[Efficacy of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei].

Objective: To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP). Methods: In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS). Results: A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions: CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Bibliometric analysis of intestinal microbiota in diabetic nephropathy.

OBJECTIVE: The purpose of this study is to use bibliometrics to explore the research overview and research hotspots. MATERIALS AND METHODS: The relevant literature on intestinal flora and diabetic nephropathy in the Web of Science Core Collection was sorted out, and VOSviewer, CiteSpace, Scimago Graphica and other software were used to conduct data visualization analysis on the number of publications, countries, institutions, journals, authors, keywords and citations. RESULTS: A total of 124 relevant literatures were included. From 2015 to 2022, the number of published papers increased every year. The countries, institutions and journals that published the most articles in this field are China, Isfahan University Medical Science and Frontiers in Pharmacology. Liu Bicheng and Mirlohi Maryam are the authors with the most published articles in this field. The main keywords of research in this field are obesity, inflammation, oxidative stress, indoxyl sulfate, short-chain fatty acids (SCFAs) and Chinese herbal medicine. CONCLUSIONS: This is the first bibliometric analysis of diabetic nephropathy and gut microbiota, reporting hot spots and emerging trends. Obesity, inflammation, oxidative stress, indoxyl sulfate, SCFAs and Chinese herbal medicine are the main keywords of current research, and SCFAs and Chinese herbal medicine may be the hotspots of future research.

Farrerol Alleviates Hypoxic-Ischemic Encephalopathy by Inhibiting Ferroptosis in Neonatal Rats via the Nrf2 Pathway.

Farrerol (FA) is a traditional Chinese herbal medicine known for its anti-inflammatory and anti-oxidative properties in various diseases. Ferroptosis is an iron-dependent oxidative stress-induced cell death. It is characterized by lipid peroxidation and glutathione depletion and is involved in neuronal injury. However, the role of FA in inhibiting ferroptosis in hypoxic-ischemic encephalopathy (HIE) and its underlying mechanisms are not yet completely elucidated. This study aimed to investigate whether FA could mediate ferroptosis and explore its function and molecular mechanism in HIE. A neonatal rat model of HIE was used, and rats were treated with FA, ML385 (a specific inhibitor of nuclear factor erythroid 2-related factor 2 [Nrf2]), or a combination of both. Neurological deficits, infarction volume, brain water content, pathological changes, and iron ion accumulation in the brain tissues were measured using the Zea-Longa scoring system and triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), and Perls' staining. The expression levels of GSH-Px, MDA, SOD, and ROS in brain tissues were also evaluated. Western blot analysis was performed to analyze the expression of the Nrf2 pathway and ferroptosis-related proteins. The results showed that FA administration significantly reduced neuronal damage, infarct volume, cerebral edema, and iron ion accumulation and inhibited MDA and ROS levels while promoting GSH-Px and SOD levels. FA also increased the expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Moreover, the combination of ML385 and FA in HIE abolished the FA protective effects. Therefore, the study concludes that FA exerts a neuroprotective effect after HIE by inhibiting oxidative stress and ferroptosis via the Nrf2 signaling pathway.

Effects of dietary methionine supplementation from different sources on growth performance and meat quality of barrows and gilts.

Methionine is indispensable for growth and meat formation in pigs. However, it is still unclear that increasing dietary sulphur-containing amino acid (SAA) levels using different methionine sources affects the growth performance and meat quality of barrows and gilts. To investigate this, 144 pigs (half barrows and half gilts) were fed the control (100% SAA, CON), DL-Methionine (125% SAA, DL-Met)-supplemented, or OH-Methionine (125% SAA, OH-Met)-supplemented diets during the 11-110 kg period. The results showed that plasma methionine levels varied among treatments during the experimental phase, with increased plasma methionine levels observed following increased SAA consumption during the 25-45 kg period. In contrast, pigs fed the DL-Met diet had lower plasma methionine levels than those fed the CON diet (95-110 kg). Additionally, gilts fed the DL-Met or OH-Met diets showed decreased drip loss in longissimus lumborum muscle (LM) compared to CON-fed gilts. OH-Met-fed gilts had higher pH45min values than those fed the CON or DL-Met diets, whereas OH-Met-fed barrows had higher L45min values than those fed the CON or DL-Met diets. Moreover, increased consumption of SAA, regardless of the methionine source, tended to decrease the shear force of the LM in pigs. In conclusion, this study indicates that increasing dietary levels of SAA (+25%) appeared to improve the meat quality of gilts by decreasing drip loss and increasing meat tenderness.

[Brief introduction on compilation and editions of Yang ke xuan cui].

Yang ke xuan cui («¼) is a surgical work compiled by Chen Wenzhi () of the Ming Dynasty. There are few of research on the completion and author of the book. Based on the evidences in the local chronicles, the prefaces and postscripts of the book, it has been verified that the book was originally completed no later than 1591, and Chen Wenzhi passed away no later than 1623. After investigating the 6 editions collected by 8 institutions, a collection of 11 books in total, by comparing the characteristics and circulation relationship of each edition, two systems of circulation were sorted out: block-printed edition of Xu Xi () and review edition of Xu Dachun ().

[The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia].

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) µg/L, and 54% (14/26) of these patients had SF levels of ≥100 µg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) µg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 µg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

[Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy].

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

[Effects of three medical nutrition therapies for weight loss on metabolic parameters and androgen level in overweight/obese patients with polycystic ovary syndrome].

Objective: To investigate the effects of calorie-restricted diet (CRD), high protein diet (HPD), high protein, and high dietary fiber diet (HPD+HDF) on metabolic parameters and androgen level in overweight/obese patients with polycystic ovary syndrome(PCOS). Methods: Ninety overweight/obese patients with PCOS from Peking University First Hospital from October 2018 to February 2020 were given medical nutrition weight loss therapy for 8 weeks and were randomly divided into CRD group, HPD group, and HPD+HDF group, with 30 patients in each group. Body composition, insulin resistance, and androgen level were detected before and after weight loss, and the efficacy of three weight loss therapies was compared through variance analysis and Kruskal-Wallis H test. Results: Eight patients in CRD group quit because they could not strictly complete the follow-up, therefore at the end of weight loss, 22, 30, and 30 patients in CRD group, HPD group and HPD+HDF group, respectively, were included in the final analysis. The baseline ages of the three groups were (31±2) years, (32±5) years and (31±5) years, respectively (P=0.952). After weight loss, the relevant indicators in HPD group and HPD+HDF group decreased more than those in CRD group. The body weight of CRD group, HPD group and HPD+HDF group decreased by 4.20 (11.92, 1.80), 5.00 (5.10, 3.32) and 6.10 (8.10, 3.07) kg, respectively (P=0.038); BMI of the three groups decreased by 0.80 (1.70, 0.40), 0.90 (1.23, 0.50) and 2.20 (3.30, 1.12) kg/m2, respectively (P=0.002); homeostatic model assessment-insulin resistance(HOMA-IR) index decreased by 0.48(1.93, 0.05), 1.21(2.91, 0.18) and 1.22(1.75, 0.89), respectively (P=0.196); and free androgen index(FAI) decreased by 0.23(0.67, -0.04), 0.41(0.64, 0.30) and 0.44(0.63, 0.24), respectively (P=0.357). Conclusions: The three medical nutrition therapies can effectively reduce the weight of overweight/obese patients with PCOS, and improve insulin resistance and hyperandrogenism. Compared with CRD group, HPD group, and HPD+HDF group have better fat-reducing effect, and can better preserve muscle and basal metabolic rate while losing weight.

Three first records of stick insects attacking plants (Inseect: Phasmida) in Tibet / Três primeiros registros de insetos-pau atacando plantas (Inseect: Phasmida) no Tibet

Except for a few stick insects that are economically valuable, most species be considered to be forest pests, so it is extremely important to obtain plant host-use information of more stick insects. In this paper, the plant hosts of three species of stick insects were recorded for the first time. We also discovered these stick insects can feed upon the flowers or leaves of plants. Lopaphus unidentatus (Chen & He, 1995) (Phasmida: Lonchodidae) attacked Hypericum choisianum Wall. ex N. Robson, 1973 (Hypericaceae), Leurophasma dolichocercum Bi, 1995 (Phasmida: Aschiphasmatidae) attacked Antenoron filiforme (Thunb.) Roberty & Vautier, 1964 (Polygonaceae) and Megalophasma granulatum Bi, 1995 (Phasmida: Lonchodidae) attacked Debregeasia orientalis C. J. Chen, 1991 (Urticaceae). Finally, we were lucky enough to also obtain photographs of them mating and feeding.

Exceto por alguns insetos-pau que são economicamente valiosos, a maioria das espécies pode ser considerada praga florestal, por isso é extremamente importante obter informações sobre o uso de hospedeiros de plantas de mais insetos-pau. Neste artigo, as plantas hospedeiras de três espécies de bicho-pau foram registradas pela primeira vez. Também descobrimos que esses bichos-pau podem se alimentar de flores ou folhas de plantas. Lopaphus unidentatus (Chen & He, 1995) (Phasmida: Lonchodidae) atacou a parede de Hypericum choisianum. ex N. Robson, 1973 (Hypericaceae), Leurophasma dolichocercum Bi, 1995 (Phasmida: Aschiphasmatidae) atacou Antenoron filiforme (Thunb.) Roberty & Vautier, 1964 (Polygonaceae) e Megalophasma granulatum Bi, 1995 (Phasmida: Lonchodidae orientaled) atacou Chen, 1991 (Urticaceae). Finalmente, tivemos a sorte de também obter fotos deles se acasalando e se alimentando.

Understanding the Complex Interactions between Coffee, Tea Intake and Neurologically Relevant Tissues Proteins in the Development of Anxiety and Depression.

OBJECTIVES: Coffee and tea intake might be associated with psychiatry diseases. However, it is unclear whether the effect of coffee/tea on anxiety and depression depending on the different types of proteins. DESIGN: This was a cross-sectional study. SETTING: Our datasets were downloaded from online. PARTICIPANTS: Phenotypic and genotypic data for coffee intake(N=376,196) and tea intake (N=376,078) were derived from UK Biobank. GWAS data of proteins (N=1,537) from neurologically relevant tissues (brain, cerebrospinal fluid (CSF) and plasma) were obtained from a recently published study. MEASUREMENTS: Multivariate linear analysis was then used to evaluate the potential interaction effect between coffee/tea intake and proteins polygenetic risk score (PRS) on the risks of anxiety and depression controlling for age, sex, Townsend deprivation index (TDI), smoke, drinking and education level. RESULTS: 34 coffee intake-proteins interactions and 15 tea intake-proteins interactions were observed in anxiety individuals, such as coffee intake-c-Jun interaction (ß=0.0169, P=4.131×10-3), coffee intake-Fas interaction (ß=-0.0190, P=8.132×10-4), tea intake-sL-Selectin interaction (ß=0.0112, P=5.412×10-3) and tea intake-IL-1F6 (ß=0.0083, P=4.471×10-2). 25 coffee intake-proteins and 14 tea intake-proteins interactions were observed in depression individuals, including coffee intake- IL-1 sRI (ß=0.0171, P=4.888×10-3) and coffee intake-NXPH1 interaction (ß=0.0156, P=9.819×10-3), tea intake-COLEC12 interaction (ß=0.0127, P=3.280×10-3), and tea intake-Layilin interaction (ß=0.0117, P=7.926×10-3). CONCLUSIONS: Our results suggested the important role of multiple proteins in neurologically relevant tissues in the associations between coffee/tea intake and psychiatry diseases, providing entry points to explore the mechanisms underlying anxiety and depression.

[Clinical characteristics and prognosis analysis of 498 cases with drug-induced liver injury].

Objective: To determine the risk factors, clinical characteristics and treatment prognosis, so as to provide reference for clinicians to diagnose, treat and prevent drug-induced liver injury (DILI). Methods: Data of 712 confirmed DILI cases were collected from the Second Affiliated Hospital of Kunming Medical University between 2013 to 2019. Among them, 498 cases were included in the study. All patients medical history, clinical manifestations and classification, laboratory parameters, disease severity, and mortality rate were collected. Statistical analysis was performed using t-test, Mann-Whitney U test/Pearson χ2 test/Fisher's exact test or Spearman's rank test. Results: Among the suspicious drugs causing DILI, single medication accounted for 89.56%, mainly including traditional Chinese medicine (56.43%), anti-tumor and immunomodulatory agents (8.03%), anti-infective drugs (4.42%), antipyretic and analgesic drugs (4.22%) %), etc., while combination medication accounted for 10.44%. The clinical classification was dominated with hepatocyte injury (63.05%), and there was a statistically significant difference in clinical classification among age groups (P<0.001). Age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and total bile acid (TBA) had statistically significant difference among different suspicious drugs in DILI caused by different drug (P<0.001, 0.003, 0.001, <0.001 and <0.001). Laboratory test results showed that there were statistically significant differences in ALT, AST, ALP, γ-glutamyltransferase (GGT), TBA, international normalized ratio (INR), and eosinophils (P<0.001, <0.001, <0.001, 0.018, 0.003 and 0.019, respectively). Chronic hepatitis was more common in the 54 cases who completed histopathological examination of the liver biopsy. Fibrosis degree was higher in the Western medicine group than Chinese herbal medicine group (P<0.05), and the difference was statistically significant (P<0.05). 96.99% of DILI patients were cured or improved, and 3.01% of patients were uncured. Ordinal logistic regression analysis showed that GGT and INR were independent predictors of poor prognosis. Conclusions: Suspicious drugs for DILI are herbal/dietary supplements, anti-tumor and immunomodulatory, anti-infective, and antipyretic and analgesic. The most common clinical classification is hepatocyte injury. Most patients with DILI have a good prognosis after drug withdrawal and GGT and INR are independent predictors of poor prognosis.

Advances in physiological mechanisms of selenium to improve heavy metal stress tolerance in plants.

Selenium (Se) is a metalloid mineral nutrient for human and animal health. Plants are the main foodstuff source of the Se intake of humans. For plants, the addition of an appropriate amount of Se could promotes growth and development, and improves the tolerance to environmental stress, especially stress from some of heavy metals (HM) stress, such as cadmium (Cd) and mercury (Hg). This paper mainly reviews and summarizes the physiological mechanism of Se in enhancing HM stress tolerance in plants. The antagonistic effect of Se on HM is a comprehensive effect that includes many physiological mechanisms. Se can promote the removal of excessive reactive oxygen species and reduce the oxidative damage of plant cells under HM elements stress. Se participates in the regulation of the transportation and distribution of HM ions in plants, and alleviates the damage caused by of HM stress. Moreover, Se combine with HM elements to form Se-HM complexes and promote the production of phytochelatins (PCs), thereby reducing the accumulation of HM ions in plants. Overall, Se plays an important role in plant response to HM stress, but current studies mainly focus on physiological mechanism, and further in-depth study on the molecular mechanism is essential to confirm the participation of Se in plant response to environmental stress. This review helps to comprehensively understand the physiological mechanism of Se in plant tolerance against to HM stress of plants, and provides important theoretical support for the practical application of Se in environmental remediation and agricultural development.

[Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors].

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

[Evaluation of vestibular-evoked myogenic potential for functional integrity of the brain stem in Kennedy's disease].

Objective: To investigate whether vestibular-evoked myogenic potentials(VEMPs) can be used to assess brainstem involvement in patients with Kennedy's disease (KD). Method: This was a case-control study.Twenty consecutive patients with genetically confirmed KD and 20 age-and sex-matched healthy subjects were enrolled from November 2018 to September 2020.All subjects were tested for three types of VEMPs, including cervical VEMP (c-VEMP) recorded by the sternocleidomastoid muscle (parameter:p13, n23), masseter VEMP (m-VEMP) recorded by the masseter muscle(parameter: p11), and ocular VEMP (o-VEMP) recorded by the inferior oblique muscle (parameter n10, p15).The latency of each wave, interside peak latency and interpeak latency of c-VEMP, the corrected amplitude and amplitude asymmetry ratio were recorded. Bilateral sternocleidomastoid muscle (SCMM) electromyography (EMG) was performed. The spinal cord and bulbous muscular atrophy functional rating scale (SBMAFRS) was used for assessment. Results: The mean p13 latency of c-VEMP was (15.5±1.4)ms, which was longer than that of the control group[(13.3±0.9)ms](P<0.05); the mean n23 latency was(25.5±1.4)ms, which was also longer than that of the control group[(22.5±1.0)ms] (P<0.05); the difference of bilateral p13[(2.3±0.6)ms] was significantly higher than that of the control group(P<0.05). The abnormal rates of c-, m-, o-VEMP in KD patients were 75%(15/20), 30%(6/20) and 20%(4/20), respectively. There was a significant positive correlation between c-VEMP latency and course of disease in KD patients(left: r=0.715, 0.695, right: r= 0.708, 0.715, both P<0.05). However, c-VEMP latency was negatively correlated with SBMAFRS score (left: r=-0.701, -0.694, right: r=-0.644, -0.685, both P<0.05). Abnormal rates of SCMM EMG in KD group were as follows: 15%(3/20)of patients showed spontaneous potential in resting state and 45% (9/20) of patients exhibited simple recruitment. Conclusions: The c-VEMP latency is a sensitive tool for detecting lower brainstem involvement in patients with KD, and the degree of damage increases with prolongation of disease course. The o-and m-VEMP abnormalities indicate that some KD patients develop upper brainstem damage.

[Efficacy of 1 384 cases of peritoneal carcinomatosis underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy].

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

The mouse cortico-basal ganglia-thalamic network.

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington's disease.

Huntington's disease (HD) is a hereditary neurodegenerative disorder of the basal ganglia for which disease-modifying treatments are not yet available. Although gene-silencing therapies are currently being tested, further molecular mechanisms must be explored to identify druggable targets for HD. Cytoplasmic polyadenylation element binding proteins 1 to 4 (CPEB1 to CPEB4) are RNA binding proteins that repress or activate translation of CPE-containing transcripts by shortening or elongating their poly(A) tail. Here, we found increased CPEB1 and decreased CPEB4 protein in the striatum of patients and mouse models with HD. This correlated with a reprogramming of polyadenylation in 17.3% of the transcriptome, markedly affecting neurodegeneration-associated genes including PSEN1, MAPT, SNCA, LRRK2, PINK1, DJ1, SOD1, TARDBP, FUS, and HTT and suggesting a new molecular mechanism in neurodegenerative disease etiology. We found decreased protein content of top deadenylated transcripts, including striatal atrophy­linked genes not previously related to HD, such as KTN1 and the easily druggable SLC19A3 (the ThTr2 thiamine transporter). Mutations in SLC19A3 cause biotin-thiamine­responsive basal ganglia disease (BTBGD), a striatal disorder that can be treated with a combination of biotin and thiamine. Similar to patients with BTBGD, patients with HD demonstrated decreased thiamine in the cerebrospinal fluid. Furthermore, patients and mice with HD showed decreased striatal concentrations of thiamine pyrophosphate (TPP), the metabolically active form of thiamine. High-dose biotin and thiamine treatment prevented TPP deficiency in HD mice and attenuated the radiological, neuropathological, and motor HD-like phenotypes, revealing an easily implementable therapy that might benefit patients with HD.

Light quantum control of persisting Higgs modes in iron-based superconductors.

The Higgs mechanism, i.e., spontaneous symmetry breaking of the quantum vacuum, is a cross-disciplinary principle, universal for understanding dark energy, antimatter and quantum materials, from superconductivity to magnetism. Unlike one-band superconductors (SCs), a conceptually distinct Higgs amplitude mode can arise in multi-band, unconventional superconductors  via strong interband Coulomb interaction, but is yet to be accessed. Here we discover such hybrid Higgs mode and demonstrate its quantum control by light in iron-based high-temperature SCs. Using terahertz (THz) two-pulse coherent spectroscopy, we observe a tunable amplitude mode coherent oscillation of the complex order parameter from coupled lower and upper bands. The nonlinear dependence of the hybrid Higgs mode on the THz driving fields is distinct from any known SC results: we observe a large reversible modulation of resonance strength, yet with a persisting mode frequency. Together with quantum kinetic modeling of a hybrid Higgs mechanism, distinct from charge-density fluctuations and without invoking phonons or disorder, our result provides compelling evidence for a light-controlled coupling between the electron and hole amplitude modes assisted by strong interband quantum entanglement. Such light-control of Higgs hybridization can be extended to probe many-body entanglement and hidden symmetries in other complex systems.

[Moxa nitrogen content determination and its application in moxa floss grade identification].

Artemisia argyi samples were collected from different areas in Hubei Qichun and medicinal botanical garden of Hubei University of Traditional Chinese Medicine, and samples were purchased from different areas in Qichun medicinal market. The same method was used to prepare A. argyi samples from different areas into moxa floss of different leaf velvet ratio. The nitrogen content of A. argyi was determined by Kjeldahl method. The results show that there was an inverse relationship between the content of nitrogen and the level of the leaf velvet ratio grades of moxa floss and nitrogen content. Therefore, six functional models were established to illustrate the relationship between the grades of leaf velvet ratio and nitrogen content. The accuracy of the functional models was evaluated by ■. The cubic function model and exponential function model are selected as the best models and the formula is: Y_(grades)=-4.26 N~3+26.09 N~2-61.09 N+55.84, Y_(grades)=63.68×10~(-1.374N), with R~2 values of 0.976 5 and 0.969 6, respectively. The accuracy reached above 95% of the two function models when verified by laboratory-made moxa floss, while the accuracy of the models was 85.44% when verifed by commercial moxa floss. These results indicate that the model could be applied to the identification of the grades of moxa floss.

A combination of three probiotic strains for treatment of acute diarrhoea in hospitalised children: an open label, randomised controlled trial.

Acute diarrhoea continues to be a leading cause of morbidity, hospitalisation, and mortality worldwide, and probiotics have been proposed as a complementary therapy in the treatment of acute diarrhoea. The goal of this study is to assess the efficacy and safety of three combined probiotic strains, Bifidobacterium lactis Bi-07, Lactobacillus rhamnosus HN001, and Lactobacillus acidophilus NCFM, as an adjunct to rehydration therapy in treatment of acute watery diarrhoea in hospitalised children. Eligible diarrheal children were randomised into intervention group (IG, n=96, conventional treatment for diarrhoea in combination with probiotics) and control group (CG, n=98, conventional treatment for diarrhoea without probiotics). The primary assessments of this study were duration of diarrhoea and hospital stay and improvement in diarrhoea symptoms. Significantly more children in the IG showed improvements in diarrhoea (defined as a decrease of stool frequency to no more than four times per day and an improved stool consistency within 24-48 h after the treatment) than those in the CG (96.9 vs 79.6%, P<0.05). Children supplemented with the mixed strains had a 22.5 h shorter (121.4±13.7 h vs 143.9±19.8 h) mean duration of diarrhoea and 1.2 d shorter hospital stays (5.1±1.2 d vs 6.3±1.4 d) than children only receiving the rehydration therapy (P<0.05). The prevalence of constipation of children in the IG (3.1%) was markedly lower (P<0.05) than that of children in the CG (13.3%) after treatment. In conclusion, the mixture of three probiotic strains given to children aged 1-3 years resulted in shorter durations of diarrhoea and hospitalisation and a higher percentage of improved children.