Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Objective:To conduct a nationwide physician survey to better understand clinicians’ disease awareness, treatment patterns, and experience of Waldenstr?m macroglobulinemia (WM) in China.Methods:This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews.Results:The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-na?ve and relapsed/refractory patients (94% for all patients, 95% for treatment-na?ve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions:This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors’ and patients’ understanding of WM is one of the most urgent issues that must be addressed right now.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To observe the clinical effect of traditional Chinese medicine bone-setting technique using spinal,pelvi-lower extremity line to treat patients with knee osteoarthritis(KOA).Methods 426 patients with KOA were all from the First Affiliated Hospital of Hebei University of Traditional Chinese Medicine.They were randomly divided into experimental group(384 cases,57 cases of elimination,shedding and termination)by computer generated sequence.Traditional Chinese bone setting techniques were applied with spinal-pelvic-lower limb force line(divided into three parts:lumbar fixed point reduction method,hip joint push-pull and extension method and knee peripheral tendon recovery method every 3 days.2 weeks)treatment;The control group was the waiting treatment group(48 cases,6 cases were eliminated,abscission,termination),which was only used for clinical observation for 2 weeks.The main outcome index was WOMAC pain score.Secondary outcome measures were WOMAC stiffness score,functional score,standardized score and quality of life score(SF-12).The test time points were baseline,2 weeks after enrollment,and follow-up(14 weeks after enrollment).The control group was at baseline and 2 weeks after enrollment.Results Compared with baseline,WOMAC pain score,stiffness score,functional score and standardized score were all decreased in 2 groups 2 weeks after enrollment(P<0.05),but the experimental group was significantly decreased compared with the control group(P<0.001).SF-12 quality of life scores were all higher than before(P<0.001),but the experimental group was significantly higher than the control group(P<0.001).At follow-up,compared with 2 weeks after enrollment,WOMAC pain scores were increased(P<0.001),WOMAC stiffness,joint function and standardized scores were decreased(P<0.001),and SF-12 scores were increased(P<0.001).Conclusion The use of spinal-pelvi-lower extremity line of traditional Chinese medicine bone-setting technique in the treatment of KOA is effective in improving the knee joint function and improving the quality of life of patients,but the short-term effect of pain relief is good,and the long-term effect is not good.Its safety is good,and it can be considered in clinical application for KOA patients with joint dysfunction as the main manifestation.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To learn about the single nucleotide polymorphism (SNP) population structure and regional distribution characteristics of Yersinia pestis in the natural focus of plague in Qinghai-Tibet Plateau. Methods:A total of 319 representative strains of Yersinia pestis isolated from natural focus of plague in Qinghai-Tibet Plateau from 1954 to 2020 were selected, and 2 298 SNP loci included in the global Yersinia pestis phylogenetic tree were compared by whole genome sequencing technology. MEGA 6.0 software was used to construct phylogenetic trees of 319 strains of Yersinia pestis from Qinghai-Tibet Plateau, determine the SNP population structure of Yersinia pestis in the focus, and describe its regional distribution characteristics. Results:The 319 strains of Yersinia pestis isolated from Qinghai-Tibet Plateau natural plague foci were distributed in 5 clades, namely 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED. The 1.IN clade contained 209 strains (65.52%, 209/319), which was the dominant population of strains in Qinghai Province, accounting for 90.51% (143/158). The 2.ANT clade contained 83 strains (26.02%, 83/319), which was the dominant population in Tibet Autonomous Region, accounting for 67.24% (78/116). The 3.ANT, 0.PE, and 2.MED clades contained 12 (3.76%, 12/319), 9 (2.82%, 9/319) and 6 strains (1.88%, 6/319), respectively, which were scattered in Qinghai Province, Gansu Province, Sichuan Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region under the jurisdiction of Qinghai-Tibet Plateau. Conclusion:The SNP population structure of Yersinia pestis in natural focus of plague in Qinghai-Tibet Plateau is relatively rich, and the strains are distributed in 5 clades: 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED, showing the distribution characteristics of specific regions.

AIM: To understand the current status and differences in visual acuity of children of the same age from different regions of Xi'an, and to take an effective basis for the prevention of children's myopia.METHODS: Random stratified sampling was used to select the uncorrected distance visual acuity and computed dioptric data of 41 285 children aged 6-12 from 6 towns, 10 urban and rural areas and 112 country schools screened by Xi'an Central Hospital in December 2022.RESULTS: The myopia detection rate in different regions of Xi'an is 47.16% in towns, 38.59% in urban and rural areas, and 32.29% in the country, and the total myopia rate is 37.50%. The myopia rate of 6-12 years old in towns is higher than that in urban and rural areas, and that of urban and rural areas is higher than that of country; the myopia rate of girls is higher than that of boys; myopia rate increases with age; mild myopia: the myopia rate in towns is significantly higher than that of the urban and rural areas and the country; high myopia: the myopia rate in the country is significantly higher than that of the towns and the urban and rural areas. The total rate of deficient hyperopia reserves in different regions of Xi'an is 92.08% in towns, 93.67% in urban and rural areas, and 90.92% in the country, and the total rate of deficient hyperopia reserves is 92.09%. The rate of deficient hyperopia reserves at the age of 6-12 is higher in the urban and rural areas than in the towns, and higher in the towns than in the country; the total rate of deficient hyperopia reserve is higher in girls than in boys; it is the peak period of the development of hyperopia reserve rate before the age of 8.CONCLUSION: The total myopia rate and the total vision reserve deficiency rate of 6-12 years old in different regions of Xi'an are different, and 8-9 years old is the accelerated period of myopia development, and the peak of deficient hyperopia reserve is before the age of 8 years old. With the growth of age, the myopia rate shows a certain growth trend, and the rate of deficient hyperopia reserve shows a decreasing trend after reaching the peak. The total myopia rate and insufficient acuity reserve rate of girls are higher than those of boys.

Objective:To investigate the effects of gambogenic acid(GNA)on the proliferation and apoptosis of CAL27 cell xenograft tumor in nude mice.Methods:18 SPF nude mice were randomly divided into 3 groups(n=6).All nude mice were inoculated with CAL27 cells at logarithmic growth stage to establish subcutaneous transplanted tumor models.The mice in low and high dose GNA groups were treated with GNA of 8.0 mg/kg iv.and 16.0 mg/kg iv.every other day,respectively,and those in the control group was given the same amount of normal saline.The tumor growth curve was plotted during drug administration.2 weeks later,the nude mice were sacrificed,the tumor tissue was removed and the tumor inhibition rate was evaluated by the tumor size measurements.TUNEL as-say was used to detect the apoptosis of transplanted tumor cells in the groups.The expression levels of AKT,Bcl-2 and PI3K proteins in tumor tissue were detected by immunohistochemistry(IHC).The toxicity and side effects of GNA on normal tissues were detected by HE staining.Results:The transplanted tumors in low and high dose GNA groups grew slowly,and the tumor weight and volume were significantly lower than those in the control group(P＜0.05),the tumor inhibition ratio of low and high dose groups was 57.58％and 83.68％respectively.TUNEL results showed that the apoptosis index of GNA low and high dose groups was higher that of control group(P＜0.05).IHC results showed that the expression of AKT,Bcl-2 and PI3K in the tumor tissues of nude mice in low and high dose GNA groups was lower than that in the control group(P＜0.05).HE results showed that GNA had not effect on normal tissues and or-gans(P＜0.05);Conclusion:GNA may induce CAL27 cell apoptosis by regulating the expression of AKT,Bcl-2 and PI3K,and in-hibites the development of human tongue squamous cell carcinoma with little effect on normal tissues and organs.

BACKGROUND:High tibial osteotomy results in massive blood loss during the perioperative period.Tranexamic acid can effectively reduce perioperative blood loss.However,the method of tranexamic acid application has not been unified. OBJECTIVE:To investigate the effect and safety of different methods of tranexamic acid on perioperative blood loss in the high tibial osteotomy. METHODS:A total of 160 patients who underwent primary unilateral high tibial osteotomy in the Binzhou Medical University Hospital from January 2019 to December 2021,including 69 males and 91 females,were randomly divided into four groups(n=40 per group).Among them,40 patients were given an intravenous infusion of saline containing 2 g tranexamic acid 10 minutes before tourniquet release(venous group);40 patients were given an intravenous infusion of 1 g tranexamic acid and 1 g tranexamic acid was injected through a drainage tube after the closure of the incision(combined group);40 patients were given 2 g tranexamic acid infusion into drainage tube after the closure of the incision(perfusion group);an additional 40 patients were given an intravenous infusion of the same amount of normal saline(blank group).The general information was compared among the four groups of patients.The hemoglobin,hematocrit,intraoperative blood loss,drainage volume,blood transfusion rate,incision complication,and the incidence of deep vein thrombosis were recorded on days 1,3 and 5 after operation in the four groups.The total blood loss and hidden blood loss were calculated. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in general information among the four groups.(2)No significant difference was found in intraoperative blood loss among the four groups.(3)The maximum decreased values of hemoglobin and hematocrit on days 1,3 and 5 after operation,drainage volume,total blood loss and hidden blood loss were all ranked as the combined group