Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study.

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

Construction and study of blood purification membrane modified with PDE inhibitor: Investigation of antiplatelet activity and hemocompatibility.

The recent "cell-based theory" of coagulation suggests that platelets serve as the site of coagulation factor reactions, making platelets an effective target for inhibiting membrane thrombosis. Unfortunately, there is limited research on how blood purification membranes affect platelet intracellular signaling. In this study, we modified polyethersulfone (PES) membranes with the platelet phosphodiesterase (PDE) inhibitor dipyridamole (DIP) and investigated the effects of the DIP/PES (DP) membranes on platelet adhesion, activation, aggregation, and secretion, as well as the role of the PDE-cyclic adenosine monophosphate (cAMP) intracellular signaling pathway. Additionally, we evaluated the hemocompatibility and preliminary in vivo safety of DP membranes. Our results demonstrate that the modified DP membranes effectively inhibited platelet adhesion, membrane CD62P expression, and plasma soluble P-selectin activation levels. Furthermore, we confirmed that DP membranes achieved platelet aggregation inhibition and reduced platelet factor 4 and ß-thromoglobulin secretion levels by inhibiting platelet intracellular PDE-cAMP signaling. Moreover, the modified DP membranes exhibited good anticoagulant and red blood cell membrane stability and complement resistance and demonstrated preliminary biocompatibility in mouse experiments. Collectively, these findings highlight the potential application of DP dialysis membranes in blood purification for critically ill patients.

Decreased placental TLR3 is associated with hepatitis B virus vaccine responsiveness in infants born to HBsAg-positive mothers.

Background: Although hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine. Methods: One hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group. Results: The TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ2=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)]. Conclusions: Decreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.

DNA methylation analysis reveals the effect of arsenic on gestational diabetes mellitus.

BACKGROUND: Arsenic (As) exposure is one of the risk factors for gestational diabetes mellitus (GDM). This study aimed to explore the effect of As-exposure on DNA methylation in GDM and to establish a risk assessment model of GDM in As exposed pregnant women. METHOD: We collected elbow vein blood of pregnant women before delivery to measure As concentration and DNA methylation data. Then compared the DNA methylation data and established a nomogram. RESULT: We identified a total of 10 key differentially methylated CpGs (DMCs) and found 6 corresponding genes. Functions were enriched in Hippo signaling pathway, cell tight junction, prophetic acid metabolism, ketone body metabolic process, and antigen processing and presentation. A nomogram was established that can predict GDM risks (c-index = 0.595, s:p = 0.973). CONCLUSION: We found 6 genes associated with GDM with high As exposure. The prediction of the nomograms has been proven to be effective.

Study on sustainable development of pharmaceutical health industry under ecological coordination.

Particularly in the post-pandemic period, where public health emergencies offer a greater risk of supply disruptions, the operational hazards of pharmaceutical supply chains are uncertain. One of the main concerns for businesses is how to handle the risk of supply disruption and take the necessary precautions to lower the chance of loss. Pharmaceutical raw material suppliers, pharmaceutical manufacturers and medical institutions constitute a complete three-tiered supply chain. On the basis of this, in Materials and methods part, a share contract based on buyback proceeds is created as a result, and a combination contract based on centralized decision-making and decentralized decision-making is employed to maximize the order volume of pharmaceutical supply chain participants. An out-of-stock cost pharmaceutical supply chain model is created, and a related solution is provided and measurable examples. In Results and discussion part, to confirm the accuracy of the model and algorithm, numerical examples are employed. Buyback prices and order volumes were subjected to sensitivity analysis, and discussion is had over how various parameters affect a model's performance. Due to supply disruptions, the study's findings show that there is "double sourcing" between upstream pharmaceutical raw materials and downstream major suppliers, necessitating the establishment of a supply chain with numerous standby suppliers. At the same time, modifying the contract parameters can improve the supply motivation of backup suppliers and guarantee the profitability of downstream medical institutions.

Emotion regulation strategies and PTSS among children who experienced an explosion accident: the moderating role of trait mindfulness.

The purpose of this study was to investigate the moderating role of trait mindfulness in the relationship between emotion regulation strategies and post-traumatic stress symptoms (PTSS) among children and adolescents who experienced an explosion accident. A total of 712 participants, aged 7-15, (Mage = 11.45, SD = 1.77; 48.9% male) who have experienced an explosion accident completed the Emotion Regulation Questionnaire, the Trauma Screening Questionnaire and the Mindful Attention Awareness Scale. The results showed that trait mindfulness significantly moderated the relationship of the expressive suppression and PTSS under the control of sex, age, trauma exposure, and cognitive reappraisal strategy (ß = -0.27, p < 0.05). However, the moderating effect of trait mindfulness between cognitive reappraisal strategy and PTSS was not significant (p> 0.05). Findings suggested that traumatized children with low levels of mindfulness may report severer PTSS when they adopt expressive suppression strategy.

Hemophagocytic lymphohistiocytosis as an onset of diffuse large B-cell lymphoma: A case report.

A 53-year-old male presented with a 1-month history of hyperpyrexia. The clinical manifestations revealed hemophagocytic lymphohistiocytosis (HLH). Although a lymph node biopsy could not be obtained, a bone marrow biopsy revealed the activated B-cell subtype of diffuse large B-cell lymphoma (DLBCL). After being treated with HLH-1994 (dexamethasone and etoposide), a rituximab-containing chemotherapy and target agents involving bortezomib, the patient achieved remission. To understand the molecular profile of patient, next-generation sequencing and MYD88 L265P mutation examinations were performed, and the patient was determined to be positive for the MYD88 L265P mutation. Reports of DLBCL with plasmacytic differentiation and a MYD88 innate immune signal transduction adaptor L265P mutation concurrent with HLH are rare. Early recognition, precise diagnosis and timely therapy are pivotal in improving patient prognosis. Furthermore, molecular profiling enables researchers to develop potential therapies aimed at the activated NF-κB and endoplasmic reticulum stress signaling pathways. The present study highlights this pathogenesis and provides suggestions for further individualized therapeutics.

Application of modified Matutes score containing CD200 in diagnosis of chronic lymphocytic leukemia. / 含CD200的改良型Matuteså ç–«æ ‡å¿—ç§¯åˆ†ç³»ç»Ÿåœ¨è¯Šæ–­æ ¢æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— ä¸­çš„åº”ç”¨.

OBJECTIVES: Immunophenotyping technique is a powerful tool for the diagnosis and differential diagnosis of chronic lymphocytic leukemia (CLL) and other B-cell chronic lymphoproliferative diseases (B-CLPD). CD200 is strongly expressed in CLL. This study aims to analyze the clinical value of modified Matutes score (MMS) containing CD200 in the diagnosis of CLL. METHODS: We retrospectively analyzed 103 B-CLPD patients diagnosed from January 2020 to July 2021, including 64 CLL patients, 11 follicular lymphoma (FL) patients, 14 mantle cell lymphoma (MCL) patients, 6 marginal zone lymphoma (MZL) patients, 1 hairy cell leukemia (HCL) patient, and 7 lymphoplasmic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) patients. The expression of CD markers between the CLL group and the non-CLL group was compared, and the sensitivity, specificity, and clinical consistency of MMS and Royal Marsden Hospital (RMH) immunophenotyping score system were analyzed. RESULTS: There were significant differences in the expressions of CD5, CD23, FMC7, CD22, CD79b, CD200, and sIg between the CLL group and the non-CLL group (χ2 values were 37.42, 54.98, 30.71, 11.67, 55.26, 68.48, and 17.88, respectively, all P<0.01). When the RMH immunophenotyping score≥4, the sensitivity was 79.7%, and the specificity was 100%. When the MMS≥3, the sensitivity was 95.3%, and the specificity was 100%. The Kappa coefficient of RMH immunophenotyping system was 0.677, and the Kappa coefficient of MMS system was 0.860. CONCLUSIONS: The MMS system containing CD200 has better sensitivity and same specificity compared with RMH immunophenotyping system, and MMS system may be more useful in the diagnosis of CLL.

Urinary incontinence and its association with pelvic floor muscle exercise among pregnant women attending a primary care clinic in Selangor, Malaysia.

BACKGROUND: Urinary Incontinence (UI) is when a person is unable to hold his/her urine effectively. This is a common problem which can develop and worsen during pregnancy. An effective way to manage UI is to educate patients on the Pelvic Floor Muscle Exercise (PFME) regularly. The present study aimed to ascertain the pregnant women's knowledge, attitudes, and practices (KAP) related to PFME. METHODS: This was a cross-sectional study done in a one primary care clinic located in a semi-urban area in Selangor, Malaysia. Simple random sampling was conducted among pregnant women aged 18 years old and above at any gestation. The validated study instruments used consisted of questions on socio-demography, KAP on UI, and also the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form to determine UI among the respondents. RESULTS: The response rate for this study was 72.1%, where 440 pregnant women consented to take part in the study. The median age of study respondents was 30 years old and majority of the study respondents was from the Malay ethnicity (80.9%). The prevalence of UI was 40.9%. The proportion of pregnant women with good knowledge, attitude and practice scores were 58.0%, 46.6% and 45.2% respectively. There was a significant association between UI and age (p = .03), body mass index (p = .03), ethnicity (p = .04), gravida. (p = .001), knowledge on PFME (p = .007) and attitude towards PFME (p = .006). CONCLUSIONS: Findings from this study fill a gap in the prevalence and KAP concerning PFME at the primary care level. The foundation areas for future education and health promotion on UI should address the importance of correct PFME. This education can be delivered through a pragmatic way to ensure its effectiveness and sustainability of the health promotion program.

Regenerative Medicine as a Potential and Future Intervention for Ankle Sprain

@#Ankle sprain is one of the most common injuries associated with physical activities. Complications including pain and ankle instability are associated with decreased physical activity, reduced sport performance, and increased risk of recurrent ankle injury leading to detrimental effect on activities of daily living. Current management of ankle sprain can be conservative or surgical for serious cases. However, long healing period is required for conservative management in addition to its side effects and the risk of post-operative complications for surgical management. Due to the current challenges and setbacks faced by existing intervention, this paper aims to generate ideas in incorporating regenerative medicine as an intervention for ankle sprain. This review will provide a brief review on the existing management for ankle sprain along with some history, application and the potential of regenerative medicine in speeding up the healing process of ankle sprains.

Quality of Life in Patients With Breast Cancer: The Influence of Family Caregiver's Burden and the Mediation of Patient's Anxiety and Depression.

Previous research showed that family caregiver's perception of burden can influence patient's report on their quality of life (QoL). The present study investigated the relationship between the two variables by considering the role of patient's anxiety and depression. A total of 382 dyads of Chinese breast cancer patients and their family caregivers participated in this study. The results showed that the mediation model fitted the data well (χ = 49.859; df = 16; χ/df = 3.116; RMSEA = 0.05; TLI = 0.928; CFI = 0.959). It indicated that family caregiver's burden influenced patient's QoL negatively, and this relationship was partially mediated by patient's anxiety and depression.

Dispositional mindfulness mediates the relations between neuroticism and posttraumatic stress disorder and depression in Chinese adolescents after a tornado.

Previous studies have shown that neuroticism is associated with higher levels of posttraumatic stress disorder (PTSD) and depression in individuals who have experienced traumatic events. This study investigated dispositional mindfulness as one pathway in which neuroticism is related to PTSD and depression symptoms among Chinese adolescents who have experienced trauma by considering the role of dispositional mindfulness. Participants were 443 Chinese adolescents who had experienced a severe tornado a year prior to this study. The results showed that our model fitted the data well (χ2/df = 2.113, comparative fit index (CFI) = 0.981, Tucker-Lewis index (TLI) = 0.969, root mean square error of approximation (RMSEA) (90% confidence interval (CI)) = 0.061 [0.047, 0.080]) and revealed that dispositional mindfulness partially mediated the relationship between neuroticism and PTSD and depression symptoms. The clinical implications and limitations of our research and recommendations for future research are discussed in this article.

Mindfulness, posttraumatic stress symptoms, depression, and social functioning impairment in Chinese adolescents following a tornado: Mediation of posttraumatic cognitive change.

Previous studies have shown that mindfulness is associated with less negative traumatic outcomes in people who experienced traumatic events. The present study investigated how mindfulness is related to posttraumatic stress disorders (PTSD) symptoms, depression and social functioning impairment in Chinese traumatized adolescents by considering the role of posttraumatic cognitive change (PCC). A total of 247 Chinese adolescents, who had experienced a severe tornado six months prior to this study, were recruited to complete a series of questionnaires. Results showed that the proposed model fitted the data very well (χ2 = 16.200, df = 8, χ2/df = 2.025, GFI = 0.983, CFI = 0.991, TLI = 0.976, RMSEA = 0.063). Further analyses revealed that PCC mediated the relation between dispositional mindfulness and all negative posttraumatic outcomes (including PTSD symptoms, depression and social functioning impairment). Limitations, clinical implications, and directions for future research were discussed.

A study of the stressors and coping behaviors of parents of Chinese hemophilic children.

To understand the stressors experienced by parents of hemophiliac children in China and the coping behaviors utilized, semi-structured interviews were conducted with parents of 158 Chinese hemophiliac children. We administered the Coping Health Inventory for Parents to determine coping behaviors. Parents' main stressors were in the domains of children's illness and physical condition, economic problems, and so on. Parents engaged in various positive coping behaviors to manage these stressors. The helpfulness of these coping behaviors in maintaining a normal family life differed significantly by parents' education and income ( p < .01). Parents of hemophilic children in China face numerous stressors but engage in a number of coping behaviors to manage these stressors. While treating hemophilic children, Chinese medical workers should guide parents to adopt such positive coping behaviors.

Clinical analysis of 42 cases of EBV-positive mature T/NK-cell neoplasms.

The pathogenesis of Epstein-Barr virus-positive (EBV+) mature T-cell and natural killer (NK)-cell neoplasms is challenging to understand. The clinical features are diverse, with no typical manifestation. Therefore, it is important to analyze the association of the clinical characteristics and prognoses of patients with various factors associated with EBV+ T/NK-cell neoplasms, particularly extranodal NK/T cell lymphoma, systemic EBV+ T/NK cell lymphoproliferative disorders, aggressive NK cell leukemia and EBV+ peripheral T-cell lymphoma. Therefore, 42 cases of EBV+ T/NK-cell neoplasms with information on age, gender, fever, LDH level, complete blood count (CBC) and immunophenotype (CD5/CD20) were retrospectively analyzed to examine the clinical features, prognoses and related factors. It was found that patients ≤60 years old accounted for 86% of cases. The frequency of stage III/IV disease was higher in groups with pancytopenia (P=0.005), high LDH level (P=0.020), CD5-expression status (P=0.031) and fever (P=0.024). There were significant differences in the mean International Prognostic Index (IPI) scores according to the presence or absence of fever (P=0.022), elevated or normal lactose dehydrogenase (LDH) levels (P=0.001), and pancytopenia or normal complete blood count (CBC; P=0.046). Analysis of overall survival showed that CD5 expression, CBC, IPI scores and LDH levels were factors associated with OS. CD5 expression (P=0.003), CBC (P=0.003) and IPI scores (P=0.017) were identified to be important risk factors on the basis of Cox regression analysis. The mean survival time was longer in the CD5+, CD20+ and normal CBC groups, and there was no clear difference in survival time according to LDH level or fever. In summary, CD5 and CD20 may be prognostic factors in EBV+ T/NK lymphoid neoplasms, and CBC and fever are most likely to influence the IPI score and Ann Arbor stage.

Effect of NPM1 type B mutation on the proliferation, invasion and chemosensitivity of THP-1 leukemia cells.

Acute myeloid leukemia (AML) is the most malignant myeloid disorder in adults. AML with mutated nucleophosmin (NPM1) is regarded as an independent leukemia subtype. According to previous studies, the role of NPM1 gene A mutation in AML has been well established; however, another major type, NPM1 gene B type mutation (NPM1 MutB) has been rarely reported. In the present study, we found that overexpression of NPM1 MutB enhanced the proliferation and invasion of THP-1 AML cells through the regulation of TIMP-2, MMP-2, Ang-1, c-myc and CCND1; led to no significant change of apoptosis rate with the absence of chemotherapy agents, while enhanced the chemosensitivity of THP-1 AML cells to chemotherapy agents DNR and Ara-C through the regulation of Bax, Bcl-2 and caspase-3. Further, we revealed that NPM1 MutB overexpression reduced the NF-κB activity of THP-1 cells upon drug treatment. Taken together, we demonstrated the detailed functions of NPM1MutB in THP-1 proliferation, invasion, apoptosis and chemo-sensitivity. We provided a novel understanding of prognosis of patients carrying the NPM1 B mutation.

[Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress and inflammatory response in Kupffer cells].

OBJECTIVE: To evaluate whether dexmedetomidine hydrochloride, an α(2)-adrenergic receptor agonist, can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells.
 METHODS: H(2)O(2)-induced oxidative damage model of Kupffer cell was established. Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h. MTT colorimetry was used to demonstrate the survival rate of Kupffer cells. The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and TNF-α in the culture medium were assessed by corresponding kits.
 RESULTS: Dexmedetomidine hydrochloride protected Kupffer cells from H(2)O(2)-induced oxidative damage, showing an increase in the cell survival rate while a decrease in LDH, MDA and TNF-α release in the culture supernatant. Yohimbine, an α(2)-adrenergic receptor antagonist, completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells. Yohimbine itself had no effect on H(2)O(2)-induced oxidative damage and inflammatory response.
 CONCLUSION: Dexmedetomidine hydrochloride can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells through activation of α(2)-adrenergic receptors.

Effect of dexmedetomidine pretreatment on lung injury following intestinal ischemia-reperfusion.

Reperfusion injury is tissue damage caused by the re-supply of blood following a period of ischemia in tissues. Intestinal ischemia-reperfusion injury (IRI) is an extremely common clinical event associated with distant organ injury. The intestine serves as the initial organ of multi-system organ dysfunction syndrome. It is extremely important to identify a method to protect against IRI, as it is a key factor associated with morbidity and mortality in patients. In the present study, the protective effects of pretreatment with dexmedetomidine hydrochloride were investigated. Rats were divided into six groups and models of intestinal ischemia were created in the five groups. Certain groups were pretreated with dexmedetomidine hydrochloride. The levels of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay in order to evaluate the injury. Tissue sections were stained with hematoxylin and eosin to visualize the damage. qPCR and western blotting were performed to examine the inflammatory status. Pretreatment with various doses of dexmedetomidine hydrochloride significantly reduced the pathological scores and the inflammatory reaction. The levels of TNF-α, IL-6, TLR4 and MyD88 were decreased in the dexmedetomidine hydrochloride treatment groups compared with those in the sham control and untreated ischemia reperfusion groups. The results of the present study indicate that pretreatment with dexmedetomidine hydrochloride may be a useful method of reducing the damage caused by IRI.