BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

OBJECTIVE: To investigate the clinical characteristics and prognosis of primary pulmonary lymphoma (PPL). METHODS: The clinical data of 17 patients with PPL admitted to Gansu Provincial Hospital from January 2013 to June 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: The median age of the 17 patients was 56 (29-73) years old. There were 8 males and 9 females. According to Ann Arbor staging system, there were 9 patients with stage I-II and 8 patients with stage III-IV. There were 14 patients with IPI score of 0-2 and 3 patients with IPI score of 3-4. All 17 patients had symptoms at the initial diagnosis, most of the first symptoms were cough, and 6 patients had B symptoms.Among the 17 patients, there were 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, 1 case of gray zone lymphoma (GZL), and 3 cases of Hodgkin's lymphoma (HL). 15 patients received chemotherapy, of which 3 cases received autologous hematopoietic stem cell transplantation(ASCT) and 3 cases received radiotherapy; 2 patients did not receive treatment. The median number of chemotherapy courses was 6(2-8). The short-term efficacy was evaluated, 12 patients achieved complete remission (CR) and 3 patients achieved partial remission (PR). The age, pathological subtype, sex, Ann Arbor stage, β₂-microglobulin(β₂-MG) level, lactate dehydrogenase(LDH) level were not correlated with CR rate (P >0.05), while IPI score was correlated with recent CR rate (P < 0.05 ). The median follow-up time was 31(2-102) months. One of the 12 CR patients died of COVID-19, and the rest survived. Among the 3 patients who did not reach CR, 1 died after disease progression, while the other 2 survived. One of the 2 untreated patients died one year after diagnosis. Both the median progression-free survival (PFS) time and overall survival (OS) time of the 17 patients were both 31 (2-102) months. CONCLUSION The incidence of PPL is low, and the disease has no specific clinical manifestations, which is easily missed and misdiagnosed. The pathological subtypes are mainly MALT lymphoma and DLBCL, and the treatment is mainly combined chemotherapy. The IPI score is related to the treatment efficacy.
Humans ; Middle Aged ; Male ; Female ; Adult ; Prognosis ; Aged ; Lung Neoplasms/therapy* ; Retrospective Studies ; Neoplasm Staging ; Lymphoma/therapy* ; Lymphoma, Large B-Cell, Diffuse

Objective: To explore the prognostic value of circulating tumor DNA (ctDNA) testing in patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy, and to guide the prevention and subsequent treatment of CAR-T-cell therapy failure. Methods: In this study, 48 patients with R/R DLBCL who received CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2017 and March 2022 were included. Furthermore, ctDNA testing of 187 lymphoma-related gene sets was performed on peripheral blood samples obtained before treatment. The patients were divided into complete remission and noncomplete remission groups. The chi-square test and t-test were used to compare group differences, and the Log-rank test was used to compare the differences in survival. Results: Among the patients who did not achieve complete remission after CAR-T-cell therapy for R/R DLBCL, the top ten genes with the highest mutation frequencies were TP53 (41%), TTN (36%), BCR (27%), KMT2D (27%), IGLL5 (23%), KMT2C (23%), MYD88 (23%), BTG2 (18%), MUC16 (18%), and SGK1 (18%). Kaplan-Meier survival analysis revealed that patients with ctDNA mutation genes >10 had poorer overall survival (OS) rate (1-year OS rate: 0 vs 73.8%, P<0.001) and progression-free survival (PFS) rate (1-year PFS rate: 0 vs 51.8%, P=0.011) compared with patients with ctDNA mutation genes ≤10. Moreover, patients with MUC16 mutation positivity before treatment had better OS (2-year OS rate: 56.8% vs 26.7%, P=0.046), whereas patients with BTG2 mutation positivity had poorer OS (1-year OS rate: 0 vs 72.5%, P=0.005) . Conclusion: ctDNA detection can serve as a tool for evaluating the efficacy of CAR-T-cell therapy in patients with R/R DLBCL. The pretreatment gene mutation burden, mutations in MUC16 and BTG2 have potential prognostic value.
Humans ; Prognosis ; Receptors, Chimeric Antigen ; Circulating Tumor DNA/genetics* ; Feasibility Studies ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Lymphoma, Non-Hodgkin ; Mutation ; Cell- and Tissue-Based Therapy ; Retrospective Studies ; Immediate-Early Proteins ; Tumor Suppressor Proteins

OBJECTIVE: To analyze the clinical features and prognosis of patients with Castleman's disease (CD) and improve the diagnosis and treatment of CD. METHODS: Clinical data of patients diagnosed with CD by pathological biopsy in Gansu Provincial Hospital from January 2009 to November 2020 were retrospectively analyzed. According to clinical classification, the patients were divided into two groups: UCD (unicentric CD) group (n=20) and MCD (multicentric CD) group (n=9). The clinical manifestations, laboratory examination, treatment regimens, pathological examination and follow-up data were statistically analyzed. RESULTS: There were no significant differences in average age and gender ratio between UCD group and MCD group. In UCD patients, 80.0% were hyaline vascular type, and 20.0% were plasma cell type. In MCD patients, 33.3% were hyaline vascular type, 55.6% were plasma cell type, and 11.1% were mixed type. There was significant difference in pathological classification between the two groups (P=0.039). The UCD patients usually presented asymptomatic single lymph node enlargement with mild clinical symptoms, while the MCD patients were characterized by multiple superficial and deep lymph node enlargement throughout the body. The incidences of asthenia, splenomegaly, serous effusion in MCD group were higher than those in UCD group (P<0.05). Meanwhile, the incidences of anemia, hypoproteinemia, increased ESR, elevated serum globulin and elevated β₂-microglobulin were significantly higher than those in UCD group too (P<0.05). There was no significant difference in the incidences of abnormal WBC, PLT and elevated LDH between the two groups (P>0.05). Among 20 patients with UCD, 13 cases reached complete remission (CR), 1 case achieved partial remission (PR). Among 9 patients with MCD, 3 cases received CR and 4 cases received PR. CONCLUSION Patients with CD requires pathological examination for diagnosis. Patients with UCD show mild clinical symptoms, good surgical treatment effect and good prognosis. Patients with MCD have diversified clinical manifestations and relatively poor prognosis, and these patients require comprehensive treatment.
Humans ; Castleman Disease/therapy* ; Retrospective Studies ; Prognosis ; Splenomegaly ; Anemia

Moderate and deep sedation can effectively relieve or eliminate the pain and body discomfort during wound dressing change in pediatric burn patients, relieve anxiety, agitation, and even delirium of the children, reduce the metabolic rate of the children, make them in a quiet, comfortable, and cooperative state, which is conducive to the smooth completion of dressing change. This paper summarized the three aspects of moderate and deep sedation in pediatric burn patients, including the overview, main points of implementation, and effects, and further introduced the moderate and deep sedation medication regimens for different routes of administration, as well as the content of evaluation and monitoring. Suggestions on the prevention and management of related complications and the management of moderate and deep sedation implementation procedures were put forward, in order to provide references for the development of moderate and deep sedation for wound dressing change in pediatric burn patients in China.
Child ; Humans ; Bandages/adverse effects* ; Burns/therapy* ; Deep Sedation ; Pain/complications* ; Pain Management/methods*

Objective To explore the risk factors for intracranial infection in patients after neurosurgery,con-struct and validate a Nomogram prediction model.Methods Data of 978 patients who underwent neurosurgery in a hospital in Nanjing from January 1,2019 to December 31,2022 were retrospectively analyzed.Independent risk fac-tors were screened through logistic univariate and multivariate analyses.Modeling variables were screened through Lasso regression.A Nomogram model was constructed and internally validated by logistic regression.Effectiveness of the model was evaluated with receiver operating characteristic(ROC)curve,calibration curve and decision curve.Results Among 978 patients underwent neurosurgery,293 had postoperative intracranial infection,with an inci-dence of healthcare-associated infection of 29.96％.There was no significant difference in age,gender,proportion of coronary heart disease,cerebral infarction,diabetes and hypertension between the infected group and the non-in-fected group(all P＞0.05).Multivariate logistic analysis showed that postoperative intracranial hypertension,fe-ver,increased neutrophil percentage in blood routine examination,turbid cerebrospinal fluid,positive Pan's test,decreased glucose concentration,abnormal ratio of cerebrospinal fluid/serum glucose,positive microbial culture,absence of indwelling external ventricular drainage tubes,presence of indwelling lumbar cistern drainage tubes,use of immunosuppressive agents,and long duration of surgery were independent risk factors for postoperative intracra-nial infection in patients who underwent neurosurgery(all P＜0.05).Fifteen variables were screened out through Lasso regression.Fourteen variables were finally included for modeling after collinear screening,missing data impu-tation(random forest method)and checking pairwise interaction items.A Nomogram prediction model was con-structed,with the area under ROC curve,sensitivity,specificity,and accuracy of 0.885,0.578,0.896,and 0.704,respectively.Internal validation of the model was conducted.The modeling and validation groups presented similar effects.The calibration curve and decision curve also indicated that the model had good predictive efficacy.Conclusion The constructed Nomogram prediction model for postoperative intracranial infection after neurosurgery is scientific,and the prediction indicators are easy to obtain.The model presents with high stability,reliability,and application value,thus can provide reference for the assessment of postoperative intracranial infection after neuro-surgery.

Objective: To understand the improvement effect of Lycium barbarum polysaccharide (LBP) on the intestinal flora of mother mice during pregnancy and their offspring who experienced chronic stress, and provide new ideas for improving the effect of stress on the intestinal tract. Methods: From July to October 2019, 24 SPF-grade female SD rats were selected and divided into control group, stress group, and stress+LBP group, with 8 rats in each group. A chronic unpredictable mild stimulation model during pregnancy was established (21 days) , and 40 mg/kg LBP solution was administered by gavage on the 8th day of stress. Venous blood from the medial canthus of the female mice was collected on the 1st day before stress and on the 1st, 7th, 14th and 21st days, respectively. Cortisol was measured and corticosterone concentration was calculated. The fresh feces of famale mice after stress and 20-day postnatal offspring mice were collected, and Illumina Miseq sequencing technology, alpha diversity and community composition were used to analyze the diversity and structure of intestinal flora. Results: On the 7th and 14th days of stress, the plasma corticosterone concentration of female mice in the stress group and stress+LBP group was higher than that in the control group (P<0.05) . In the Alpha diversity of female mice, the Ace index of the stress group was lower than that of the control group (P<0.05) . The analysis of intestinal flora structure showed that at the species level, the proportions of Lachnospiraceae and Lactobacillus in the stress+LBP group were higher than those in the stress group and control group. At the order level, the proportion of Clostridiales in the stress+LBP group was higher than that in the stress group and lower than that in the control group, while the proportion of Lactobacillales was higher than that in the stress group and control group. In the Alpha diversity of the offspring group, the Shannon index, Ace index and Chao index of the stress+LBP offspring group were higher than those of the stress offspring group (P<0.05) . The proportion of Lactobacillus in the stress+LBP offspring group was higher than that in the control offspring group and stress offspring group, and the proportions of Lachnospiraceae and Ruminococcaceae in the stress+LBP offspring group were higher than those in the stress offspring group, the proportion of Bacteroidales in the stress+LBP offspring group was lower than that in the stress offspring group, and the proportion of Clostridiales in the stress+LBP offspring group was higher than that in the stress and control offspring groups. Conclusion: The intervention of LBP may improve the changes in the intestinal flora diversity, abundance and flora structure of mother mice and offspring caused by pregnancy stress, thereby maintaining the balance of intestinal flora.
Animals ; Corticosterone ; Drugs, Chinese Herbal/pharmacology* ; Female ; Gastrointestinal Microbiome ; Hydrocortisone ; Mice ; Pregnancy ; Rats ; Rats, Sprague-Dawley

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

Aim To evaluate the protective effect of α-asarone on microglials with cerebral ischemia/reperfusion injury by measuring the expression of polar transformation and related inflammatory proteins in BV2 cells in vitro and its mechanisms.Methods The cerebral ischemia/reperfusion injury BV2 cells were pretreated by α-asarone in vitro and simulated by OGD/R model.The effect of α-asarone on the viability of damaged cells in OGD/R model was determined by CCK-8; the morphological changes of cells were observed to analyze the general morphology of cells; the levels of proinflammatory factor IL-1β, IL-18 and anti-inflammatory factor IL-10, IL-4, and ROS activity secreted by BV2 cells were detected by ELISA; the protein expressions of TGF-β, TNF-α and inflammatory related protein NLRP3, caspase 1, p-NF-κB were detected by Western blot.Results The results of in vitro experiments were as follows: the activity of damaged cells in OGD/R model was significantly increased by α-asarone, with the increase of administration dose, the cells in the low, medium and high dose groups of α-asarone decreased, and the "amoeba-like" cells and the cell body were gradually became stereoscopic and full.From the results of cell morphology, it could be seen that α-asarone had a certain proliferative effect on normal cells; the release was significantly reduced of proinflammatory factor IL-1β, IL-18 and TNF-α in OGD/R injured BV2 cells pretreated with α-asarone, also increased the release of IL-10, IL-4 and TGF-β, with a dose-effect relationship, and the high dose(16 μmol·L-1)was the best; the expressions of inflammatory related protein NLRP3, caspase 1, NF-κB and ROS activity in injured cells of OGD/R model were significantly reduced after pretreatment with α-asarone.Conclusions α-asarone has a significant protective effect on cerebral ischemia/reperfusion injury, mainly by regulating ROS activity and inhibiting phosphorylation of NF-κB, in order to reduce the excessive activation of NLRP3 inflammatory corpuscles reducing the secretion of proinflammatory factor IL-1β and IL-18, promoting the secretion of anti-inflammatory factor IL-10 and IL-4, so as to protect cerebral ischemia/reperfusion injury by anti-inflammatory reaction.

Objective:To summarize the experience of surgical treatment of primary liver cancer.Methods:The clinical data of 10 966 surgically managed cases with primary liver cancer, from January 1986 to December 2019 at Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The life table method was used to calculate the survival rate and postoperative recurrence rate. Log‐rank test was used to compare the survival process of different groups, and the Cox regression model was used for multivariate analysis. In addition, 2 884 cases of hepatocellular carcinoma(HCC) with more detailed follow‐up data from 2009 to 2019 were selected for survival analysis. Among 2 549 patients treated with hepatectomy, there were 2 107 males and 442 females, with an age of (56.6±11.1) years (range: 20 to 86 years). Among 335 patients treated with liver transplantation, there were 292 males and 43 females, with an age of (51.0±9.7) years (range: 21 to 73 years). The outcomes of hepatectomy versus liver transplantation, anatomic versus non-anatomic hepatectomy were compared, respectively.Results:Of the 10 966 patients with primary liver cancer, 10 331 patients underwent hepatectomy and 635 patients underwent liver transplantation. Patients with liver resection were categorized into three groups: 1986－1995(712 cases), 1996－2008(3 988 cases), 2009?2019(5 631 cases). The 5‐year overall survival rate was 32.9% in the first group(1986－1995). The 5‐year overall survival rate of resected primary liver cancer was 51.7% in the third group(2009‐2019), among which the 5‐year overal survival rates of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%, 26.6% and 50.6%, respectively. Further analysis was performed on 2 549 HCC patients with primary hepatectomy. The 1‐, 3‐, 5‐, and 10‐year overall survival rates were 88.1%, 71.9%, 60.0%, and 41.0%, respectively, and the perioperative mortality rate was 1.0%. Two hundred and forty‐seven HCC patients underwent primary liver transplantation, with 1‐, 3‐, 5‐, and 10‐year overall survival rates of 84.0%, 64.8%, 61.9%, and 57.6%, respectively. Eighty‐eight HCC patients underwent salvage liver transplantation, with the 1‐, 3‐, 5‐, and 10‐year overall survival rates of 86.8%, 65.2%, 52.5%, and 52.5%, respectively. There was no significant difference in survival rates between the two groups with liver transplantation ( P>0.05). Comparing the overall survival rates and recurrence rates of primary hepatectomy (2 549 cases) with primary liver transplantation (247 cases), the 1‐, 3‐, 5‐, and 10‐year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%, 87.1%, 76.9%, 54.7%, and 95.4%, 79.4%, 77.4%, 71.7%, respectively ( P=0.754). The 1‐, 3‐, 5‐year recurrence rates were 16.3%, 35.9%, 47.6% and 8.1%, 11.7%, 13.9%, respectively( P<0.01). The 1‐, 3‐, 5‐, 10‐year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%, 65.9%, 53.0%, 33.0% and 87.6%, 71.8%, 71.8%, 69.3%, respectively( P=0.003); the 1‐, 3‐, 5‐year recurrence rate were 39.2%, 57.8%, 69.7% and 29.7%, 36.7%, 36.7%, respectively ( P<0.01). The 1‐, 3‐, 5‐, and 10‐year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%, 36.1%, 22.2%, 15.0% and 62.9%, 31.8%,19.9%, 0, respectively ( P=0.387); the 1‐, 3‐, 5‐year recurrence rates were 61.5%, 74.7%, 80.8% and 59.7%, 82.9%, 87.2%, respectively( P=0.909). Independent prognostic factors for both overall survival and recurrence‐free survival rates of HCC patients treated with liver resection included gender, neoadjuvant therapy, symptoms, AST, intraoperative or postoperative blood transfusion, tumor number, tumor size, cirrhosis, macrovascular invasion, microvascular invasion, and pathological differentiation. Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non‐anatomical liver resection( P=0.895), but the recurrence rate of non‐anatomical liver resection was higher than that of anatomical liver resection( P=0.035). Conclusions:In the past decade, the overall survival rate of HCC undergoing surgical treatment is significantly higher than before. For HCC patients with good liver function reservation, surgical resection can be performed first, and salvage liver transplantation can be performed after recurrence. The effect of salvage liver transplantation is comparable to that of primary liver transplantation. As for the choice of liver resection approaches, non‐anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.