Objective:To analyze the efficacy and safety of flumatinib,a second-generation tyrosine kinase inhibitor(TKI)independently developed in China,in patients with chronic myelogenous leukemia in chronic phase(CML-CP)who falied first-line and second-line treatment.Methods:The clinical data of 30 CML-CP patients treated with flumatinib in Lianyungang First People's Hospital from January 2020 to September 2022 were collected retrospectively.Among them,15 patients who received imatinib first-line treatment but failed treatment were included in the second-line group,and the other 15 patients who failed second-line treatment with nilotinib or dasatinib were included in the third-line group.The hematological and molecular responses of the patients in the two groups at 3,6 and 12 months of treatment,and the event-free survival(EFS)and adverse reactions of patients at the end of follow-up were statistical analyzed.Results:At 3,6,and 12 months of treatment,10,11,and 12 patients in the second line group achieved major molecular response(MMR),which was higher than that of 3,4,and 5 patients in the third line group(P=0.010,P=0.011,P=0.010).At 3 months of treatment,12 and 13 patients achieved complete hematological response(CHR)and early molecular response(EMR)in the second-line group,which was higher than that of 9 and 13 patients in the third-line group,but the difference between the two groups was not statistically significant(P=0.232,P=1.000);At 6 and 12 months of treatment,6 and 7 patients in the second-line group achieved MR4.5,which were higher than of 3 and 2 cases in the third-line group,but the difference was not statistically significant(P=0.427,P=0.713).The hematological adverse reactions of patients in the second-line group during treatment the period were mainly grade 1-2 thrombocytopenia and anemia,and no grade 3-4 of adverse reactions occurred.In the third-line group,there were 2 cases of grade 1-2 thrombocytopenia,grade 1-2 anemia and white blood cell 3 cases were reduced each,1 case of grade 3-4 anemia,2 cases of grade 3-4 neutropenia.The non-hematological adverse reactions in the second-line group were rash(2 cases),headache(1 case),diarrhea(1 case),fatigue(1 case),limb pain(1 case).There were 1 cases of diarrhea,1 cases of nausea,and 1 cases of edema in the third-line group.There was no statistical significance in hematological and non-hematological adverse reactions between the two groups of patients(P＞0.05).At the end of follow-up,the EFS rate of patients in the second-line group was higher than that in the third-line group(100％vs 93.3％),but the difference was not statistically significant(P=0.317).Conclusion:The second-generation TKI flumatinib independently developed in China,has good curative effect and safety for CML-CP patients who failed first-line and second-line treatment.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

Quantity is the key factor to ensure the safety and effectiveness of medicines. It is very important to study and determine the traditional measuring units and their quantity values of Tibetan medicine. Based on the literature records of Tibetan medicine and combined with modern experimental verification and investigation research, this study determined the reference, name, and conversion rate of traditional measuring units of Tibetan medicine. Meanwhile, through large sample sampling and repeated quantification of refe-rence of basic units, its weight and volume were clarified. The modern SI volume and weight unit values corresponding to the traditional volume and weight units of Tibetan medicine were deduced, and the correctness, reliability, and practicability of these determination results were demonstrated. This study also put forward some specific suggestions and reference values for formulating the standards of measuring units of weight and volume of Tibetan medicine. It is of great significance in guiding the processing, production, and clinical treatment of Tibetan medicine, and promoting the standardization and standardized development of Tibetan medicine.
Medicine, Tibetan Traditional ; Reproducibility of Results

Objective To investigate the populations of freshwater crabs, the intermediate host of Paragonimus and Paragonimus infections in freshwater crabs in the Minjiang River basin along the middle section of Wuyi Mountain, so as to provide baseline data for parasitic disease control and research and expansion of the parasite resource bank. Methods From November 2020 to April 2021, freshwater crabs were sampled from streams and ditches neighboring residential areas in Jianning County and its neighboring Ninghua, Shaowu, Jiangle and Shunchang counties. The crab species was identified based on the morphological features of the terminal segment of the first abdominal appendage of male crabs, and Paragonimus infections were detected in freshwater crabs. The Paragonimus metacercariae were isolated, and the types of metacercariae were identified based on the metacercaria size, cystic wall thickness, and the excretory bladder and intestinal tract morphology. In addition, the prevalence, intensity and index of metacercaria infections were calculated in freshwater crabs. Results There were seven crab species found in Jianning County and six neighboring water systems along the Minjiang River basin, including Sinopotamon jianglense, S. fukinense, Huananpotamon lichuanense, H. lini, H. shenni, H. planopodum, Bottapotamon engelhardti, and there were metacercariae of three Paragonimus species detected in these crabs, including P. westermani, P. skrjabini and P. sanpingensis, with a prevalence rate of 43.6% (125/287). The infection rates of P. westermani, P. sanpingensis and P. skrjabini were 57.1% (48/84), 26.2% (22/84) and 61.8% (21/34) in S. jianglense, and the infection rates of P. westermani and P. sanpingensis were 52.6% (51/97) and 30.9% (30/97) in S. fukinense, while the rate of P. westermani infection was 6.9% (5/72) in H. lichuanense, which is the first record of P. westermani infections in H. lichuanense. Mixed P. westermani and P. sanpingensis infections were predominantly found in freshwater crabs sampled from Jianning County, where the rate of Paragonimus infections was 70.4% (76/108), with 15.3 metacercariae identified in each crab with Paragonimus infections and 1.9 metacercariae found in each gram of crabs with Paragonimus infections, and the index of metacercariae infections was 20.5. In addition, P. westermani, P. skrjabini and P. sanpingensi metacercariae were found in freshwater crabs sampled from Jianning-neighboring counties, where the rate of Paragonimus infections was 52.3% (56/107), with 9.8 metacercariae identified in each crab with Paragonimus infections and 0.9 metacercariae found in each gram of crabs with Paragonimus infections, and the index of metacercariae infections was 4.6. Conclusion There are multiple freshwater crab species and Paragonimus infection is high in freshwater crabs in Jianning County and its neighboring Minjiang River basin, which is a high-risk natural focus for Paragonimus infections.

OBJECTIVETo evaluate the incidence rate of IDH1 in acute myeloid leukemia and analyze its effect on clinical characteristics and prognosis.

METHODSMononuclear cells in bone marrow samples were collected from 192 adult patients with newly diagnosed AML. Polymerase chain reaction (PCR) and direct sequencing were used to amplify exon 4 of IDH1 gene, the gene sequencing was used to analyze the gene mutations, at same time, the detection of NPM1, FLT3-TKD, FLT3-ITD, C-KIT, CEPBA, TET2 and JAK2V617F and MLL mutations were carried out, the follow-up was used to determine its therapeutic efficacy and outcomes of patients. The clinical and laboratory data of these cases were collected, and their clinical characteristics and prognosis were then analyzed.

RESULTSAmong the 192 AML patients, 13 cases were detected with IDH1 gene mutation, the mutation rate was 6.77% [95% CI (5.70%-13.38%)]. The sequencing chart of IDH1 gene showed double peaks, the mutations were heterozygous, out of them c.G395A (p.R132H) was found in 8 cases, c.C394T was found in 4 cases (p.R132C), c.C394A (p.R132S) was found in 1 cases, R132H and R132C are common, 13 cases showed missense mutation. The median age in mutation group was 52 years old, the median age in unnutration group was 40 years, there was significant difference between them (P = 0.010). Mutation rate of IDH1 gene in M1 and M2 was significantly higher than that in other FAB subtypes. There were no significant difference in sex, newly diagnosed peripheral white blood cell count, hemoglobin, platelet count, peripheral blood and bone marrow original cell proportion of primitive cells between them. Mutation of IDH1 gene had certain correlation with NPM1 gene mutation, but no correlation with FLT3-TKD, FLT3-ITD, C-KIT, TET2 and JAK2V617F and MLL natations was found. In addition, the IDH1 mutation easily occurred in patients with normal karyotype or in patients with middle prognostic risk karyotype, IDH1 mutation occurred in 11 cases with normal karyotype, the mutation rate was 10.28%, IDH1 mutation were observed in 2 cases with abnormal karyotype, the mutation rate was 3.50%, there was significant difference. In AML patients with middle prognostic risk karyotype. The complete remission (CR) and the 3 year survival (OS) rate of IDH1 mut patients were less than that in IDH1 wt, there was significant difference (P < 0.05).

CONCLUSIONSThe IDH1 mutation more easily occurr in older AML patients and mutations effect of IDH1 on clinical characteristics may represent a molecular marker for poor prognosis in AML.

Abnormal Karyotype ; Adult ; Exons ; Heterozygote ; Humans ; Isocitrate Dehydrogenase ; metabolism ; Leukemia, Myeloid, Acute ; enzymology ; Leukocyte Count ; Mutation ; Mutation, Missense ; Platelet Count ; Polymerase Chain Reaction ; Prognosis ; Remission Induction ; Survival Rate

Objective To evaluate the safety and tolerance of single oral dose of soxifloxacin hydrochloride in Chinese healthy subjects.Methods Seventy-two eligible subjects were randomized into 7 escalation dose groups.Eight subjects in 50 mg group were randomized to receive either study drug or placebo in the ratio of 3 to 1;each ten subjects in 100 mg, 200 mg and 300 mg group received study drug to placebo was 4∶1, respectively.Twelve subjects in 400mg and 600mg group, the ratio of study drug to placebo was 2∶1 , and ten subjects in 800 mg group was 3∶2, respectively.Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, electrocardiography and electroen-cephalogram. Results A total of 72 subjects finished study. One subject in 400 mg group had bruise on the left ankle with creatine kinase elevated, considered not related to study drug, the other one in 600 mg group complained mild dizziness and two subjects in 800 mg group complained mild nausea.All of these symptoms were assessed as related to study drug.Conclusion Soxifloxacin hydrochloride was safe and well tolerated after single oral administration at dose range of 50 to 800 mg.

OBJECTIVETo evaluate the clinical efficacy and safety of treatment of chronic primary glomerulopathy (CPG) patients of Shen deficiency and dampness heat syndrome (SDDHS) by Yishen Qingli Granule (YQG) combined with low-dose Tripterygium Wilfordii multiglycoside Tablet (TWT).

METHODSTotally 231 CPG patients of SDDHS were enrolled in this study (including 60 patients from First Affiliated Hospital of Nanjing University of Chinese Medicine, 58 from First Affiliated Hospital of Nanjing Medical University, 46 from Xinqiao Hospital of Third Military Medical University, 35 from First Affiliated Hospital of Guangzhou University of Chinese Medicine, 14 from First Affiliated Hospital of Soochow University, and 18 from Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine). They were randomly assigned to the control group (116 cases) and the trial group (115 cases) according to block group method. There were 217 cases in the safety analysis set (109 cases in the trial group vs 108 cases in the control group), and 203 cases in the full analysis set (99 cases in the trial group vs 104 cases in the control group). All patients received basic treatment such as ACEI/ARB. Furthermore, YQG (consisting of raw astragalus 10 g, prepared Polygonum Multiflorum 10 g, Pyrrosia 10 g, 1.5 g each package, containing 10 g of crude drugs) was additionally given to patients in the trial group, each package, twice daily. The TWT (10 mg) was given, twice a day. The TWT dose was adjusted according to 24 h urinary total protein (UTP). The placebos of YQG and TWT were administered to those in the control group. The treatment course consisted of 24 weeks and the follow-up visit lasted for 24 weeks. The biochemical indices were observed before and after treatment including 24 h UTP, urine red cell count (U(RBC)), renal functions (BUN, SCr), blood routine test (WBC), and liver functions (SGPT, SGOT). Reverse reactions such as gastrointestinal discomfort, skin rash, and irregular menstruation were also observed.

RESULTSCompared with the control group, the total effective rate was better in the trial group (82.83% vs 61.54%, P < 0.01). Results of stratified comparison of UTP showed better efficacy in the trial group (0.8-3.0 g/24 h, P < 0.01). The UTP decline occurred in the trial group after 8 weeks of treatment, with stable action, showing statistical difference when compared with the control group (P < 0.01). In the trial group, U(RBC) level decreased after treatment but changed more significantly. But there was no statistical difference in the changes when compared with the control group (P > 0.05). After treatment, there were no statistical difference in safety indicators such as WBC, SGPT, and SGOT between the two groups after treatment (P > 0.05).

CONCLUSIONOn the basis of basic treatment such as ACEI/ARB, application of YQG combined with low-dose TWT had better effect in controlling proteinuria of CPG patients, and could help stabilizing their conditions with less adverse reactions.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Kidney Diseases ; diagnosis ; drug therapy ; Kidney Glomerulus ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; methods ; Treatment Outcome ; Tripterygium

BACKGROUNDA multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.

METHODSAdult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.

RESULTSChanges of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.

CONCLUSIONSThe domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.

Adolescent ; Adult ; Aged ; Dialysis Solutions ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Dialysis ; methods ; Young Adult

OBJECTIVE: To compare effects of three different methods for mtDNA extraction from common sarcosaphagous insects including cetyl trimethyl ammonium bromide (CTAB) method, sodium dodecyl sulfate-potassium acetate (SDS-KAc) method and sodium dodecyl sulfate-proteinase K (SDS-PK) method. METHODS: Seventy-two insects from four species [Chrysomya megacephala (Fabricius, 1784), Eusilpha bicolor (Fairmaire, 1896), Paraeutrichopus pecoudi (Mateu, 1954), Vespa velutina (Lepeletier, 1836)] were collected from the corpses of the rabbits in Changsha district. The total DNA of above samples was extracted by CTAB, SDS-Kac and SDS-PK methods. The purity and concentration of DNA were examined by protein-nucleic acid spectrophotometry, and mtDNA were amplified by specific primers and PCR products were detected by agarose gel electrophoresis. Then PCR products were sequenced and subsequently up-loaded to GenBank. RESULTS: mtDNA was successfully extracted with three methods from most of the samples. The SDS-PK method was better in DNA purity compared to other methods and the CTAB method was superior in extracting DNA from old samples, while SDS-KAc method showed no significant difference for extraction effects of different samples. CONCLUSION The most appropriate method should be chosen depending on different situations. SDS-PK method is expected to obtain high-quality DNA, while CTAB method is preferred in extracting obsolete samples. SDS-KAc method is low cost and can be used in various kinds of preliminary experiments.
Animals ; Coleoptera/genetics* ; DNA Primers ; DNA, Mitochondrial/isolation & purification* ; Diptera/genetics* ; Electrophoresis, Agar Gel ; Entomology ; Forensic Medicine/methods* ; Gene Amplification ; Insecta/genetics* ; Polymerase Chain Reaction/methods* ; Quaternary Ammonium Compounds/chemistry* ; Rabbits ; Reproducibility of Results ; Sequence Analysis, DNA ; Sodium Dodecyl Sulfate/chemistry*

OBJECTIVETo preliminarily explore the effect of combination of volar buttress plate with external fixator for the distal radial fractures of type C3 caused by high-energy injuries.

METHODSFrom January 2001 to June 2007, 13 patients with distal radial fracture of type C3, 9 males and 4 females aged from 26 to 47 (average 37 years), were treated with volar buttress plate combined with external fixator plus the techniques of K-wires and bone grafting as necessary, whose effects were evaluated preliminarily through comparing the volar tilt, radial inclination, radial shortening and wrist function.

RESULTSFollowed up from 7 to 29 months (average 18 months), the volar tilt, radial inclination, radial shortening and wrist function of all patients recovered remarkably. Nine patients achieved excellent and 4 good according to Sarmiento score (modified by Stewart) in the radiological manifestation, while 5 patients displayed excellent, 6 good, and 2 fair according to Gartland-Werley functional assessment system.

CONCLUSION1) Volar buttress plate could support the valor cortex in order to prevent comminuted fragment from displacing and maintain volar tilt and to provide the volar fulcrum for external fixator. 2) External fixator, with the assistance of volar fulcrum, could maintain the volar tilt and the height of distal radius and help unload the fossa. 3) Supplemental K-wires fixation and the bone graft may assist fracture stable.

Adult ; Bone Plates ; External Fixators ; Female ; Fracture Fixation ; Humans ; Male ; Middle Aged ; Radius ; injuries ; surgery ; Radius Fractures ; surgery