[Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia].

Objective: To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Methods: This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children's Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors. Results: Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×109/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively (χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant (χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively (χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%,χ2=4.13,P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%,χ2=4.06,P=0.044;(58.3±18.6)% vs. (85.7±3.2)%,χ2=9.44,P=0.002). Multivariate analysis showed that age (OR=0.58, 95%CI 0.35-0.97) and white blood cell count at first diagnosis (OR=0.43, 95%CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 (OR=0.55,95%CI 0.31-0.97), ETV6-RUNX1 fusion gene (OR=0.13,95%CI 0.03-0.54), MLL gene rearrangement (OR=2.55,95%CI 1.18-5.53) and white blood cell count at initial diagnosis (OR=0.52,95%CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions: The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

[Clinical observation of botulinum toxin A injection in the treatment of acute comitant esotropia: a retrospective cohort study].

Objective: To observe the efficacy and safety of botulinum toxin A (BTA) injection in the treatment of acute comitant esotropia (ACE) with different doses. Methods: This retrospective cohort study included data from patients with ACE who received BTA injection treatment at the First Affiliated Hospital of Zhengzhou University from June 2019 to June 2022. All patients underwent routine ophthalmic examinations, including best-corrected visual acuity (BCVA), spherical equivalent (SE), as well as specialized examinations for strabismus, including the degree of esotropia, eye movement status, and binocular visual function. Patients were categorized into small esotropia [≤60 prism diopters (PD)] and large esotropia (>60 PD) groups based on the pre-treatment degree of esotropia. Each group was further divided into 2.5 U and 5.0 U dose subgroups. Monocular injections were administered to the non-dominant eye. The esotropia degree was recorded and compared at 1, 2, 3, and 6 months of follow-up. The proportion of effectively treated patients in each group was documented. The number of cases with various levels of visual functions (including simultaneous vision, near stereopsis, and distance stereopsis) at 6 months post-treatment was compared, and complications during the follow-up period were observed. Statistical analyses were conducted using t-tests, Mann-Whitney U tests, and χ2 tests. Results: A total of 70 patients were included in the study, comprising 46 males and 24 females, with a median age of 5.0 (4.0, 8.3) years. Among them, 37 patients had small esotropia, with 25 in the 2.5 U group and 12 in the 5.0 U group. Thirty-three patients had large esotropia, with 18 in the 2.5 U group and 15 in the 5.0 U group. There were no statistically significant differences in baseline data, including age, duration of the condition, pre-treatment esotropia degree, BCVA and SE, between the two dose groups in both small and large esotropia patients (all P>0.05). In small esotropia patients, at 1 and 2 months post-treatment, the esotropia degree in the 5.0 U group was -20.00 (-37.50, -7.00) and 0.00 (0.00, 0.00) PD, respectively, which was significantly lower than the 0.00 (-10.00, 4.50) and 5.00 (0.00, 6.50) PD in the 2.5 U group (all P<0.05). At 3 and 6 months post-treatment, the esotropia degree in the 2.5 U group was 5.00 (0.00, 15.00) and 2.00 (0.00, 6.00) PD, respectively, while in the 5.0 U group, it was 0.00 (0.00, 4.50) and 0.00 (0.00, 3.75) PD, with no statistically significant differences between the two groups (all P>0.05). In the 2.5 U group, 20 cases were effectively treated, accounting for 80.0%, while in the 5.0 U group, 10 cases were effective, accounting for 10/12, with no significant difference between the two groups (P>0.05). In the 2.5 U group and the 5.0 U group, the proportions of cases with various levels of visual functions were as follows: simultaneous vision, 76.0% (19/25) and 10/12; near stereopsis, 48.0% (12/25) and 7/12; distance stereopsis, 44.0% (11/25) and 7/12, respectively. No statistically significant differences were observed in these proportions (all P>0.05). In patients with large esotropia, the esotropia degrees in the 5.0 U group at various follow-up times were -5.00 (-25.00, 5.00), 0.00 (0.00, 7.00), 2.00 (0.00, 10.00), and 5.00 (0.00, 7.00) PD, respectively. For the 2.5 U group, the corresponding values were 5.00 (2.75, 27.75), 10.00 (3.75, 24.75), 12.00 (3.75, 38.75), and 14.00 (3.50, 54.00) PD, respectively. The esotropia degrees in the 5.0 U group were consistently lower than those in the 2.5 U group (all P<0.05). The proportion of effective treatment in the 5.0 U group (13/15) was higher than that in the 2.5 U group (9/18), and the proportion of cases with distance stereopsis in the 5.0 U group (9/15) was higher than that in the 2.5 U group (4/18), both showing statistically significant differences (all P<0.05). The number of cases with simultaneous vision and near stereopsis showed no significant differences between the two groups (all P>0.05). The proportion of complications in the 2.5 U and 5.0 U groups in both large and small esotropia patients was 9/18, 13/15, 80.0% (20/25), and 10/12, respectively, with no statistically significant differences (all P>0.05). All complications spontaneously resolved within 3 months post-treatment. Conclusions: BTA injection is effective in the treatment of ACE, and for ACE patients with esotropia degrees greater than 60 PD, increasing the injection dose to 5.0 U can achieve better therapeutic outcomes.

[Efficacy and safety of intermediate-dose cytarabine in the treatment of children with refractory high risk Langerhans cell histiocytosis].

Objective: To analyze the efficacy, safety, and long-term prognosis of intermediate-dose cytarabine (Ara-c) regimen in the treatment of children with refractory risk organ involvement Langerhans cell histiocytosis (LCH). Methods: Clinical data of 17 children with multisystem and risk organ involvement LCH who failed the first-line therapy and were treated with intermediate-dose Ara-c (250 mg/m2, twice daily) regimen in the Hematology Center, Beijing Children's Hospital from January 2013 to December 2016 were analyzed retrospectively. In addition to the basic treatment of vindesine and dexamethasone, the patients received two regimens: regimen A: the intermediate-dose Ara-c combined with cladribine and regimen B: the intermediate-dose Ara-c alone. The efficacy, safety and prognosis of the two regimens were analyzed. Results: Among all 17 patients, there were 11 males and 6 females, with the diagnosis age of 2.1 (1.6, 2.7) years. Ten children received regimen A, all of them achieved active disease-better (AD-B) after 8 courses of induction therapy. The disease activity scores (DAS) decreased from 5.5 (3.0, 9.0) to 1.0 (0, 2.3). Seven children received regimen B, and 6 of them achieved AD-B after 8 courses of induction therapy. The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year overall survival rate was 100.0% in both groups, and the 5-year event free survival rate was (88.9±10.5)% and (85.7±13.2)% in group A and B. Grade 3 or 4 myelosuppression was observed in 8 patients in group A and 2 patients in group B. Conclusions: The intermediate-dose Ara-c regimen (with or without cladribine) is effective and safe for patients with refractory high-risk LCH, with a good long-term prognosis.

[Association between gestational diabetes mellitus and preterm birth subtypes].

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

[A cross-sectional study on the clinical phenotypes of rheumatoid arthritis].

OBJECTIVE: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. METHODS: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. RESULTS: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. CONCLUSION: Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.

[A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus].

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.

[Efficacy and safety of modified hemophagocytic lymphohistiocytosis 04 regimen in Beijing Children's Hospital].

Objective: To evaluate the efficacy and safety of Beijing Children's Hospital (BCH) modified hemophagocytic lymphohistiocytosis (HLH) 04 regimen in the treatment of childhood HLH. Methods: A retrospective cohort study was conducted. From January 2016 to December 2017, 110 children with HLH who were treated with the modified HLH-04 regimen (replacing dexamethasone with methylprednisolone during the induction period, reducing the dose and frequency of etoposide, and not using cyclosporine except for autoimmune-related HLH) at the Hematology Oncology Center of Beijing Children's Hospital were selected as the modified group, while 102 children treated with the standard HLH-04 regimen from January 2012 to December 2015 were selected as the control group. The early remission rate, survival rate and adverse reactions of two groups were compared. Rank sum test and chi square test were used for comparison between groups. Results: The age of onset in the modified group was 1.9 (1.1, 3.5) years, with 65 males and 45 females. The age of onset in the control group was 2.0 (1.2, 4.6) years, with 47 males and 55 females. No significant difference was found in age and gender between 2 groups (both P>0.05). Except for fibrinogen (1.3 (1.0, 1.7) vs. 1.1 (0.8, 1.4) g/L, Z=-2.67, P=0.008) and natural killer cell activity (13.9 (13.4, 16.3) % vs.14.9 (12.0, 16.1) %, Z=-2.34, P=0.028), there were no statistically significant differences in etiology, disease duration, first clinical presentation, or laboratory tests between 2 groups (all P>0.05). At 2 months and 3 years, there were no statistically significant differences in overall survival between 2 groups (84.5% (93/110) vs.76.5% (78/102), 78.2% (86/110) vs. 67.6% (69/102), χ2=2.28, 3.07, P=0.131, 0.080). The first 3 weeks were the most common time for bone marrow suppression in the modified group, with a lower incidence than in the control group (47.3% (52/110) vs. 62.7% (64/102), χ2=5.11, P=0.024). The modified group had a lower rate of fungal infections than the control group (3.6% (4/110) vs. 13.7% (14/102), χ2=6.93, P=0.008). Compared with the control group, fewer children in the modified group died as a result of side effects from chemotherapy (8.0% (2/25) vs.30.3% (10/33), χ2=4.31, P=0.038). Conclusion: The BCH modified HLH-04 regimen reduced the intensity of chemotherapy, with overall efficacy no worse than the standard HLH-04 regimen, and significantly reduced the rate of chemotherapy-related myelosuppression, fungal infection and mortality.

[Ruxolitinib combined with liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase in treatment of relapsed/refractory pediatric hemophagocytic lymphohistiocytosis].

Objective: To investigate the efficacy and safety of ruxolitinib, liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase (RU-DEP+/-L) in the treatment of relapsed/refractory (R/R) pediatric hemophagocytic lymphohistiocytosis (HLH). Methods: The clinical data of R/R pediatric HLH, who accepted the RU-DEP+/-L regimen at Beijing Children's Hospital from January 2018 to December 2019 was retrospectively analyzed. Results: A total of 16 patients were included in this study, including 13 males and 3 females, aged[M(Q1,Q3)] 1 (1, 2) years at diagnosis. Thirteen patients were diagnosed with Epstein-Barr virus (EBV)-HLH, 2 with EBV-induced primary HLH, and 1 with unclear etiology, among which 3 patients were co-infected with CMV. After the first-line treatment, 11 patients had no response, and 5 patients relapsed after complete response. Nine patients received the RU-L-DEP regimen, and 7 patients received the RU-DEP regimen. The overall response rate and complete response of RU-DEP+/-L treatment were 10/16 and 3/16, respectively. The negative conversion rate of plasma EBV-DNA was 7/15. The median follow-up time was 35.1 (2.4, 40.7) months, and 9/16 patients were survival. The 3-year overall survival rate after RU-DEP+/-L treatment in response and accepted hematopoietic stem cell transplantation (HSCT) was higher than that without response and did not receive HSCT (P=0.048). Among the 16 patients, 9 had varying degrees of myelosuppression, and 13 had an infection. Conclusions: RU-DEP+/-L can be used as a salvage treatment in R/R pediatric HLH, which can provide a bridge to HSCT and play an important role in the control of HLH. The main adverse reactions are myelosuppression and infection, which can be tolerated.

[Studies on newly recognized chronic sialadenitis].

Some kinds of chronic sialadenitis were recognized during the recent years. They have specific pathogenesis, clinical and histopathologic appearances, and require specific treatment. IgG4-related sialadenitis (IgG4-RS) is one of the immune-mediated diseases, characterized by tumefactive lesions. The incidence of IgG4-RS obviously increased during the past 30 years. The study on the potential relationship between occupational exposure to chemical substances and the incidence of IgG4-RS showed that subjects with occupational exposure to agents known to cause IgG4-RD had an increased risk for IgG4-RS. Surgical excision of involved SMG could not control the disease progression, which is not recommended for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents is effective for treating IgG4-RS, and restores salivary gland function. Radioiodine induced sialadenitis (RAIS) is one of the common complications of postoperative adjuvant treatment of differentiated thyroid cancer by 131I. The incidence of the disease is related to radiation dosage. Clinically, the patients suffered from swelling and tenderness in the buccal or submandibular regions, especially during the mealtime. Imaging appearances are similar to those of chronic obstructive sialadenitis. Conservative managements, such as gland massage, sialagogues, are the mainstream methods in the treatment of RAIS. Sialendoscopy is feasible for RAIS, but not as effective as conventional obstructive sialadenitis (COS). Therefore the prevention of RAIS is crucial. Eosinophilic sialodochitis (ES) is a new type of chronic inflammatory disease of the salivary gland related to allergy. It has characteristics of swelling of multiple major salivary glands, strip-like gelatinous plugs discharged from the duct orifice of the gland, elevated level of serum IgE and eosinophils in peripheral blood, infiltration of eosinophils and IgE positive plasma cells in the tissues, allergic history, increased expression of allergy-related cytokines, such as IL-4, IL-5, IL-13, and eotaxin, which suggest allergic reactions as a potential pathogenesis of the disease. The clinical, laboratory, histological, and immunohistochemical characteristics of ES are significantly different from conventional obstructive sialadenitis (COS). Therefore, it is suitable to separate ES from COS. Conservative managements, such as self-maintenance therapy and anti- allergic modality are the choices of treatment for ES. Based on the results of our comprehensive studies a new classification of chronic sialadenitis is suggested.

[Analysis on migration of HIV/AIDS cases and related factors in Liangshan Yi Autonomous Prefecture in Sichuan province, 2020].

Objective: To analyze the migration of the HIV/AIDS cases and related factors in Liangshan Yi autonomous prefecture (Liangshan). Methods: According to HIV/AIDS Comprehensive Response Information Management System of China Information System for Disease Control and Prevention, a total of 28 772 HIV/AIDS cases who had follow-up records in Liangshan in 2020 were included in the survey. The migration of the HIV/AIDS cases was described and the related factors were analyzed using multiple logistic regression models, and the migration destinations of the HIV/AIDS cases were mapped. Results: Among the 28 772 HIV/AIDS cases, 20.89% (6 010/28 772) had migration in 2020. Multivariate logistic regression analysis showed that among the HIV/AIDS cases, the migration related factors included being aged 15-24 years (compared with being aged 0-14 years, OR=2.74, 95%CI:2.04-3.69) and ethnic group (compared with Han ethnic group, OR=2.44, 95%CI:2.19-2.72), having education level of junior high school (compared with having education level of primary school or below, OR=1.25, 95%CI:1.14-1.38), being unmarried (compared with being married, OR=1.29, 95%CI:1.20-1.39), being engaged in business services (compared with being engaged in farming, OR=1.96, 95%CI:1.31-2.92), receiving antiviral treatment <1 year (compared with receiving antiviral treatment >3 years, OR=1.42, 95%CI:1.26-1.61), having recent CD4+T lymphocytes (CD4) counts >500 cells/µl (compared with having recent CD4 counts <200 cells/µl, OR=1.15, 95%CI:1.03-1.29). The geographical distribution maps showed that among all cities in Sichuan, Xichang (13.26%, 797/6 010) and Chengdu (10.12%,608/6 010) were the main migration destinations of the HIV/AIDS cases, and the provinces outside Sichuan where the HIV/AIDS cases would like to migrate to were mainly Guangdong (18.19%, 1 093/6 010) and Zhejiang provinces (7.67%, 461/6 010) in 2020. The HIV/AIDS cases who migrated where Liangshan, within Sichuan province, and to other provinces accounted for 27.67% (1 663/6 010), 15.34% (922/6 010) and 56.99% (3 425/6 010), respectively. Conclusions: More attention should be paid to the mobility characteristics and the classification management of HIV/AIDS cases according to their characteristics in Liangshan. Timely access to information on changes in the place of work and residence of HIV/AIDS cases should be warranted when they have migration. Good referrals and management for mobility of HIV/AIDS cases in different places should be made to reduce loss to follow-up and improving interventions.

Circular ribonucleic acid circ-FADS2 promotes colorectal cancer cell proliferation and invasion by regulating miR-498/S100A16.

The aim of this study is to examine the role and functional mechanism of circ-FADS2 in colorectal cancer (CRC). The levels of expression of circ-FADS2 were detected in 48 patients with CRC and their paired normal tissue samples and cell lines (SW480, SW620, HCT116, HT29, and NCM460) using quantitative real-time polymerase chain reaction (qRT-PCR). Circ-FADS2 was then silenced in SW480 and HT29 cells using two small interfering ribonucleic acids. Themolecular mechanism of circ-FADS2 in CRC progression and migration was then examined by sponging miR-498 and promoting S100A16 expression. After this, the expression of miR-498 and S100A16 in CRC tissues was analyzed using a qRT-PCR. In results: circ-FADS2 was found to be significantly upregulated in CRC tissues, when compared with paired normal tissues. Higher circ-FADS2 expression was associated with advanced stages, lymphatic metastasis, and reduced overall survival (OS). In addition, silencing circ-FADS2 markedly inhibited the proliferation and invasion of CRC and increased the percentage of cancer cells in the G1 phase in vitro. Reducing circ-FADS2 decreased SW480 cell proliferation in vivo. By inhibiting miR-498 expression, circ-FADS2 promoted S100A16 expression leading to the activation of the AKT pathway, resulting in CRC progression. We conclude that Circ-FADS2 expression was upregulated in CRC tissues and cells and was found to be correlated with advanced cancer, metastasis, and poor OS. A study of the molecular mechanism suggests that a circ-FADS2/miR-498/S100A16/AKT signaling cascade may be a potential therapeutic target for the treatment of CRC.

[Effectiveness and cost analysis of two chemical molluscicides in hilly schistosomiasis-endemic regions].

OBJECTIVE: To investigate the effectiveness and cost of 50% and 80% wettable powder of niclosamide ethanolamine salt (NESWP) and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in hilly schistosomiasis-endemic regions, so as to provide insights into the selection of chemical molluscicides in hilly regions. METHODS: In September 2020, a wasteland in Guanshanqiao Village, Yanrui Township, Yushan County of Jiangxi Province was selected as the experimental region, which was sectioned into five blocks and defined as four experimental groups (A1, A2, B, C) and a blank control group (D). 80% NESWP were given at doses of 1 g/m2 and 1.5 g/m2 in groups A1 and A2 using the spraying method, 50% NESWP was given at a dose of 2 g/m2 in Group B using the spraying method, and 26% MNSC was at a dose of 4 g/m2 in Group C using the spraying method, while no chemical treatment was given in Group D. Snail survey was performed using a systematic sampling method before chemical treatment and 1, 3, 7 d and 15 d post-treatment to examine the molluscicidal effect, and all molluscicidal costs were estimated to calculate the cost of chemical treatment per 1 m2 and the cost of the reduction in the mean density of living snails per 1%. RESULTS: The highest mortality of snails was 78.95% and the lowest density of living snails was 0.2388 snails/0.1 m2 in the experimental groups within 7 d of chemical treatment, and the highest mortality of snails was 94.74% and the lowest density of living snails was 0.058 0 snails/0.1 m2 7 d post-treatment. There were no significant differences in the snail mortality among the A1, A2, B and C groups 1 (χ2 = 2.250, P > 0.05), 3 (χ2 = 1.779, P > 0.05) or 15 d post-treatment (χ2 = 2.286, P > 0.05), while a significant difference was detected in the snail mortality among the four groups 7 d post-treatment (χ2 = 7.990, P = 0.046). In addition, there were no significant differences in the snail mortality between A1 and A2 groups 1 (χ2 = 0.724, P > 0.05), 3 (χ2 = 0.584, P > 0.05), 7 (χ2 = 0.400, P > 0.05) or 15 d post-treatment (χ2 = 0.251, P > 0.05). The costs of chemical treatment per 1 m2 were 0.58, 0.60, 0.64 Yuan and 0.73 Yuan in groups A1, A2, B and C, and the costs of the mean density of living snail per 1% reduction were 19.29, 20.44, 21.68 Yuan and 23.53 Yuan in groups A1, A2, B and C, respectively. CONCLUSIONS: 80% NESWP shows a high molluscicidal efficacy and low cost in hilly schistosomiasis-endemic regions.

[Association between genotype and clinical phenotype in children with primary hemophagocytic lymphohistiocytosis].

Objective: To investigate the association between genotype and clinical phenotype in children with primary hemophagocytic lymphohistiocytosis (HLH). Methods: Clinical data of 38 children with primary HLH at Beijing Children's Hospital from November 2015 to October 2020 were analyzed retrospectively. According to whether destructive mutation site, familial HLH (FHL) or non-familial HLH, degranulation pathway and non-degranulation pathway were detected in them, these patients were divided into different groups. Clinical characteristics, laboratory tests and functional tests were analyzed in different groups. Wilcoxon test or chi-square test were used for comparison between groups. Results: Among 38 cases, there were 23 males and 15 females. The age of onset was 2.5 (0.1-13.7) years. PRF1 (13/38, 34%) and UNC13D (12/38, 32%) gene mutations had the highest detectable rate. Correlation analysis between genotypes and phenotypes suggested that patients in destructive mutation sites group (n=25) had a younger age of onset than that in non-destructive mutation sites group (n=13) (1.0 (0.1-9.0) vs. 4.0 (0.4-13.4) years, Z=-2.711, P=0.005). The incidence of central nervous system involvement and convulsion was higher in patients in familial HLH group (n=26) than that in non-familial HLH group (n=12)(62% (16/26) vs. 2/12, χ²=6.631, P=0.015; 54% (14/26) vs. 2/12, χ²=4.656, P=0.040). The levels of soluble CD25, bilirubin, interferon γ (IFN-γ) and interleukin 10 (IL-10) were higher in degranulation pathway impairment group than that in the non-degranulation pathway impairment group (38 444 (2 393-44 000) vs.15 304 (1 620-36 937) ng/L,Z=2.634,P=0.008; 23.5 (6.3-126.4) vs. 6.0 (3.6-31.0) µmol/L, Z=2.992, P=0.003; 20.7 (0-248.7) vs. 11.9 (2.6-21.0) ng/L, Z=2.156, P=0.031; 20.7 (4.3-2 500.0) vs. 11.8 (4.0-88.0) ng/L, Z=2.210, P=0.027). However, the levels of neutrophils, ferritin and lactate dehydrogenase (LDH) in degranulation pathway impairment group were lower in the non-degranulation pathway impairment group (0.5 (0.1-8.0)×109 vs. 1.0 (0.9-2.3)×109/L, Z=-3.197, P=0.001; 1 133 (78-10 452) vs. 3 048 (630-37 900) µg/L, Z=-2.407, P=0.016; 410 (188-1 254) vs. 599 (389-3 147) U/L, Z=-2.489, P=0.013). Conclusions: PRF1 and UNC13D gene mutations are most common in primary HLH. Patients with destructive gene mutations have a younger age of onset. Patients with familial HLH are more likely to have central nervous system involvement and convulsions. The levels of sCD25, bilirubin, IFN-γ and IL-10 are higher in the degranulation pathway patients.

[Analysis of early recurrence within 6 months in patients of esophageal squamous cell carcinoma after neoadjuvant therapy followed by surgery].

Objectives: To examine the prognosis factors of recurrence of esophageal carcinoma within 6 months after neoadjuvant therapy followd by surgery. Methods: The clinical data of 187 patients with esophageal squamous cell carcinoma who underwent neoadjuvant therapy followed by curative esophagectomy between January 2018 and April 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital were analyzed retrospectively. There were 160 males and 27 females, aging (63.0±7.1) years (range:43 to 76 years). The t test, χ2 test and rank-sum test were used for univariate analysis of the prognosis factors for recurrence within 6 months postoperative, while the Logistic regression was used for multivariate analysis. Results: There were 30 patients (16.0%) developed recurrence within 6 months after operation, including local recurrence in 1 case, regional recurrence in 11 cases, hematogenous recurrence in 13 cases, and combined recurrence in 5 cases. Univariate analysis suggested that there was a significant difference in T staging of tumor before neoadjuvant therapy (cT), tumor regression grade, circumferential resection margin, pathological T stage (ypT) and pathological N stage (ypN) between the recurrence patients and non-recurrence patients (all P<0.05). Logistic regression analysis suggested that the cT3-4 (OR=2.701, 95%CI: 1.161 to 6.329, P=0.021) and ypN(+)(OR=1.654, 95%CI: 1.045 to 2.591, P=0.032) were the independent prognosis factors for recurrence within 6 months. Conclusion: The combination of neoadjuvant therapy and surgery is not effective in reducing early postoperative recurrence in patients who have invaded the epineurium before treatment, and still have positive lymph nodes after neoadjuvant therapy.

[Prone position thoracoscopic esophagectomy:preliminary experiences of thirty cases in Shanghai Chest Hospital].

Objective: To examine the safety and short-term outcomes of prone position thoracoscopic esophagectomy. Methods: Clinical data of consecutive thirty patients who accepted prone position thoracoscopic esophagectomy at Department of Thoracic Surgery, Shanghai Chest Hospital between July and December 2020 was analyzed retrospectively. There were 25 males and 5 females, aging 65.5(29.0) years (M(QR))(range: 48 to 82 years). Patients with cT3-4a accounted for 73.3%(22/30) and cN(+) accounted for 43.4%(18/30). All the patients in this study had no serious comorbidity, accepted prone position thoracoscopic esophagectomy. Results: No conversion to thoracotomy occurred. The overall time of operation was 210 (105) minutes (range: 130 to 268 minutes), the time of thoracic procedures was 92 (46) minutes (range: 72 to 136 minutes), the time of abdominal procedures was 32 (14) minutes (range: 20 to 48 minutes), respectively. R0 resection accounted for 93.3%(28/30), the negative ratio of circumferential margin was 96.7%(29/30). The number of lymph nodes dissection was 21.5(7.2) (range: 16.0 to 28.0) in total, 12.0(6.5) (range: 9.0 to 18.0) in thoracic lymph nodes, 2.0(1.5) (range: 1.0 to 5.0) in left recurrent laryngeal nerve lymph nodes, and 1.0(1.0) (range: 1.0 to 3.0) in right recurrent laryngeal nerve lymph nodes, respectively. There was no perioperative death, and the overall postoperative complication rate was 43.3%(13/30). The incidence of anastomotic leakage was 10.0%(3/30), recurrent laryngeal nerve paralysis was 26.7%(8/30), and respiratory complication was 6.7%(2/30). The postoperative hospital stay was 10 (9) days (range: 5 to 42 days). Conclusion: Prone position thoracoscopic esophagectomy is safe and feasible, and the short-term outcomes is satisfactory.

[Comparison of clinical and immunological features between clinically amyopathic dermatomyositis and typical dermatomyositis].

OBJECTIVE: To study the differences between clinically amyopathic dermatomyositis (CADM) and typical dermatomyositis (DM) on clinical and immunological features. METHODS: By collecting clinical data of 106 CADM patients and 158 DM patients from January 2010 to June 2019 in the department of Rheumatology and Immunology, Peking University People's Hospital, the clinical characteristics and immunological features in the two groups were compared, and the distribution characters and the clinical meanings of myositis autoantibodies were discussed in the two groups respectively. Myositis autoantibodies were measured by immunoblotting according to the manufacturers' instructions. RESULTS: In the aspects of clinical manifestations, CADM presented more with onset of interstial lung diseases (ILD) compared with DM (20.7% vs. 7.6%, P=0.002), and CADM-ILD was more likely to be acute ILD (58.3% vs. 26%, P < 0.001), and there were no differences between CADM and DM in cutaneous manifestations, accompanied with connective tissue disease (CTD) and malignancy. In CADM, the positive rate of rheumatoid factors and antinuclear antibodies was lower in DM. The most common myositis specific autoantibodies (MSAs) in CADM were anti-MDA5 (36%), anti-PL-7 (11.2%) and anti-TIF-1γ (10.1%). The most common MSAs in DM were anti-Jo-1 (19.2%), anti-TIF-1γ (11.5%) and anti-MDA5 (11.5%). Anti-MDA5 was correlated with acute ILD and skin ulceration both in CADM and DM; in CADM, skin ulceration was not associated with the titer of anti-MDA5; while in DM, skin ulceration was associated with high titer of anti-MDA5. In DM, anti-TIF-1γ was correlated with heliotrope eruption, V/shawl neck sign, perionychia erythma and malignancy, and higher rate of malignancy was seen in all titers of the anti-TIF-1γ positive patients. In CADM, anti-TIF1-γ showed no correlation with clinical manifestations. The most common myositis associated autoantibody was anti-Ro-52 both in CADM and DM. In CADM, anti-Ro-52 was associated with Raynaud's phenomenon and chronic ILD, while in DM, anti-Ro-52 was associated with mechanic's hands, noninfectious fever and accompanied CTD. CONCLUSION: Compared with DM, ILD is more likely to be acute in CADM. It is different between CADM and DM about the distribution of myositis autoantibodies and the clinical significance of the same myositis antibody, and the clinical significance of some myositis antibodies is related to titers.