Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Value of the imaging features of extrapancreatic nerve plexus in predicting the early postoperative recurrence of ductal adenocarcinoma of pancreatic head / 中华肝胆外科杂志

Objective:To study the value of imaging features of extrapancreatic nerve plexus in predicting early postoperative recurrence of ductal adenocarcinoma of pancreatic head.Methods:The clinical, imaging and pathological data of patients with ductal adenocarcinoma of pancreatic head undergoing pancreati-coduodenectomy at the Hepatobiliary Pancreatic Center of Beijing Tsinghua Changgung Hospital, Tsinghua University from January 2014 to April 2022 were retrospectively analyzed. A total of 73 patients were included, including 51 males and 22 females, aged (66.1±9.0) years old. The patients were followed up by telephone or outpatient review, who were divided into two groups according to the recurrence within 6 months after surgery: the recurrence group ( n=26) and the non-recurrence group ( n=47). Streaks or soft-tissue densities in the distribution area of extrapancreatic nerve plexus, difference in CT values between the portal and arterial phases of the distribution area of extrapancreatic nerve plexus, maximum tumor diameter, and regional lymph node enlargement were compared between the two groups. Results:The incidences of streaks or soft-tissue densities showing in the distribution area of extrapancreatic nerve plexus were 80.8%(21/26) in the recurrence group and 51.1%(24/47) in the non-recurrence group, respectively. A CT value difference ≥15 HU between the portal and arterial phases of the distribution area of extrapancreatic nerve plexus occurred in 50.0%(13/26) patients of the recurrence group and 25.5%(27/47) of the non-recurrence group, respectively. Maximum tumor diameter ≥25 mm were found in 80.8% (21/26) patients of the recurrence group and 57.4% (27/47) of the non-recurrence group, respectively. ≥3 reginal lymph node enlargement showed in 65.4% (17/26) patients of the recurrence group and 31.9% (15/47) of the non-recurrence group, respectively (all P<0.05). The risk of early postoperative recurrence increased in patients with a CT value difference ≥15 HU between the portal and arterial phases of the distribution area of extrapancreatic nerve plexus ( OR=3.609, 95% CI: 1.099-11.855), and regional lymph node enlargement ≥ 3 ( OR=4.665, 95% CI: 1.400-15.545) (all P<0.05). And these two independent risk factors were combined to predict early postoperative recurrence of ductal adenocarcinoma of pancreatic head with an area under receiver operating characteristic curve of 0.748, sensitivity of 92.3%, and specificity of 48.9% ( P<0.001). Conclusion:≥ 15 HU CT value difference between the portal and arterial phases of the distribution area of extrapancreatic nerve plexus and ≥ 3 regional lymph node enlargement are independent risk factors for the early postoperative recurrence of pancreatic head ductal adenocarcinoma, which could provide more predictive information preoperatively.

Efficacy of Yupingfeng granule combined with cetirizine in the treatment of allergic rhinitis and its effects on serum inflammatory factor level / 中国基层医药

Objective:To investigate the efficacy of Yupingfeng granule combined with cetirizine in the treatment of allergic rhinitis and its effects on serum inflammatory factor level. Methods:A total of 162 patients with allergic rhinitis admitted to Zhejiang Provincial Hospital of Chinese Medicine from January 2021 to March 2022 were included in this prospective controlled study. They were randomly divided into a control group and an observation group ( n = 81/group). The control group was treated with cetirizine and the observation group was treated with Yupingfeng granule combined with cetirizine. All patients were treated for 4 weeks. Clinical efficacy was compared between the two groups after 4 weeks of treatment. Main symptom score, nasal function indexes (total nasal airway resistance, nasal minimal cross-sectional area, and 0-5 cm nasal cavity volume), levels of inflammatory factors (interleukin-4, interleukin-6, and interleukin-10), and Rhinoconjunctivitis Quality of Life Questionnaire scores were compared between the two groups before and after 4 weeks of treatment. Results:Total response rate in the observation group was significantly higher than that in the control group [92.59% (75/81) vs. 79.01% (64/81), χ2 = 6.13, P < 0.05]. After 4 weeks of treatment, the scores of nasal congestion, nasal itching, and sneezing in the observation group were (0.63 ± 0.20) points, (0.70 ± 0.21) points, and (0.54 ± 0.17) points, which were significantly lower than (1.07 ± 0.23) points, (1.08 ± 0.24) points, and (0.89 ± 0.22) points in the control group ( t = 12.99, 10.72, 11.33, all P < 0.05). After 4 weeks of treatment, total nasal airway resistance in the observation group was significantly lower than that in the control group [(0.17 ± 0.05) kPa·s -1·L -1vs. (0.26 ± 0.06) kPa·s -1·L -1, t = 10.37, P < 0.05]. Nasal minimal cross-sectional area and 0-5 cm nasal cavity volume in the observation group were (0.94 ± 0.17) cm 2 and (9.74 ± 0.89) cm 3, respectively, which were significantly higher than (0.76 ± 0.10) cm 2 and (8.43 ± 0.78) cm 3 in the control group ( t = 8.21, 9.96, both P < 0.05). After 4 weeks of treatment, serum levels of interleukin-4 and interleukin-6 in the observation group were (67.79 ± 9.94) ng/L and (6.74 ± 1.42) ng/L, respectively, which were significantly lower than (104.31 ± 14.45) ng/L and (10.29 ± 2.56) ng/L in the control group ( t = 18.74, 10.91, both P < 0.05). Serum level of interleukin-10 in the observation group was significantly higher than that in the control group [(17.97 ± 2.54) ng/L vs. (12.48 ± 2.46) ng/L, t = 13.97, P < 0.05]. After 4 weeks of treatment, Rhinoconjunctivitis Quality of Life Questionnaire score in the observation group was significantly lower than that in the control group [(27.43 ± 8.82) points vs. (38.95 ± 7.76) points, t = 8.82, P < 0.05). Conclusion:Yupingfeng granule combined with cetirizine is highly effective on allergic rhinitis. The combined therapy can reduce clinical symptoms and inflammatory reactions, improve nasal function, and thereby improve quality of life.

Comprehensive chemical profiling and quantitative analysis of ethnicYi medicine Miao-Fu-Zhi-Tong granules using UHPLC-MS/MS / 中国天然药物

Developing analytical methods for the chemical components of natural medicines remains a challenge due to its diversity and complexity. Miao-Fu-Zhi-Tong (MFZT) granules, an ethnic Yi herbal prescription, comprises 10 herbs and has been clinically applied for gouty arthritis (GA) therapy. Herein, a series of chemical profiling strategies including in-house library matching, molecular networking and MS/MS fragmentation behavior validation based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were developed for qualitative analysis of MFZT granules. A total of 207 compounds were identified or characterized in which several rare guanidines were discovered and profiled into alkyl substituted or cyclic subtypes. Moreover, network pharmacology analysis indicated that MFZT's anti-gout mechanism was mostly associated with the nuclear factor kappa-B (NF-κB) signaling, nucleotide oligomerization domain (NOD)-like signaling and rheumatoid arthritis pathways, along with the synergistic effect of 84 potential active compounds. In addition, a quantitative analytical method was developed to simultaneously determine the 29 potential effective components. Among them, berberine, pellodendrine, 3-feruloylquinic acid, neoastilbin, isoacteoside and chlorogenic acid derivatives at higher concentrations were considered as the chemical markers for quality control. These findings provide a holistic chemical basis for MFZT granules and will support the development of effective analytical methods for the herbal formulas of natural medicines.

Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain / 神经科学通报·英文版

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.

The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse / 神经科学通报·英文版

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.

A multicenter survey of critical neonatal care centers construction and treatment of critically-ill neonates at city- and county-level in Henan Province / 中国新生儿科杂志

Objective:To study the current status of critical neonatal care centers (CNCC) construction and treatment of critically-ill neonates at city- and county-level in Henan Province.Methods:A questionnaire survey was conducted in January 2022 to city- and county-level CNCC in Henan Province. The basic information of CNCC, ward settings, neonatal management in the Department of Obstetrics and the treatment of critically-ill neonates in 2019-2021 were analyzed.Results:A total of 188 questionnaires were sent and 183 (97.3%) eligible questionnaires were analyzed, including 30 from city centers and 153 from county centers. The bed occupancy rate in county centers was significantly lower than city centers (67.3%±24.1% vs. 86.1%±23.2%), and the doctor/bed ratio, doctor/rescue bed ratio and nurse/rescue bed ratio were significantly higher than city centers ( P<0.05). All city centers had set up independent Department of Neonatology and the number is 92.8% (142/153) in county center. For 80.9% (148/183) centers, neonates were managed in the Department of Obstetrics with consultations and referrals to the Department of Pediatrics and 19.1% (35/183) were managed in the Department of Pediatrics/Neonatology. The average number of deliveries and admissions to the Department of Neonatology in both city and county centers decreased year on year during 2019-2021, but the proportion of premature and low/very low birth weight infants treated in these centers increased year on year. During 2019-2021, the top three diseases treated at the city centers were neonatal respiratory distress syndrome, neonatal asphyxia and acute respiratory distress syndrome, while the top three diseases treated at the county centers were neonatal asphyxia, neonatal respiratory distress syndrome and meconium aspiration syndrome. The incidence of sudden infant death syndrome in city and county centers was (10~30)/100,000. Conclusions:The construction of CNCC in Henan Province is facing challenges such as decreased hospital admissions, increased critically-ill neonates, insufficient cooperation between Obstetrics and Pediatrics and waste of resources. Rationally allocated and optimised use of resources to improve the ability to treat critically-ill neonates is warranted.

Effects of recombinant human erythropoietin on cerebral blood flow in preterm infants: arterial spin labeling magnetic resonance imaging evaluation / 中国新生儿科杂志

Objective:To study the effects of recombinant human erythropoietin (rhEPO) on cerebral blood flow (CBF) in preterm infants using arterial spin labeling (ASL) magnetic resonance imaging (MRI).Methods:From September 2021 to June 2022, preterm infants (gestational age ≤32 weeks, birth weight ≤1 500 g) admitted to NICU of our hospital within 24 h after birth were randomly assigned into rhEPO group and control group for this prospective study. The rhEPO group was given rhEPO (500 IU/kg iv, once every other day for 2 weeks) within 72 h after birth plus symptomatic supportive treatment. The control group received same amount of normal saline injection. Both groups received brain MRI, diffusion-weighted imaging and ASL at adjusted gestational age of 35~37 weeks and CBF values of interested areas were measured.Results:A total of 85 infants were enrolled, including 40 in the rhEPO group and 45 in the control group. No significant differences existed in the incidences of periventricular-intraventricular hemorrhage, periventricular leukomalacia, focal white matter injury and extensive white matter injury between the two groups ( P>0.05). The CBF values [ml/(100 g·min)] of frontal cortex [left 15.1±3.9 vs. 17.9±3.1, right 15.9 (12.5, 17.8) vs. 18.1(16.1,20.2)], temporal cortex [left 15.8±4.3 vs. 18.6±3.8, right 16.3(13.2,19.4) vs. 18.1(15.7,19.7)], occipital cortex (left 15.8±6.1 vs. 18.8±3.3, right 16.8±5.5 vs. 19.3±4.8), basal ganglia (left 24.7±7.2 vs. 28.7±6.2, right 26.0±7.9 vs. 29.3±6.4) and thalamus (left 32.7±11.8 vs. 37.9±8.6, right 32.1±11.6 vs. 37.6±10.2) in the rhEPO group were significantly lower than the control group ( P<0.05). No significant differences existed of CBF value at the parietal cortex between the two groups ( P>0.05). Conclusions:Early application of rhEPO can reduce CBF in premature infants, which may be related to the neuro-protective effects of EPO.

Neonatal Smith-Kingsmore syndrome: case report and literature review / 中国新生儿科杂志

Objective:To study the clinical and genetic features of neonatal Smith-Kingsmore syndrome (SKS).Methods:The clinical data of a newborn with SKS admitted to our hospital in November 2021 were reviewed. Using "Smith-Kingsmore", "rapamycin gene", "newborn", "premature infant", "the mammalian target of rapamycin", "MTOR", "mTOR", "Smith-Kingsmore syndrome", "megalencephaly", "macrocephaly" and "hemimegalencephaly" as keywords, databases including CNKI, Wanfang Database, VIP database, PubMed, Embase, Web of Science and the Cochrane Library were searched from the date of establishment to January 1, 2022. The clinical and genetic features of neonatal SKS from published literature were summarized.Results:The case admitted to our hospital was a male preterm infant. The presenting symptoms were groan and hypotonia. The facial abnormalities included macrocrania, ocular hypertelorism, depressed nasal bridge and low-set ears. Brain MRI showed lateral ventricle enlargement. Whole-genome sequencing (WGS) showed mTOR gene nonsense heterozygous mutation (NM_004958.4:c.7255G>A:p.Glu2419Lys). Neither father nor mother had any pathogenic gene mutations. The infant had seizure at 2-month and phenobarbital was effective reducing seizure. Gross motor delay was present at 3-month. Sixteen related articles were retrieved, including eight articles with 10 neonatal cases. Among them, 6 cases were male. The main clinical features were megalencephaly or hemimegalencephaly (9/10), facial developmental malformation (8/10), hypotonia (6/10), large-for-gestational age (LGA) infants (5/10), cerebral ventricle dilation (4/10) and abnormal corpus callosum (4/10). All the gene mutations were missense mutations, including c.5395G>A(p.Glu1799Lys) mutation in 5 cases, c.4448G>T(p.Cys1483Phe) mutation in 1 case, c.4448G>T(p.Cys1483Tyr) mutation in 1 case, c.7235A>T(p.Asp2412Val) mutation in 1 case, c.5663T>G(p.Phe1888Cys) mutation in 1 case, c.5390C>T(p.Thr1799IIe) mutation in 1 case.Conclusions:The clinical phenotypes of neonatal SKS are diverse, including megalencephaly, facial malformation, LGA and hypotonia. The brain MR findings included (hemi) megalencephaly, cerebral ventricle dilation and corpus callosum hypoplasia. Most of the gene mutations are missense mutations and c.5395G>A(p.Glu1799Lys) is the hotspot.

Treatment progress of relapsed/refractory peripheral T-cell lymphoma / 白血病·淋巴瘤

Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous disease with numerous subtypes, and the overall prognosis is poor, especially in relapsed/refractory patients, and the patients are generally older with limited treatment options that can be tolerated. At the 64th American Society of Hematology (ASH) Annual Meeting in 2022, studies on relapsed/refractory PTCL include the combination of epigenetic agents or combination of immune checkpoint inhibitors, CD30 antibody-drug conjugate (ADC) brentuximab vedotin combined with chemotherapy, targeted drugs PI3K inhibitors and JAK1 inhibitors, etc., providing more choices and opportunities for relapsed/refractory patients.

Systematic review and Meta-analysis of efficacy and safety of Tangmaikang Granules in treatment of diabetic peripheral neuropathy / 中国中药杂志

This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.

Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis / 生物医学与环境科学（英文）

OBJECTIVE@#This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism.@*METHODS@#The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model.@*RESULTS@#RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice.@*CONCLUSION@#Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.

Overview and reflection on the development of the first batch of the inheritance studios of acupuncture and moxibustion academic schools / 中国针灸

The development status of the first 11 inheritance studios of acupuncture and moxibustion academic schools is summarized. Aiming at the current problems, it is suggested to establish qualitative and quantitative evaluation standards and establish a fair and reasonable evaluation system, build a systematic scientific theory and excavate the inherent laws of the schools, implement standardized management of the schools and protect the personalized characteristics of the schools, open outpatient clinic of acupuncture and moxibustion schools and promote the characteristic diagnosis and treatment technology, to promote the inheritance and development of acupuncture and moxibustion academic schools.

Brief introduction of Qilu modern acupuncture methods / 中国针灸

Qilu acupuncture and moxibustion has promoted the formation and development of traditional Chinese medicine, which has a special historical position. By systematically collecting, sorting out and summarizing the characteristic acupuncture methods and academic ideas of several Qilu acupuncturists since the founding of the People's Republic of China, the understanding of the advantages and characteristics of Qilu modern acupuncture methods is deepened, aiming to exploring the inheritance and development pattern of Qilu acupuncture methods in the new era.

The efficacy and side effects of rigosertib combined with chemotherapy in KRAS mutant colorectal cancer mice / 中华肿瘤杂志

Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.

Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.

Chemical Constituent Analysis of Tongxie Yaofang Decoction by UPLC-LTQ-Orbitrap-MS / 中国实验方剂学杂志

ObjectiveTo rapidly identify the chemical constituents in Tongxie Yaofang decoction by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap-MS）. MethodChromatographic conditions were ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm）， mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution （0-4 min， 5%-15%B； 4-10 min， 15%-25%B； 10-15 min， 25%-60%B； 15-20 min， 60%-90%B； 20-25 min， 90%-100%B； 25-27 min， 100%B； 27-30 min， 100%-5%B； 30-32 min， 5%B）， flow rate of 0.3 mL·min-1， column temperature at 35 ℃ and injection volume of 3 μL. UPLC-LTQ-Orbitrap-MS was equipped with an electrospray ionization（ESI）， the MS and MS/MS data were collected in positive and negative ion modes， and detection range was m/z 100-1 250. Combining the reference substance， chemical databases and related literature information， TraceFinder 4.1 and Xcalibur 2.1 were used to identify the chemical constituents of Tongxie Yaofang decoction. ResultA total of 90 compounds， mainly including flavonoids， coumarins， monoterpene glycosides， chromones and lactones， were identified from Tongxie Yaofang decoction. By attributing the sources of Chinese medicines for all identified compounds， 9 of them were found to be derived from Atractylodis Macrocephalae Rhizoma， 21 from Paeoniae Radix Alba， 24 from Citri Reticulatae Pericarpium， 29 from Saposhnikoviae Radix， and 7 from at least two Chinese medicines. ConclusionThe method can effectively， quickly and comprehensively identify the chemical components of Tongxie Yaofang decoction， and clarify the chemical composition. These identified compounds cover the main active ingredients of the four herbs with high abundance， which indicates that the extraction method and the ratio of the medicinal materials of Tongxie Yaofang are scientific， and can provide a reference for the research on the material basis and quality evaluation of this famous classical formula.

Effect of experiential health education on diet control of college students with type 2 pre diabetes mellitus / 中国学校卫生

Objective@#To understand the influence of experiential health education on diet control of college students with pre diabetes mellitus, and to provide reference for healthy eating habits promotion among college students.@*Methods@#According to the method of random number table, 78 pre diabetic college students screened from Changzhi Medical College from September 2020 to June 2021 were randomly assigned to observation group and control group (39 students in each group). The control group received routine health education for 10 months, once a week for 1 hour each time; On the basis of the above, the observation group received experiential health education once a week for 1 hour, including diet experience, exercise experience, blood sugar test experience and chronic complications experience. Blood glucose and lipids level, body mass index (BMI), dietary control as well as the stages of change for dietary control behavior were compared between the two groups.@*Results@#There was significant difference between the observation group and the control group in the stages of change for dietary control behavior 10 months after intervention ( χ 2=8.92, P <0.05). The compliance score of the observation group was significantly higher than that of the control group in the same period 10 months after the intervention ( t =3.74, P <0.01), the score of the knowledge of diet control in the observation group 10 months after intervention was significantly higher than that in the control group ( t =11.51, P <0.05). The levels of BMI, TG and TC in the observation group were significantly lower than those in the control group at 5 and 10 months after intervention, and the differences were statistically significant ( P <0.05).@*Conclusion@#Experiential health education helps to promote awareness of diabete related knowledge, enhance self management behavior and good diet control habits, and is effective for blood glucose control.

A rationally designed cancer vaccine based on NIR-II fluorescence image-guided light-triggered remote control of antigen cross-presentation and autophagy

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

Noninvasive Tracking of Every Individual in Unmarked Mouse Groups Using Multi-Camera Fusion and Deep Learning / 神经科学通报·英文版

Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions. Traditional tracking methods (e.g., marking each animal with dye or surgically implanting microchips) can be invasive and may have an impact on the social behavior being measured. To overcome these shortcomings, video-based methods for tracking unmarked animals, such as fruit flies and zebrafish, have been developed. However, tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns. In this study, we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network (R-CNN) deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology. The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior. The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.