Objective:To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal natural killer (NK) /T cell lymphoma (ENKTL) .Methods:A retrospective analysis was performed on sixty early-stage ENKTL patients treated with the P-GemDOx regimen who were admitted to the First Affiliated Hospital of Nanjing Medical University between August 2015 and May 2021. The Chi-square test or Fisher's exact test was used to compare group differences, and the Log-rank test was used to compare the differences in survival. Survival outcomes and prognostic factors were examined.Results:After completing 4 to 6 cycles of P-GemDOx chemotherapy, the overall response rate (ORR) was 88.3%, with forty-six patients (76.7% ) achieving complete response (CR). The 4-year progression-free survival (PFS) and overall survival (OS) rates were (66.3±7.1) % and (79.5±6.0) %, respectively. According to the PINK/PINK-E model, there was no significant difference in survival outcomes among risk groups. 23.3% of patients experienced progression of disease within 24 months (POD<24). OS estimates differed significantly ( P<0.001) between the POD<24 group ( n=14) and the POD≥24 group ( n=46). Analysis showed that SUVmax > 12.8 at diagnosis, non-single nasal cavity infiltration, and response less than CR after 4–6 cycles all had a significant association with POD24. We used these data as the basis for predicting POD<24 international prognostic index (POD24-IPI). Patients were stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high risk (two or three risk factors). These groups were associated with 4-year OS rate of 100%, (85.6±9.7) %, and (65.0±10.2) %, respectively ( P=0.014). The P-GemDOx regimen was well tolerated, with hematological toxicity being the main side effect. Conclusion:This study demonstrated that the P-GemDOx regimen is effective and safe in the first-line treatment of early-stage ENKTL, and POD24-IPI is a promising prognostic model.

Objective To analyze the research hotspots and trends in the field of cancer pain drugs based on literature.Methods This article included research literature related to cancer pain and drugs published in the China National Knowledge Infrastructure(CNKI)and Web of Science databases.The visual analysis of the literature was performed by software of VOS-viewer 1.6.18 and CiteSpace 6.2.R3,including drawing the graphs and comparing the number of published articles,journals,institutions,authors and keywords were also analyzed.Results A total of 4 774 literatures were included.The journals with the largest number of articles published were the Chinese Journal of Pain Medicine and the Journal of Pain and Symptom Management.The authors with the highest number of articles published were Liu Duanqi and Bruera Eduardo.The institutions with the highest number of publications were Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,and the University of Texas Anderson Cancer Center.The most frequent keyword was cancer pain.The keywords with the strongest citation bursts included Clinical efficacy average daily cost,and primary care.Conclusion Since the beginning of the 21st century,the research on cancer pain drugs has gradually heated up,and the number of papers has shown an upward trend.From 2019 to 2022,the research on cancer pain drugs at home and abroad mainly focused on the clinical efficacy and average daily cost.This article has clarified the research hotspots of cancer pain drugs in recent years to a certain extent and has certain reference significance for future research.

Objective To investigate the effect of short-term blood glucose control on neurovascular coupling in pa-tients with diabetes mellitus type 2(T2DM).Methods The patients with T2DM who were admitted to Department of En-docrinology,The Second Affiliated Hospital of Hainan Medical University,from December 1,2021 to May 30,2023 were consecutively included in this study,and according to whether examination was performed before or after blood glucose control,they were divided into pre-blood sugar control T2DM group(T2DM-Pre-c group)and post-blood sugar control T2DM group(T2DM-Pro-c group).Healthy volunteers matched for age and sex were enrolled as healthy control(HC)group.Transcranial Doppler was used to monitor cerebral blood flow parameters,including mean blood flow velocity(Vm)of the middle cerebral artery during elbow flexion,and the T2DM group and the HC group were compared in terms of the changes in cerebral blood flow parameters after blood glucose control.Results A total of 52 T2DM patients and 36 healthy volunteers were enrolled in this study.Compared with the HC group,the T2DM-Pre-c group had significantly higher exercise-induced pulsatility index,resistance index,and time to peak of Vm(TTP-Vm)(all P<0.05).The T2DM-Pre-c group had a significantly lower Vm slope than the HC group(P=0.031).The T2DM-Pro-c group had a significant in-crease in Vm slope and a significant reduction in TTP-Vm after blood glucose control(P<0.05).Conclusion Impair-ment of neurovascular coupling is observed in patients with T2DM during the state of hyperglycemia,and short-term blood glucose control can improve neurovascular coupling.

Objective To investigate the relationship between cerebrovascular reactivity(CVR)and emotional disorders in the patients undergoing continuous hemodialysis for end-stage renal disease(ESRD).Methods The clinical data of the ESRD patients undergoing continuous hemodialysis were collected.Anxiety and depression of the patients were assessed by the Hamilton anxiety scale(HAMA)and Beck depression inven-tory,respectively.The cerebral hemodynamic changes during the breath holding test were monitored by transcrani-al Doppler sonography,and the breath-holding index(BHI)was calculated.The BHI≥0.69 and BHI＜0.69 indi-cate normal CVR and abnormal CVR,respectively.Binary Logistic regression was employed to analyze the factors affecting the depressive state of ESRD patients.Results The group with abnormal CVR exhibited higher total cholesterol level(P=0.010),low density lipoprotein level(P=0.006),and incidence of depression(P=0.012)than the group with normal CVR.Compared with the non-depression group,the depression group dis-played prolonged disease course(P=0.039),reduced body mass index(P=0.048),elevated HAMA score(P=0.001),increased incidence of anxiety(P＜0.001),decreased BHI(P=0.015),and increased incidence of abnormal CVR(P=0.012).Binary Logistic regression analysis indicated anxiety as a contributing factor(OR=22.915,95％CI=2.653-197.956,P=0.004)and abnormal CVR as a risk factor(OR=0.074,95％CI=0.008-0.730,P=0.026)for depression.Conclusion Impaired CVR could pose a risk for depression in the patients with ESRD.

Objective To investigate the differences in clinical and radiographic features between severe influenza A H1N1 and H3N2 in children.Methods The clinical and radiographic data of children diagnosed with severe influenza A H1N1 and H3N2 were analyzed retrospectively.According to the pathogen subtypes,they were divided into H1N1 group(34 cases)and H3N2 group(23 cases).Differences in clinical data,laboratory results,treatment,hospitalization time,outcome,and radiographic features between the two groups were analyzed.The t-test was used for the comparison of normally distributed measurement data between the groups,and Mann-Whitney U test was used for the comparison of non-normally distributed measurement data between the groups.Chi-square test or Fisher's exact probability method was used for the analysis of counting data,depending on the situation.Results There were differences in the season of onset,clinical and radiographic features between the two groups.H1N1 subtype mostly occurred in win-ter,and mainly manifested as respiratory symptoms(wheezing/shortness of breath)and respiratory complications(severe pneumonia).H3N2 subtype was mainly observed in summer,and more likely to involve the central nervous system(CNS),presenting with neuro-logical symptoms(convulsions),abnormal electroencephalogram,and concurrent influenza associated encephalopathy(IAE).Conclusion There are significant differences in epidemiology,clinical and radiographic features between severe influenza A H1N1 and H3N2.H3N2 has a higher probability of concurrent IAE and should be highly vigilant in clinical practice.

BACKGROUND:Sodium alginate,a natural polysaccharide,has become one of the ideal materials for preparing injectable hydrogels because it is an abundant and cheap resource,and has good biocompatibility and biodegradability.It has been widely used in the production of injectable hydrogels. OBJECTIVE:To review the properties of sodium alginate,the preparation of injectable sodium alginate hydrogel,and its application progress in tissue engineering. METHODS:Web of Science,PubMed,and CNKI were searched by computer.Chinese search terms were"sodium alginate;hydrogel;injectable",and English search terms were"alginate;hydrogel;inject".The time range of searching literature was mainly from June 2017 to June 2022. RESULTS AND CONCLUSION:Alginic acid comes from a wide range of sources,and there are many modifiable groups in its molecular structure,so many injectable hydrogels with excellent properties can be produced by various chemical crosslinking or physical crosslinking methods.Introducing other bioactive molecules or drugs into sodium alginate gel can adjust its properties and broaden its application fields.In addition,injectable sodium alginate hydrogels have great application prospects in biomedicine because of their good biocompatibility,biodegradability and other physical and chemical properties.Sodium alginate hydrogels are evenly mixed with various drugs,cells,factors or other biological molecules in vitro,and can form gels in the human body,which plays a pivotal role in gene carrier,cell scaffold and wound repair.

ObjectiveTo clarify the scientific validity of in vivo pharmacokinetic determination of the whole drug composition in Shenbai nanosuspension in rats， and to provide methodological guidance and theoretical basis for the in vivo study of multi-component complex system of traditional Chinese medicine（TCM） preparations. MethodThe concentration of the overall components， mainly total saponins and total polysaccharides in Shenbai decoction and Shenbai nanosuspension， was determined in rat plasma at different times by area under the absorbance-wavelength curve method（AUAWC）， and the concentration of individual ginsenoside Rg₁ was determined by high performance liquid chromatography（HPLC）， and the methodology was verified. The pharmacokinetic parameters of the whole component were compared with those of ginsenoside Rg₁ to evaluate the in vivo operational characteristics of the two preparations. ResultThe methodological investigations of AUAWC and HPLC were in accordance with the requirements. AUAWC analysis showed that the overall components in both the decoction group and the nanosuspension group showed a one-compartment model， with half-life（t_1/2） of 2.43 h and 2.04 h， respectively. The relative bioavailability of Shenbai nanosuspension was 138.99%. HPLC assay showed that ginsenoside Rg₁ in the decoction group and the nanosuspension group showed a two-compartment model， with distribution half-life（t_1/2α） of 0.13 h and 2.55 h， and elimination half-life（t_1/2β） were 14.28 h and 3.85 h， respectively. The relative bioavailability of Shenbai nanosuspension was 127.49%. Compared with Shenbai decoction， the time to peak（t_max）， peak concentration（C_max） and area under the drug-time curve（AUC） of the overall components and ginsenoside Rg₁ in Shenbai nanosuspension were increased. ConclusionThe established AUAWC can be used for the pharmacokinetic study of the overall components of TCM preparations， which is complementary to the results of individual components measured by HPLC， and can provide useful reference for the in vivo study of new dosage forms of TCM.

Objective:To effectively quantify and evaluate the quality of different deformation registration algorithms, in order to enhance the possibility of implementing deformation registration in clinical practice.Methods:The Jacobian determinant mean (JDM) is proposed based on the Jacobian determinant (JD) of displacement vector field (DVF), and the Jacobian determinant error (DJDE) is introduced by incorporating the JD of the inverse DVF. The optical flow method (OF-DIR) and fast demons method with elastic regularization (FD-DIR) were tested on nasopharyngeal and lung cancer datasets. Finally, JDM and DJDE with the Jacobian determinant negative percentage (JDNP), inverse consistency error (ICE) and normalized mean square error (NMSE) were used to evaluate the registration algorithms and compare the differences evaluation indicators in different tumor images and different algorithms, and the receiver operating curve (ROC) was analyzed in evaluation.Results:In lung cancer, OF-DIR outperformed FD-DIR in terms of JDM, NMSE, DJDE and ICE, and the difference was statistically significant( z = -2.24, -4.84, t = 4.01, 6.54, P<0.05). In nasopharyngeal carcinoma, DJDE, ICE and NMSE of OF-DIR were superior to FD-DIR, and the difference was statistically significant ( t = 4.46, -7.49, z = -2.22, P<0.05), but there was no significant difference in JDM ( P>0.05). In lung cancer and nasopharyngeal carcinoma, JDNP of OF-DIR was worse than that of FD-DIR, and the difference was statistically significant ( z = -4.29, -4.02, P<0.01). In addition, DJDE is more specific and sensitive on ROC curve (AUC=0.77), and has different performance result for tumor images at different sites. Conclusions:The JDM and DJDE evaluation metrics proposed are effective for deformation registration algorithms. OF-DIR is suitable for both lung cancer and nasopharyngeal carcinoma, while the influence of organ motion on the registration effect should be considered when using FD-DIR.

OBJECTIVE To provide a reference for the formulation of the antithrombotic treatment regimen of children with lower extremity deep venous thrombosis （DVT）. METHODS The clinical pharmacist participated in the antithrombotic treatment of a child with purpura nephritis complicated with lower extremity DVT and formulated an individualized dosing plan for the child. Considering that the child was readmitted to the hospital when DVT of the lower extremities did not relieve after anticoagulation therapy， it was recommended that thrombolytic therapy （Enoxaparin sodium injection 30 mg， q2 h， i.d.） be initiated after joint consultation by clinical pharmacists and physicians； catheter thrombolysis and thrombolytic drug therapy were simultaneously performed （intravenous infusion of 200 000 units of Urokinase for injection， per day）； great attention should be paid to the occurrence of adverse drug reactions in children， and the changes in coagulation indexes of the children should be monitored. For long-term anticoagulation therapy after discharge， clinical pharmacists recommended oral Rivaroxaban tablets 10 mg， qd， and adjusted the dose according to the weight change of the child. RESULTS The clinician adopted the pharmacist’s recommendations. After drug thrombolytic therapy， the child’s coagulation indicators returned to normal， the symptoms of lower extremity DVT improved significantly， and there were no adverse events of bleeding or other thrombotic events after discharge. CONCLUSIONS Clinical pharmacists can assist clinicians in formulating individualized treatment plans for children based on their expertise in pharmacy to ensure the rationality of medication use in children， which helps ensure the effectiveness and safety of medication for children.

Objective To explore the mechanism by which soybean isoflavone(SI)reduces calcium overload induced by cerebral ischemia-reperfusion(I/R).Methods Forty-eight SD rats were randomized into 4 groups to receive sham operation,cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion(I/R model group),or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+signaling pathway.Calcium levels and pathological changes in the ischemic penumbra(IP)were measured using calcium chromogenic assay and HE staining,respectively.Another 72 SD randomly allocated for sham operation,I/R modeling,or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter,and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining,and ROS level,Ca2+level,cell apoptosis,and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry;the protein expressions of Wnt5a,Frizzled-2,and P-CaMK II in the IP were detected with Western blotting and immunohistochemistry.Results In rats with cerebral I/R,Frizzled-2 knockdown significantly lowered calcium concentration(P<0.001)and the expression levels of Wnt5a,Frizzled-2,and P-CaMK II in the IP area.In soy isoflavones-pretreated rats,calcium concentration,ROS and MDA levels,cell apoptosis rate,cerebral infarct volume,and expression levels of Wnt/Ca2+signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.Conclusion Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+signaling pathway.