Optimization of non-bioartificial liver technology and research advances in biological artificial liver / 临床肝胆病杂志

Liver failure is a common clinical syndrome with rapid progression and poor prognosis. Currently， there are still limited internal medical treatment methods for liver failure， and artificial liver support therapy is an effective treatment method. Non-bioartificial liver technology is widely used in clinical practice， and clinicians should determine the starting time， mode， and specific parameters of treatment according to the pathophysiological mechanism and dynamic evolution process of the disease， as well as the specific conditions of patients. Compared with non-bioartificial liver， biological artificial liver can better simulate the biological function of liver cells. At present， substantial progress has been made in its core technology， and related clinical studies are being conducted actively， suggesting a vast potential for future development. This article summarizes and discusses the optimization of non-bioartificial liver technology and the advances in biological artificial liver， in order to provide a reference for the clinical application and research of artificial liver technology.

Role of NLRP3 Inflammasome in IgA Nephropathy and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

IgA nephropathy is recognized as the most common primary glomerular disease， with up to 20%-40% of patients developing end-stage kidney disease within 20 years of onset. The deposition of IgA1-containing immune complexes targeting glycosylation defects in the mesangial region and the subsequent inflammation caused by T lymphocyte activation are considered as the main causes of IgA nephropathy， and innate immunity is also involved in the pathogenesis. Nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） is a newly discovered pattern recognition receptor expressed in renal intrinsic cells such as renal tubular epithelial cells， mesangial cells， and podocytes. Activated by external stimuli， NLRP3 can form NLRP3 inflammasomes with apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC）. The NLRP3 inflammasome can activate cysteine aspartate-specific protease-1 （Caspase-1）， causing the maturation and release of interleukin-18 （IL-18） and interleukin-1β （IL-1β） involved in inflammation. Increasing evidence has suggested that NLRP3 inflammasomes are involved in the pathogenesis and progression of IgA nephropathy and associated with the damage of renal intrinsic cells such as podocytes， mesangial cells， endothelial cells， and renal tubular epithelial cells. Chinese medicine can regulate inflammatory cytokines and their signaling pathways by acting on NLRP3 inflammasomes and related molecules， exerting therapeutic effects on IgA nephropathy. This article introduces the role of NLRP3 inflammasomes in IgA nephropathy and reviews the clinical and experimental research progress of Chinese medicine intervention in IgA nephropathy via NLRP3 inflammasomes， aiming to provide a reference for further research and application of Chinese medicine intervention in the NLRP3 inflammasome as a new therapeutic target.

TCM Treatment of Podocyte Injury in IgA Nephropathy Based on Multiple TCM Theories： A Review / 中国实验方剂学杂志

IgA nephropathy is the most common primary glomerular disease in China. Its clinical manifestations are mainly proteinuria， hematuria， hypertension， edema， hyperuricemia， etc. Most patients have hidden onset. 30%-40% of patients develop into end stage renal disease 10-20 years after diagnosis and rely on dialysis or kidney transplantation to maintain their lives， which is extremely harmful. Proteinuria is a common clinical manifestation of this disease， and most patients have small-to-moderate amounts of proteinuria， while 10%-24% of patients have large amounts of proteinuria. Proteinuria is the main risk factor affecting the progression of renal function in IgA nephropathy. Podocytes are the terminal part of the glomerular filtration barrier， and various factors can affect the fusion and detachment of podocyte processes that occur after podocyte injury. They are common histological lesions in IgA nephropathy and are key factors leading to proteinuria and the continuous progression of the disease. At present， Western medicine lacks targeted treatment for podocyte injury， with limited intervention methods. Drugs such as glucocorticoids are often used for treatment， and there are many adverse reactions. Based on the physiological function of podocytes， pathological and physiological changes after injury， and histological morphology of this disease， it is believed that it is closely related to traditional Chinese medicine's "Xuanfu Theory" "Kidney Collateral Syndrome" "Collateral Disease Theory"， and "Dry Blood Theory". More and more studies have shown that traditional Chinese medicine， which has the characteristics of multiple links， pathways， and targets， has a significant therapeutic effect on podocyte injury in IgA nephropathy. It can protect podocytes and reduce proteinuria and has good application and research prospects. This article systematically summarizes the mechanism and morphological changes of podocyte injury in IgA nephropathy， the understanding of podocyte injury in traditional Chinese medicine theory， and the research progress in traditional Chinese medicine treatment of podocyte injury in IgA nephropathy， so as to provide a reference for further research and application of traditional Chinese medicine intervention in podocyte injury in IgA nephropathy.

Application of tissue culture technology of medicinal plants in sustainable development of Chinese medicinal resources / 中国中药杂志

Chinese medicinal resources are the cornerstone of the sustainable development of traditional Chinese medicine industry. However, due to the fecundity of species, over-exploitation, and limitations of artificial cultivation, some medicinal plants are depleted and even endangered. Tissue culture, a breakthrough technology in the breeding of traditional Chinese medicinal materials, is not limited by time and space, and can allow the production on an annual basis, which plays an important role in the protection of Chinese medicinal resources. The present study reviewed the applications of tissue culture of medicinal plants in the field of Chinese medicinal resources, including rapid propagation of medicinal plant seedlings, breeding of novel high-yield and high-quality cultivars, construction of a genetic transformation system, and production of secondary metabolites. Meanwhile, the current challenges and suggestions for the future development of this field were also proposed.

Role of brown adipose tissue in phlegm-dampness metabolic syndrome based on infrared thermal imaging / 中国中药杂志

This study aimed to explore the infrared manifestation and role of brown adipose tissue(BAT) in phlegm-dampness me-tabolic syndrome(MS), and to provide objective basis for clinical diagnosis and treatment of phlegm-dampness MS. Subjects were selected from the department of endocrinology and ward in the South District of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from August 2021 to April 2022, including 20 in healthy control group, 40 in non phlegm-dampness MS group and 40 in phlegm-dampness MS group. General information, height and weight of the subjects were collected and body mass index(BMI) was calculated. Waist circumference(WC), systolic blood pressure(SBP) and diastolic blood pressure(DBP) was measured. Triglyceride(TG), high density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), leptin(LP), adiponectin(ADP) and fibroblast growth factor-21(FGF-21) were detected. The infrared thermal image of the supraclavicular region(SCR) of the subjects before and after cold stimulation test was collected by infrared thermal imager and the changes of infrared thermal image in the three groups were observed. In addition, the differences in the average body surface temperature of SCR among the three groups were compared, and the changes of BAT in SCR were analyzed. The results showed compared with the conditions in healthy control group, the levels of WC, SBP, DBP, TG and FPG in MS groups were increased(P<0.01), and the HDL-C level was decreased(P<0.01). Compared with non phlegm-dampness MS group, phlegm-dampness MS group had higher conversion score of phlegm dampness physique(P<0.01). According to the infrared heat map, there was no difference in the average body surface temperature of SCR among the three groups before cold stimulation. while after cold stimulation, the average body surface temperature of SCR in MS groups was lower than that in healthy control group(P<0.05). After cold stimulation, the maximum temperature of SCR and its arrival time in the three groups were as follows: healthy control group(3 min)>non phlegm-dampness MS group(4 min)>phlegm-dampness MS group(5 min). The thermal deviation of SCR was increased and the average body surface temperature of left and right sides were higher(P<0.01) in healthy control group and non phlegm-dampness MS group, while the thermal deviation of SCR did not change significantly in the phlegm-dampness MS group. Compared with that in healthy control group, the elevated temperature between left and right sides was lower(P<0.01, P<0.05), and compared with that in non phlegm-dampness MS group, the elevated temperature of left side was lower(P<0.05). The changes of the average body surface temperature of SCR in the three groups were in the order of healthy control group>non phlegm-dampness MS group>phlegm-dampness MS group. Compared with the conditions in healthy control group and non phlegm-dampness MS group, FINS, BMI and FGF-21 levels were increased(P<0.01,P<0.05), while ADP level was decreased(P<0.01, P<0.05) in phlegm-dampness MS group. Moreover, the LP level in phlegm-dampness MS group was higher than that in non phlegm-dampness MS group(P<0.01). It was observed in clinical trials that after cold stimulation, the average body surface temperature of SCR in MS patients was lower than that of the healthy people; the thermal deviation of SCR did not change significantly in the phlegm-dampness MS patients, and the difference in their elevated temperature was lower than that in the other two groups. These characteristics provided objective basis for clinical diagnosis and treatment of phlegm-dampness MS. With abnormal BAT related indicators, it was inferred that the content or activity of BAT in SCR of phlegm-dampness MS patients were reduced. There was a high correlation between BAT and phlegm-dampness MS, and thus BAT might become an important potential target for the intervention in phlegm-dampness MS.

Construction of Artificial Cells with Application to Investigate Peritoneal Metastasis in Ovarian Cancer / 中山大学学报(医学科学版)

ObjectiveTo construct a human ovarian cancer cell line SKOV3 （SK-Luc-EGFP） stably co-expressing luciferase （Luc） and enhanced green fluorescent protein （EGFP） and to explore its application in ovarian cancer research both in vitro and in vivo. MethodsThe recombinant plasmid pCDH-Luc-T2A-EGFP-Puro was constructed by introducing a Luc-T2A-EGFP fusion gene fragment amplified by Overlap PCR into plasmid vector. The three-plasmid lentivirus packaging system was transfected into HEK 293T cells and the viral supernatant was harvested to infect SKOV3 cells. SK-Luc-EGFP cell line with the highest fluorescence intensity of EGFP was obtained by puromycin selection and flow cytometry assessment， and the Luc expression of the cell line was subsequently validated by in vitro bioluminescent assay. SK-Luc-EGFP cells were further explored for the following applications： distinguishing SK-Luc-EGFP cells from non-tumor cells in ascites by flow cytometry and confocal microscopy； visualizing adhesion of SK-Luc-EGFP cells to mesothelial cells or omentum by fluorescence microscopy； monitoring process of SK-Luc-EGFP tumorigenesis by in vivo bioluminescence imaging. ResultsA recombinant lentiviral expression plasmid pCDH-Luc-T2A-EGFP-Puro was constructed and packaged into lentiviral particles that were then transfected into SKOV3 cells to generate SK-Luc-EGFP cell line. The purity of SK-Luc-EGFP cells based on EGFP expression was 100% as validated by fluorescence microscopy and flow cytometry； SK-Luc-EGFP cells could be visually distinguished from non-tumor cells in ascitic fluid by flow cytometry and confocal imaging. Moreover， Luc expression in SK-Luc-EGFP cells was verified by in vitro bioluminescence assay， and a linear relationship with a correlation coefficient of 0.997 9 was found between cell number and the bioluminescent signal. Adhesion of SK-Luc-EGFP cells to mesothelial cells was directly observed by fluorescence imaging in in vitro adhesion assay； peritoneal adhesion of SK-Luc-EGFP cells to omentum was also observed after intraperitoneal （i.p.） injection of SK-Luc-EGFP cells in nude mice； in the peritoneal metastasis mouse model established by i.p. injection of SK-Luc-EGFP cells， monitoring of tumorigenesis process was achieved by in vivo bioluminescence imaging. ConclusionSK-Luc-EGFP cell line is a useful tool for investigating ovarian cancer in vitro and in vivo.

Short-term Outcomes and Long-term Survival Outcomes of Elderly Patients (Over 80 Years of Age) with Colorectal Cancer Who Received Laparoscopic Versus Open Surgery / 肿瘤防治研究

Objective To examine short-term outcomes and long-term survival of elderly patients (aged over 80 years) with colorectal cancer who received laparoscopic versus open surgery. Methods A total of 313 patients over 80 years old with colorectal cancer who underwent radical surgery were included.According to the surgical method, all patients were divided into open-surgery group (n=143) and laparoscopic surgery group (n=170).Baseline data were balanced between the two groups by using propensity score matching.Kaplan-Meier was used to draw the survival curve, and survival was compared by Log rank tests.Cox proportional risk model was used to analyze the effects of all factors on overall survival (OS) and disease-free survival (DFS). Results After matching, 93 patients were included in each group.The mean intraoperative blood loss, the incidence of overall postoperative complications and gradeⅠ-Ⅱ complications in the laparoscopic surgery group were significantly lower than those in the open surgery group (all P < 0.05).The time to first flatus, the time to oral feeding, and postoperative hospital stays in the laparoscopic surgery group were significantly shorter than those in the open surgery group (all P < 0.05).The mean number of lymph-node dissection was also significantly higher in the laparoscopic surgery group than in the open surgery group (P=0.030).Patients in both groups had similar 5-year OS (P=0.594) and DFS (P=0.295).Multivariate Cox prognostic analysis showed that CEA level > 5 ng/ml, pathological TNM stage Ⅲ, and perineural invasion were independent risk factors for poor OS and DFS. Conclusion Compared with open surgery, laparoscopic surgery can provide better short-term advantages and similar long-term outcomes for colorectal cancer patients over 80 years of age.

Study on changes of proliferation, migration and invasion abilities of radiation-induced polyploid colon cancer SW1116 cells and their progeny and the related mechanisms / 肿瘤研究与临床

Objective:To investigate the characteristics related to proliferation, migration and invasion of radiation-induced polyploid colon cancer SW1116 cells and their progeny.Methods:Colon cancer SW1116 cells were conventionally cultured in Leibovitz's L-15 medium containing 10% fetal bovine serum. SW1116 cells at logarithmic growth stage were irradiated with 7 Gy X-ray, and the morphological changes of the cells were observed by inverted microscope on days 3, 5, 10 and 19 after radiation induction. According to the morphological changes of the cells, the cells at day 3 after radiation induction were labeled as polyploid giant cancer cell (PGCC) group, and the cells at day 19 were recorded as PGCC progeny group. SW1116 cells without radiation induction were used as control group. Flow cytometry was used to detect cell ploidy in the control, PGCC and PGCC progeny groups, CCK-8 assay was used to detect the proliferation ability of the three groups, cell migration and invasion abilities of the three groups were detected by cell scratch assay and Transwell assay, and Western blotting was used to detect the expressions of cell cycle and proliferation-related proteins and epithelial-mesenchymal transition (EMT) marker N-cadherin (N-cad) in the three groups.Results:The volume of SW1116 cells gradually became larger on days 3, 5 and 10 after radiation induction, and returned to normal on day 19. The proportions of polyploid (DNA content >4N) cell subsets in the control group, PGCC group and PGCC progeny group were (2.3±1.1)%, (23.1±8.1)% and (3.2±0.5)%, the difference was statistically significant ( F = 18.52, P < 0.05), and the proportion of polyploid cell subpopulations in the PGCC group was higher than that in the control group ( t = 5.38, P < 0.01), but the differences between the PGCC progeny group and the control group were not statistically significant ( t = 0.22, P > 0.05). After 72 h of culture, the cell proliferation rates of the control, PGCC and PGCC progeny groups were (100.0±4.1)%, (73.5±0.7)% and (123.9±3.5)%, and the difference was statistically significant ( F = 190.27, P < 0.001). After 48 h of cell scratching, the scratch healing rates in the control, PGCC and PGCC progeny groups were (38.0±2.7)%, (41.5±4.0)% and (63.7±4.2)%, and the difference was statistically significant ( F = 43.05, P < 0.001). After 24 h of culture, the number of invasive cells in the control, PGCC and PGCC progeny groups was 12.9±1.2, 3.4±0.6 and 23.7±1.5, and the difference was statistically significant ( F = 63.64, P < 0.001). The expression levels of cell cycle-related proteins P-cdc25c, cdc25c and cdc2 in the PGCC group were lower than those in the control group (all P < 0.05), and the expression levels of transcription factor-related proteins E2F-2, E2F-3 and EMT marker N-cad were downregulated compared with the control group (all P < 0.05); the expression levels of P-cdc25c, cdc25c, cdc2, E2F-2, E2F-3 and N-cad proteins in the PGCC progeny group were higher than those in the control group (all P < 0.05). Conclusions:Radiation can induce colon cancer SW1116 cells to produce polyploid, which may then generate daughter cells through asymmetric mitosis and gain new life, and then promote the recurrence and metastasis of colon cancer.

The effects of transcranial magnetic stimulation on the expression of P2X7R and GFAP in the prefrontal cortex and hippocampus of mice modeling chronic depression / 中华物理医学与康复杂志

Objective:To investigate any effect of repeated transcranial magnetic stimulation (rTMS) on the expression of P2X7 receptor (P2X7R) and glial fibrillary acid protein (GFAP) in the prefrontal cortex and hippocampus of mice modeling depression.Methods:Thirty C57BL/6 mice were divided into a control group ( n=10) and a depression group ( n=20). The mice of the control group were raised in group (five mice per cage), while those of the depression group were kept alone for six weeks to induce depression. Among them, 16 were successfully modeled and randomly divided into a model group ( n=8) and an rTMS group ( n=8). The rTMS group received five sessions per week of 10Hz rTMS for 4 weeks. Any changes in depression-like behavior were observed and the expression of P2X7R and GFAP in the prefrontal cortex and hippocampus was measured. Results:Compared to the control group, a significant decrease was observed in the sucrose consumption rate in the sucrose preference test, in the distance moved in the open field test and in the expression of GFAP protein. But there was a significant increase in the immobile time in the tail suspension test and in the expression of P2X7R protein in the prefrontal cortex and hippocampus in the model group. At the conclusion of the experiment the differences in the sucrose consumption rate, the distance moved, GFAP protein expression, immobile time and P2X7R protein expression between the rTMS and the model group were all statistically significant.Conclusion:rTMS can reduce depression-like behavior, at least in mice. That may be related to inhibiting P2X7R expression and promoting GFAP expression in the prefrontal cortex and hippocampus.

Surveys on management of neonatal respiratory distress syndrome in ten hospitals in Northwest China in 2016 and 2021 / 中华围产医学杂志

Objective:To analyze the status of neonatal respiratory distress syndrome (RDS) management in 10 hospitals in Northwest China over the past five years and to investigate the strategies for improving the prevention and treatment of RDS.Methods:This retrospective study involved premature infants with RDS who were admitted to the neonatal intensive care units (NICU) of 10 hospitals (six in Shaanxi Province, three in Gansu Province, and one in Xinjiang Uygur Autonomous Region) of the Northwest China Neonatal Collaborative Group within 3 d after birth from January 1 to December 31, 2016, and from January 1 to December 31, 2021. Basic information, perinatal condition, treatment approaches, complications, and prognosis of the patients were compared. T-test, rank sum, and Chi-square tests were used for statistical analysis. Result:(1) This study enrolled 322 premature infants with RDS in 2016 and 349 in 2021. Premature infants at the gestational age of 30 to 33 weeks were mainly affected, and the majority were male [64.3% (207/322) and 57.3% (200/349)]. The average maternal age in 2021 was older than that in 2016 [(30.6±4.8) years vs (28.6±5.4) years, t=24.02, P<0.001], and the proportion of women at advanced maternal age was also higher in 2021 [19.2% (67/349) vs 12.4% (40/322), χ2=4.18, P<0.05]. (2) The proportions of pregnancies conceived with assisted reproductive technologies [11.7% (41/349) vs 1.9% (6/322), χ2=25.12], underwent routine prenatal examinations [58.5% (204/349) vs 30.4% (98/322), χ2=53.33], exposed to steroids [62.2% (217/349) vs 28.6% (92/322), χ2=82.58] and delivered by cesarean section or elective cesarean section [73.6% (257/349) vs 51.6% (166/322), χ2=35.06; 24.1% (84/349) vs 6.5% (21/322), χ2=39.07], as well as the ratio of cesarean scar pregnancy [7.4% (26/349) vs 3.4% (11/322), χ2=5.23] were all higher in 2021 than those in 2016 (all P<0.05). Moreover, the incidence of fetal distress [30.1% (105/349) vs 20.2% (65/322), χ2=8.68], gestational hypertension [24.6% (86/349) vs 13.0% (42/322), χ2=14.59], premature rupture of membranes [16.0% (56/349) vs 10.2% (33/322), χ2=4.89], meconium-stained amniotic fluid [12.6% (44/349) vs 5.6% (18/322), χ2=9.83], placental abruption [10.3% (36/349) vs 5.3% (17/322), χ2=5.84], gestational diabetes mellitus [10.3% (36/349) vs 1.6%(5/322), χ2=22.41], chorioamnionitis [4.6%(16/349) vs 0.9% (3/322), χ2=8.12], thyroid dysfunction [4.3% (15/349) vs 0.6% (2/322), χ2=7.88] and heart disease [4.3% (15/349) vs 0.3% (1/322), χ2=9.17] were higher in 2021 than in 2016 (all P<0.05). (3) In 2021, the rate of pulmonary surfactant (PS) usage, the dosage of porcine PS, and the proportion of bovine PS usage were all significantly higher than those in 2016 [73.6% (257/349) vs 67.1% (216/322), χ2=11.62; (178.5±38.0) mg/kg vs (165.2±42.8) mg/kg, t=7.85; 47.9% (123/257) vs 19.4% (42/216), χ2=41.72; all P<0.01]. No significant difference in the incidence of intubation-surfactant-extubation (INSURE), early PS administration (≤2 h after birth), or the arterial blood gas values before and after PS treatment was found between the cases enrolled in 2021 and 2016. The duration of antibiotic treatment [7.0 d (5.0-14.0 d) vs 5.0 d (1.0-8.0 d), Z=7.55] and assisted ventilation [144 h (81-264 h) vs 73 h (47-134 h), Z=8.20] and the median hospital stay [24 d(14-42 d) vs 16 d (10-25 d), Z=6.74] were significantly longer in 2021 than in 2016 (all P<0.01). More patients required nasal intermittent positive pressure ventilation [29.6% (100/338) vs 1.0% (3/306), χ2=97.81] and conventional ventilation [42.6% (144/338) vs 30.1% (92/306), χ2=10.87] in 2021 as compared with those five years ago (both P<0.01). (4) In 2021, the incidence of patent ductus arteriosus [15.5% (54/349) vs 6.2% (20/322), χ2=63.40], bronchopulmonary dysplasia [9.2% (32/349) vs 2.8% (9/322), χ2=12.88], persistent pulmonary hypertension [5.4% (19/349) vs 0.6% (2/322), χ2=12.85], periventricular leukomalacia [4.3% (15/349) vs 1.2% (4/322), χ2=7.52] and pneumothorax [3.4% (12/349) vs 0.3% (1/322), χ2=9.68] increased as compared with those in 2016 (all P<0.05), while the incidence of nosocomial infection decreased significantly [7.4% (26/349) vs 19.6% (63/322), χ2=21.37, P<0.001]. (5) The cure rate of premature infants with RDS was 70.8% (247/349) in 2021, which was significantly higher than that in 2016 [56.2% (181/322), χ2=15.37, P<0.001]. Moreover, the rate of withdrawing treatment and the total mortality rate was lower in 2021 than in 2016 [7.7% (27/349) vs 14.3% (46/322), χ2=7.41; in-hospital: 1.4% (5/349) vs 5.6% (18/322), χ2=8.74; out of hospital: 8.3% (29/349) vs 13.7% (44/322), χ2=4.96; all P<0.05]. Conclusions:The clinical management of RDS in premature infants in the involved hospitals has been improved. However, there is room for improvement in prenatal examinations.

Effect of low-dose esketamine on remifentanil-induced postoperative hyperalgesia / 中华麻醉学杂志

Objective:To evaluate the effects of low-dose esketamine on remifentanil-induced postoperative hyperalgesia in the patients.Methods:Ninety-six American Society of Anesthesiologist Physical Status classificationⅠ or Ⅱ patients, aged 18-60 yr, with body mass index of 18-30 kg/m 2, scheduled for elective thyroidectomy under general anesthesia, were divided into 3 groups ( n=32 each) using a random number table method: control group (group C), esketamine administered before anesthesia induction group (group K1), and esketamine administered immediately after the end of surgery group (group K2). Esketamine 0.4 mg/kg was intravenously injected in group K1, and the equal volume of normal saline was given instead in C and K2 groups at 5 min before anesthesia induction. Anesthesia was induced by intravenous injection of propofol, remifentanil and rocuronium. Remifentanil was intravenously infused at a rate of 0.3 μg · kg -1·min -1 and 1.5%-2.5% sevoflurane was inhaled for anesthesia maintenance. Esketamine 0.4 mg/kg was intravenously injected in group K2 and the equal volume of normal saline was given instead in C and K1 groups immediately after the end of surgery. The mechanical pain thresholds of surgical incision and forearm of non-dominant hand were measured at 1 day before surgery and 30 min, 6 h, 24 h and 48 h after surgery, and flurbiprofen axetil was intravenously injected for rescue analgesia when the NRS score≥4 or the patient needed sedation. The intensity of pain was estimated using numeric rating scale at 30 min, 6 h, 24 h and 48 h after surgery. The intraoperative consumption of remifentanil, use of vasoactive drugs, recovery time, tracheal extubation time, duration of PACU stay, postoperative rescue analgesia and adverse reactions were recorded. Results:Compared with C group, the mechanical pain threshold around surgical incision and of the forearm of non-dominant hand was significantly increased at 30 min and 6 h after surgery in K1 and K2 groups ( P<0.05). Compared with C and K1 groups, the emergence time, tracheal extubation time, and duration of PACU stay were significantly prolonged, and the incidence of hallucinations and increased glandular secretion was increased in group K2 ( P<0.05). There were no significant differences in the consumption of remifentanil, intraoperative utilization rate of atropine and ephedrine, numeric rating scale scores at each time point after surgery, incidence of postoperative nausea and vomiting, and rate of rescue analgesia among the three groups ( P>0.05). Conclusions:Intravenous injection of small dose of esketamine (0.4 mg/kg) before anesthesia induction and immediately after the end of surgery can reduce postoperative hyperalgesia induced by remifentanil, and administration before anesthesia induction provides better efficacy in the patients.

Rapid authentication of different herbal medicines by heating online extraction electrospray ionization mass spectrometry / 药物分析学报

The rapid and accurate authentication of traditional Chinese medicines(TCMs)has always been a key scientific and technical problem in the field of pharmaceutical analysis.Herein,a novel heating online extraction electrospray ionization mass spectrometry(H-oEESI-MS)was developed for the rapid and direct analysis of extremely complex substances without the requirement for any sample pretreatment or pre-separation steps.The overall molecular profile and fragment structure features of various herbal medicines could be completely captured within 10-15 s,with minimal sample(＜0.5 mg)and solvent consumption(＜20 μL for one sample).Furthermore,a rapid differentiation and authentication strategy for TCMs based on H-oEESI-MS was proposed,including metabolic profile characterization,characteristic marker screening and identification,and multivariate statistical analysis model validation.In an analysis of 52 batches of seven types of Aconitum medicinal materials,20 and 21 key compounds were screened out as the characteristic markers of raw and processed Aconitum herbal medicines,respectively,and the possible structures of all the characteristic markers were comprehensively identified based on Com-pound Discoverer databases.Finally,multivariate statistical analysis showed that all the different types of herbal medicines were well differentiated and identified(R2X＞0.87,R2Y＞0.91,and Q2＞0.72),which further verified the feasibility and reliability of this comprehensive strategy for the rapid authentication of different TCMs based on H-oEESI-MS.In summary,this rapid authentication strategy realized the ultra-high-throughput,low-cost,and standardized detection of various complex TCMs for the first time,thereby demonstrating wide applicability and value for the development of quality standards for TCMs.

Clinical risk factors analysis of large volume central lymph node metastasis in papillary thyroid carcinoma / 中华内分泌外科杂志

Objective:To investigate the clinical risk factors of large volume lymph node metastasis (LV-LNM) in the central region of papillary thyroid cancer (PTC) .Methods:The clinical data of 1367 PTC patients admitted to the Department of Oncological Surgery, Hangzhou First People’s Hospital, Affiliated to Zhejiang University School of Medicine from Jan. 2016 to Jan. 2019 were retrospectively analyzed. There were 310 males and 1057 females. A total of 1644 cases of central region were included in the study.According to the number of lymph node metastasis in the central area, they were classified into small-volume lymph node metastasis (SV-LNM) group and LV-LNM group.71 cases of LV-LNM, 1573 cases of SV-LNM.The correlation between CLNM and LV-LNM and various clinicopathological features such as the sex, age, tumor size and so on of PTC patients was analyzed by chi-square test and Logistic regression analysis.Results:The proportion of CLNM in the affected side was 35.28% (580/1 644) , and the incidence of LV-LNM in the central area of the affected side was 4.32% (71/1644) . Univariate analysis showed that the LV-LNM in the central region of the affected side was closely correlated with gender, age, bilateral lesions, multiple lesions, size of lesions, membranous invasion and lateral cervical lymph node metastasis on the affected side were closely related ( P<0.05) . Multivariate regression analysis showed that male (OR=2.115, P=0.006) , age < 38 years old (OR=0.586, P=0.004) , multiple lesions on the affected side (OR=2.837, P=0.004) , lesions >7mm on the affected side (OR=1.762, P=0.002) and cervical lymph node metastasis on the affected side (OR=7.023, P<0.001) were independent predictors of LV-LNM in the central region of the affected side ( P<0.001) . The receiver operating characteristic curve (ROC) , sensitivity and specificity of LV-LNM predicted by the model were 0.839, 81.69% and 78.39%. The incidence of ipsilateral cervical lymph node metastasis in the affected central region of LV-LNM was 11.57 times higher than that of SV-LNM. Conclusion:PTC with male, age < 38 years old, multiple lesions on the affected side, lesion >7 mm and lateral cervical lymph node metastasis are prone to LV-LNM in the affected central region.

Efficacy and safety analysis of the zanubrutinib-based bridging regimen in chimeric antigen receptor T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Wendantang Treats Inflammation in Obesity （Syndrome of Phlegm-dampness） by Regulating PI3K/Akt/mTOR Pathway-mediated Adipocyte Autophagy / 中国实验方剂学杂志

ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines， autophagy markers， and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the adipocytes of the rat model of obesity （syndrome of phlegm-dampness） and to explore the material basis of inflammation in obesity （syndrome of phlegm-dampness） and the underlying mechanism of Wendantang intervention. MethodA total of 126 SD rats were randomized into 2 groups： 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity （syndrome of phlegm-dampness） for 8 weeks. After successful modeling， 48 obese rats were selected according to their body mass and randomized into a model control group， an orlistat （ORLI， 32.40 mg·kg-1） group， a rapamycin （RAPA， 2 mg·kg-1） group， and low-， medium-， and high-dose （4.45， 8.90， 17.80 g·kg-1， respectively） Wendantang groups， with 8 rats in each group. In addition， 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass， Lee's index， body fat ratio， and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 （ULK1）， Beclin1， human autophagy-related protein 5 （Atg5）， p62， and microtubule-associated protein 1 light chain 3 （LC3） Ⅰ/Ⅱ （markers of autophagy in adipocytes） was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， IL-4， IL-10， IL-13， and transforming growth factor （TGF）-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K， phosphatidylinositol triphosphate （PIP3）， Akt， mTORC1， ULK1， TSC1， and TSC2 in adipocytes. ResultCompared with the blank group， the modeling group showed increased body mass and Lee's index （P<0.01）， the obesity rate >20%， and phlegm-dampness syndrome manifestations such as physical obesity， decreased mobility， decreased appetite， lusterless and tight fur， loose stools， decreased responsiveness to the outside world， and decreased water intake. Compared with the normal control group， the model control group showed increased body mass， Lee's index， body fat ratio， adipocyte autophagy marker expression， pro- and anti-inflammatory cytokine levels （P<0.05， P<0.01）， down-regulated protein levels of classⅠ-PI3K， PIP3， Akt， mTORC1， TSC1， and TSC2 （P<0.01）， and up-regulated protein level of ULK1 （P<0.01）. The intervention groups showed lower body mass， body fat ratio， adipocyte autophagy marker protein expression， and protein levels of TNF-α， IL-6， IL-1β， MCP-1， IL-4， and IL-13 than the model control group （P<0.05， P<0.01）. Moreover， the RAPA and Wendantang （medium and high dose） groups showed lowered levels of IL-10 and TGF-β （P<0.01）， and the ORLI group showed down-regulated expression of TGF-β （P<0.01）. The expression of key molecules of the signaling pathway was up-regulated （P<0.05， P<0.01） while that of ULK1 was down-regulated （P<0.01） in all the intervention groups. Compared with the RAPA group， the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes （P<0.01）. In addition， the low-dose Wendantang group showed elevated levels of inflammatory cytokines （except TNF-α） （P<0.05， P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.05， P<0.01）. The levels of inflammatory cytokines （except IL-16， MCP-1， and IL-10） were elevated in the medium-dose Wendantang group （P<0.05， P<0.01）. The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups （P<0.05， P<0.01）. Compared with the ORLI group， low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes （P<0.01）， and the low-dose group showed elevated levels of inflammatory cytokines （IL-6， IL-4， and TGF-β） （P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.01）. The medium-dose Wendantang group showed up-regulated expression of IL-4 （P<0.01） and down-regulated expression of key molecules except PI3K of the signaling pathway （P<0.05， P<0.01）. The high-dose Wendantang group showed increased body mass， up-regulated expression levels of autophagy markers （ULK1， LC3 Ⅰ/Ⅱ） （P<0.05， P<0.01）， down-regulated expression of PIP3， mTORC1， and TSC1 （P<0.05， P<0.01）， and lowered levels of Beclin1， Atg5， TNF-α， and IL-13 （P<0.05， P<0.01）. ConclusionThe inflammation in obesity （syndrome of phlegm-dampness） is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.

Verbal and nonverbal cognitive function of aphasia after stroke based on Web of Science database: a visualized analysis / 中国康复理论与实践

ObjectiveTo visualize the research trends of verbal and nonverbal cognitive functions in patients with post-stroke aphasia (PSA). MethodsPapers about verbal and nonverbal cognitive functions after stroke were extracted from Web of Science Core Collection from establishment to August, 2022, and a bibliometric analysis was conducted on the distribution of articles published by year, author, journal, institution, and country. Author cooperation, author co-citation, journal co-citation, country/institution cooperation, dynamic evolution, keyword hotspots, and trends were visually analyzed by using VOSviewer software. ResultsA total of 1 630 publications were identified for final analysis. The first article related to the topic was retrieved in 2004. After that, the number of published papers showed an increasing trend year by year, with some fluctuations after 2019. Matthew A. Lambon Ralph and Elizabeth Jefferies were the authors who produced the most, were cited the most, and were the most influential. Neuropsychologia was a highly productive and well-cited publication. The University of Manchester in the United Kingdom and Johns Hopkins University in the United States were the nations/institutions with high yield and high centrality. Although China had a high yield and was in the top five, the centrality was insufficient. The dynamic emergence of keywords revealed that the research had gone through the following stages: evaluating the mechanism of language and nonverbal cognitive function impairment based on neuroimage, exploring the role of nonverbal cognitive dysfunction in pathology and recovery mechanisms of patients with PSA, examining the therapeutic mechanism of non-invasive brain stimulation and electronic tele-rehabilitation equipment, and revealing not only the frontal and temporal areas but also brain network supporting nonverbal cognition. ConclusionIn recent years, some achievements have been made in the researches on verbal and nonverbal cognitive function, particularly in the studies of the neuroimaging-based mechanisms of common damage and the intervention effects of synergistic therapy. In the future, academic cooperation between different regions and different teams needs to be strengthened. Further exploration should be focused on refining the cognitive neuropsychology and exploring new technologies to improve the therapeutic effect of PSA.

Meta-analysis of the effects of xenogeneic acellular dermal matrix dressings in the treatment of wounds in burn patients / 中华烧伤杂志

Objective: To evaluate the efficacy and safety of xenogeneic acellular dermal matrix (ADM) dressings for the treatment of wounds in burn patients. Methods: The meta-analysis method was adopted. Databases including Chinese Journal Full-text Database, Wanfang Database, VIP Database, and Chinese Biomedical Database were retrieved with the search terms in Chinese version of ", , , " and PubMed, Embase, Web of Science, and Cochrane Library were retrieved with the search terms in English version of "xenogeneic acellular dermal matrix, dressing, burn wound, burn" to obtain the publicly published randomized controlled trials on the efficacy of xenogeneic ADM dressings for the treatment of wounds in burn patients from the establishment of each database to December 2021. The outcome indexes included wound healing time, ratio of scar hyperplasia, Vancouver scar scale (VSS) score, ratio of complications, ratio of skin grafting, and ratio of bacteria detection. Rev Man 5.3 and Stata 14.0 statistical softwares were used to conduct a meta-analysis of eligible studies. Results: A total of 1 596 burn patients from 16 studies were included, including 835 patients in experimental group who received xenogeneic ADM dressings therapy and 761 patients in control group who received other methods therapy. The bias risk of all the 16 included studies was uncertain. Compared with those in control group, patients in experimental group had significantly shorter wound healing time, lower VSS scores (with standardized mean differences of -2.50 and -3.10, 95% confidence intervals of -3.02--1.98 and -4.87--1.34, respectively, P values both <0.05), and lower ratios of scar hyperplasia, complications, skin grafting, and bacteria detection (with relative risks of 0.58, 0.23, 0.32, and 0.27, 95% confidence intervals of 0.43-0.80, 0.14-0.37, 0.15-0.67, and 0.11-0.69, respectively, P<0.05). Subgroup analysis showed that the difference of intervention measures in control group might be the source of heterogeneity in wound healing time. There was no publication bias in ratio of scar hyperplasia (P≥0.05), while there was publication bias in wound healing time, VSS score, and ratio of complications (P<0.05). Conclusions: Xenogeneic ADM dressings can shorten the wound healing time of burn patients, reduce the VSS score and the ratios of scar hyperplasia, complications, skin grafting, and bacteria detection.

Features of different contemporary acupuncture and moxibustion schools in the treatment of post-stroke spastic paralysis / 中国针灸

Acupuncture and moxibustion has certain advantages in the treatment of post-stroke spastic paralysis，but the treatment methods and diagnosis and treatment ideas are complicated. This paper sortes out the representative contemporary acupuncture and moxibustion schools in the treatment of post-stroke spastic paralysis, analyzes their academic origins，summarizes and compares the theory，acupoint selection and technique characteristics of different schools in the diagnosis and treatment of this disease，so as to provide some references for guiding optimal treatment schemes selection in clinic.

Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis / 中国中药杂志

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.