, no significant correlation was found between the IGHV4 usage and the prognosis of the patients. Should 98% be taken as the cut-off value for the IGHV mutation status, only 5 patients had no IGHV variant, and there was no correlation with the prognosis. Based on the X-tile analysis, 92.6% was re-selected as the cut-off value for the IGHV variant status in such patients. LDH was increased in 26 patients (59.1%) without IGHV variant (P < 0.05), whilst progression-free survival (P < 0.05) and overall survival (P < 0.05) were significantly shorter compared with those with IGHV variants.@*CONCLUSION@#The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of Chinese Academy of Medical Science, albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients. Furthermore, 98% may not be appropriate for distinguishing the IGHV variant status in WM patients.

Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism / 中国中药杂志

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Current status and outlook of medical treatment for KRAS-mutated non-small cell lung cancer / 中华肿瘤杂志

Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.

Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Discussion of the process of conducting an investigator-initiated research / 中国胸心血管外科临床杂志

@#The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.