Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.

ObjectiveTo analyze the epidemiological and clinical characteristics of surveillance cases in a sentinel hospital for pertussis in Jiangxi Province in 2019, and to provide corresponding references for the prevention and control of pertussis. MethodsCase investigation of pertussis was conducted among sentinel hospital surveillance cases, collecting their basic information, epidemiological characteristics, clinical characteristics, and other information. ResultsA total of 125 pertussis surveillance cases were investigated in 2019, including 73 clinically diagnosed cases (58.40%) and 52 confirmed cases (41.60%). The age of onset was mainly concentrated in children under 5 years old (108 cases, 86.40%), with the largest number of cases in infants aged less than 1-year-old (48 cases, 38.40%). Most cases had a history of receiving pertussis vaccine before onset (110 cases, 88.00%), and the intervals between the onset date and the date of last dose of pertussis vaccine in the 1‒2 doses group were significantly shorter than that in the 3‒4 doses group (U=-5.990, P<0.001). Probable household transmission of pertussis was found in 3 cases. All cases had cough symptoms, mainly manifested as whooping cough (77 cases, 61.60%), in addition to other main clinical manifestations, such as fever (76 cases, 60.80%), vomiting (30 cases, 24.00%), conjunctival congestion (27 cases, 21.60%), and inspiratory whoop (16 cases, 12.80%). A total of 73 cases (58.40%) experienced complications, including 1 death case. All the cases had multiple medical visit experiences before this visit, with an interval of 2 (0,3) days between the onset date and the first visit date. The misdiagnosis rate at the first medical visit was 88.00% (110/125), and the misdiagnosis rate of the first visit in secondary and primary hospitals was significantly higher than that in tertiary hospitals, exhibiting a statistically significant difference (χ²=21.582, P<0.001). ConclusionThe clinical symptoms of pertussis cases are often atypical, and the first diagnosis is prone to misdiagnosis, so it’s necessary to further strengthen the early diagnosis capabilities for pertussis cases in healthcare institutions, especially in the primary healthcare institutions.

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Objective To investigate the expression of long non-coding RNA(lncRNA)X-inac-tive specific transcript(XIST)and microRNA-410-3p(miR-410-3p)in serum of patients with rheu-matoid arthritis(RA),and their correlation with bone mineral density(BMD)and bone metabolism indicators.Methods A total of 109 RA patients were selected as research subjects.After measuring BMD using dual-energy X-ray absorptiometry(DXA),they were divided into osteoporosis group(53 cases)and non-osteoporosis group(56 cases).BMD at different sites and serum levels of lncRNA XIST,miR-410-3p,and bone metabolism indicators[β-C-terminal telopeptide of type Ⅰ collagen(β-CTX),parathyroid hormone(PTH),osteocalcin(OC),osteoprotegerin(OPG),and N-terminal propeptide of type Ⅰ procollagen(PⅠNP)]were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between lncRNA XIST and miR-410-3p,as well as their correlation with BMD and bone metabolism indicators.Logistic regression analysis was used to screen the influencing factors for osteoporosis in RA patients.Results Compared with the non-oste-oporosis group,the osteoporosis group had lower BMD at the lumbar spine,femoral neck,greater trochanter,and Ward's triangle area,higher levels of OPG,β-CTX,and lncRNA XIST,and lower levels of mi R-410-3p,with statistically significant differences(P＜0.05).There were no statistical-ly significant differences in PTH,OC,and PⅠNP levels between the two groups(P＞0.05).Pear-son correlation analysis showed that serum lncRNA XIST levels were negatively correlated with miR-410-3p levels(r=-0.435,P＜0.001).Serum lncRNA XIST levels were negatively correlated with BMD at the lumbar spine,femoral neck,greater trochanter,and Ward's triangle area(P＜0.05),and positively correlated with OC levels(P＜0.05).Serum mniR-410-3p levels were positively correlated with BMD at the lumbar spine,femoral neck,greater trochanter,and Ward's triangle area(P＜0.05),and negatively correlated with OC levels(P＜0.05).Multivariate logistic regression analysis showed that BMD,lncRNA XIST,and miR-410-3p were all independent influencing factors for osteoporosis in RA patients(P＜0.05).Conclusion LncRNA XIST expression is upregulated in serum of RA patients with osteoporosis,while mi R-410-3p expression is downregulated.They are closely related to BMD at the lumbar spine,femoral neck,greater trochanter,and Ward's triangle area,as well as OC levels of bone metabolism indicators.

Objective:This study aimed to explore the impact of a single Scutellaria baicalensis decoction on the intestinal flora and barrier function in sepsis rats subjected to an endotoxin "second strike."Methods:Twenty-eight healthy adult male SPF-grade SD rats were utilized to develop an acute lung injury model of sepsis induced by an endotoxin "second strike." The rats were randomLy allocated into four groups: sham operation, model, normal dose Scutellaria baicalensis, and high dose Scutellaria baicalensis, with seven rats in each group. Six hours prior to model induction, the normal dose group received 2 mL of Scutellaria baicalensis decoction at 1 g/kg, while the high dose group received 4 g/kg. Both the sham operation and model groups were administered an equivalent volume of normal saline once daily for three consecutive days. Post-experiment, intestinal tissue, blood, and stool samples were collected. HE staining was used to observe intestinal histopathological changes, ELISA to detect serum D-lactic acid and Fn levels, Western blot to measure intestinal tissue NF-κB, and 16S rRNA gene sequencing to analyze intestinal flora. Correlations between intestinal flora and D-lactic acid, Fn, and NF-κB were examined.Results:Compared to the sham operation group, the model group exhibited inflammatory cell infiltration and tissue structure damage in the intestinal tissue, significantly increased NF-κB expression, markedly decreased serum Fn, and elevated D-lactic acid levels. The abundance of Firmicutes and Lactobacillus in the intestine significantly decreased, while Bacteroidota increased ( P<0.05). In contrast, the normal and high dose groups showed significantly reduced serum Fn and D-lactic acid levels, decreased intestinal NF-κB expression, and increased Firmicutes and Lactobacillus abundance ( P<0.05). Bacteroidota levels decreased, and intestinal tissue inflammatory pathology was notably alleviated. No significant differences were observed in Fn, D-lactic acid, and NF-κB expressions between the normal and high dose groups, nor in the abundance of Firmicutes, Bacteroidota, and Lactobacillus. Firmicutes abundance and the Firmicutes/Bacteroidota ratio positively correlated with Fn ( P<0.01) but negatively with D-lactic acid and NF-κB ( P<0.01). Bacteroidota abundance negatively correlated with Fn ( P<0.01) and positively with D-lactic acid and NF-κB ( P<0.01). Conclusions:Alterations in intestinal flora and mucosal barrier damage are implicated in the lung injury of sepsis rats induced by an endotoxin "second strike." Scutellaria baicalensis decoction exerts a protective effect on intestinal function in these rats, potentially by optimizing the abundance of beneficial intestinal flora, preserving the intestinal mucosal barrier, mitigating inflammatory responses, and safeguarding endothelial cell function.

Objective To investigate the clinical efficacy of Guhong Injection for the treatment of patients with coronary microvascular dysfunction(CMD)of qi stagnation and blood stasis syndrome.Methods Sixty cases of patients with CMD of qi stagnation and blood stasis syndrome who were admitted to Guangdong Provincial Hospital of Chinese Medicine from June 2021 to August 2022 were randomly divided into the control group and the trial group according to the random number table method,with 30 cases in each group.The control group was treated with conventional western medicine,and the trial group was treated with Guhong Injection on the basis of treatment for the control group.The course of treatment for the two groups covered 10 days.The changes in traditional Chinese medicine(TCM)syndrome scores,and levels of lipid indicators,serum inflammatory factors and endothelial factors in the two groups were observed before and after treatment.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)During the trial,three cases in the control group and two cases in the trial group fell off and a total of 55 cases were finally included in the statistical analysis of efficacy,including 27 cases in the control group and 28 cases in the trial group.(2)After 10 days of treatment,the total effective rate of the trial group was 89.29%(25/28),and that of the control group was 40.74%(11/27),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the trial group was significantly superior to that of the control group(P<0.01).(3)After treatment,the TCM syndrome scores of patients in both groups were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.01).(4)After treatment,the levels of lipid indicators triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)in the two groups of patients were decreased compared with those before treatment(P<0.05),and the level of high-density lipoprotein cholesterol(HDL-C)was increased compared with that before treatment(P<0.05).The intergroup comparison showed that the decrease of TG,TC,and LDL-C levels as well as the increase of HDL-C level in the trial group was significantly superior to that in the control group(P<0.05 or P<0.01).(5)After treatment,the serum levels of inflammatory factors high-sensitivity C-reactive protein(hs-CRP),interleukin 6(IL-6)and tumor necrosis factor α(TNF-α)in the two groups of patients were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.01).(6)After treatment,the serum level of endothelial factor nitric oxide(NO)in the two groups of patients was increased(P<0.05)and the serum endothelin 1(ET-1)level was decreased compared with that before treatment(P<0.05),and the increase of serum NO level,as well as the decrease of serum ET-1 level in the trial group was significantly superior to that in the control group(P<0.05 or P<0.01).Conclusion Based on the conventional treatment in western medicine,the application of Guhong Injection in the treatment of patients with CMD of qi stagnation and blood stasis syndrome exerts remarkable efficacy,which can effectively alleviate the symptoms,regulate the levels of blood lipids,reduce the inflammatory response,and improve the endothelial function.

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Tumor microenvironment(TME)is the living environment of tumor cells.The immune cells contained in TME are reprogrammed into tumor-promoting states due to various factors.Inhibiting this reprogramming effect of TME is an innovative strategy for treating tumors.As an essential factor in spindle assembly,TPX2 is considered to be a gene that promotes cancer cell proliferation and plays a role in cell response to replication stress.Highly expressed TPX2 in tumor cells promotes tumor growth through a variety of pathways,and these pathways can promote the tumor-promoting activity of immune cells in TME.Therefore,TPX2 may be a regulatory gene of TME.This paper discusses the possible mechanism of TPX2 involved in the regulation of TME by discussing the pathway medi-ated by TPX2 and the regulation of immune cells infiltrated in TME,and provides ideas for subsequent research directions.

Objective:To explore the value of chromosomal microarray analysis (CMA) in the genetic diagnosis of different types of fetal growth restriction (FGR).Methods:A retrospective analysis was conducted on 120 cases who were diagnosed with FGR by ultrasound and underwent prenatal diagnosis at the Department of Obstetrics & Gynecology and Reproductive Medicine, Peking University First Hospital, from January 2016 to December 2021. The cases were divided into three groups based on the gestational age at the first diagnosis:<28 weeks (40 cases), 28-31 +6 weeks (65 cases), and ≥32 weeks (15 cases). They were also categorized into isolated and non-isolated FGR based on the presence of other ultrasound abnormalities (69 and 51 cases in each). Chromosomal karyotype analysis and CMA were conducted on all patients. The prenatal diagnosis results were analyzed, as well as the detection of chromosomal abnormalities in different gestational age groups and types of FGR. Statistical analysis was performed using Fisher's exact test. Results:(1) A total of 14 abnormalities were detected by CMA and four cases were detected by chromosomal karyotype analysis. The abnormal detection rate of CMA was higher than that of chromosomal karyotype analysis [11.7% (14/120) vs. 3.3% (4/120), P=0.025]. Among the total 14 cases of chromosomal abnormalities, there were seven pathogenic copy number variations (CNVs) and four variants of unknown significance (VUS), as well as two cases of trisomy-18 and one case of Turner syndrome. Among the 14 cases, eight had associated ultrasound abnormalities. Eleven of the 14 cases opted for induced abortion; three continued pregnancy to delivery, with two neonates showing no abnormalities and one exhibiting slightly delayed physical development. Both methods detected three cases of aneuploidy mnumber abnormalities (2.5%, 3/120) For chromosomal abnormalities <10 Mb, the detection rate of CMA was higher than that of chromosomal karyotype analysis [9.2% (11/120) vs. 0.8% (1/120), Fisher's exact, P=0.005]. Both methods detected one case of <10 Mb CNV, while CMA alone detected ten cases of <10 Mb microdeletions/microduplications (8.3%, 10/120), including six cases of pathogenic CNVs and four cases of VUS. (2) Among the 40 cases in the <28 weeks group, six cases (15.0%) of chromosomal abnormalities were detected, including three cases of aneuploidy, two cases of pathogenic CNVs, and one case of VUS. Among the 65 cases in the 28-31 +6 weeks group, seven cases (10.8%) of chromosomal abnormalities were detected, including five cases of pathogenic CNVs and two cases of VUS. Of the 15 cases in the ≥32 weeks group, one case of chromosomal abnormality was detected, which was VUS. (3) No statistically significant difference was found in the detection rate of chromosomal abnormalities between the isolated FGR and the non-isolated FGR groups [8.7%(6/69) vs. 15.7%(8/51), Fisher's exact, P=0.263]. (4) After excluding the ≥32 weeks non-isolated FGR group (only one case), the <28 weeks non-isolated FGR group had the highest detection rate of chromosomal abnormalities (1/18), while no abnormalities were detected in the ≥32 weeks isolated FGR group. Conclusions:Among FGR fetuses, the highest detection rates of chromosomal abnormalities are found in early-onset and non-isolated FGR. Prenatal diagnosis with CMA testing can significantly improve the detection rate of genetic causes in various types of FGR fetuses.

Tumor microenvironment(TME)is the living environment of tumor cells.The immune cells contained in TME are reprogrammed into tumor-promoting states due to various factors.Inhibiting this reprogramming effect of TME is an innovative strategy for treating tumors.As an essential factor in spindle assembly,TPX2 is considered to be a gene that promotes cancer cell proliferation and plays a role in cell response to replication stress.Highly expressed TPX2 in tumor cells promotes tumor growth through a variety of pathways,and these pathways can promote the tumor-promoting activity of immune cells in TME.Therefore,TPX2 may be a regulatory gene of TME.This paper discusses the possible mechanism of TPX2 involved in the regulation of TME by discussing the pathway medi-ated by TPX2 and the regulation of immune cells infiltrated in TME,and provides ideas for subsequent research directions.