Objective: To analyze the risk factors of recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC)，and establish a risk prediction model，so as to optimize the clinical detection and management of NMIBC. Methods: A total of 174 patients with initial diagnosis of NMIBC who underwent TURBT in the First Affiliated Hospital of Xinjiang Medical University during Jan.2020 and Oct.2022 were followed up for 24 months，and were then divided into the recurrence group (n=74) and non-recurrence group (n=100).After univariate analysis and multivariate logistic regression，risk factors of recurrence were identified，a nomogram was established，and the calibration curve was plotted，which was verified with receiver operator characteristic (ROC) curve. Results: The 2-year recurrence rate was 42.53%.Logistic regression showed high body mass index (BMI)，poor differentiation，multiple tumors，and tumor diameter greater than 3 cm were risk factors of recurrence (P<0.05，OR≥1)，while immediate postoperative intravesical instillation was a protective factor (P<0.05).The C-index of the nomogram was 0.893 (95%CI:0.851-0.938)，the area of ROC curve (AUC) was 0.894 (95%CI：0.847-0.941)，the sensitivity was 82.4%，and the specificity was 83.0%. Conclusion: The prediction model based on BMI，tumor stage，grade，number，diameter，and immediate postoperative intravesical instillation fits well and can provide reference for predicting the risk of tumor recurrence.

The concept of "Bo" （搏） originates from The Inner Canon of Yellow Emperor （《黄帝内经》）. Its original meaning mostly refers to gathering and attacking， but in pulseology it reflects the potential of conflict and was widely used in the methods of taking pulse from zang-fu organs and yin and yang. This paper conducted a literature research on the concept and connotation of "Bo" （搏）， and summarized the seven meanings of it， including contention， intersection， stop， change， attachment， pulse， and pathological pulse. At the same time， the pathomechanism of "Bo" （搏） was explained and its four characteristics are summarized， including contention to transformation， concurrent transformation， latent pathogen gathering， and changes transforming to qi； the pathomechanism and locations of "Bo" （搏） were also summarized， including zang-fu organs， channels and collaterals， five body constituents， qi level， blood level， and other aspects， involving therapeutic methods like the opening and diffusing， expressing and tonifying， regulating balance. The concept and connotation of "Bo" （搏） were systematically studied and improved to provide new perspectives and ideas for the diagnosis and treatment of many modern intractable diseases.

ObjectiveTo investigate the therapeutic effect of Dayuanyin on acute lung injury induced by H1N1 infection and decipher the potential mechanism. MethodThe constituents in Dayuanyin were analyzed by ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry （UHPLC-Q-Exactive Orbitrap MS）. Forty-eight female BALB/c mice were randomized into normal， model， oseltamivir （19.5 mg·kg^-1）， and low-， medium-， and high-dose （2.73， 5.46， 10.92 g·kg^-1） Dayuanyin groups. The normal and model groups were administrated with deionized water by gavage， and the other groups were administrated with the corresponding drugs by gavage. On day 3 of drug administration， the normal group received nasal inhalation of normal saline， and the other groups were inoculated intranasally with A/RP/8/34 （H1N1） for the modeling of influenza virus infection. Mice were administrated with drugs continuously for 7 days and weighed daily. Sampling was performed 12 h after the last administration， and the lung tissue was weighed to calculate the lung index. Hematoxylin-eosin staining was performed to observe the pathological and morphological changes of the lung tissue and bronchi. The cytometric bead array （CBA） was used to measure the serum levels of interferon-gamma （IFN-γ）， C-X-C motif ligand 1 （CXCL1）， tumor necrosis factor-alpha （TNF-α）， chemokine ligand 2 （CCL2）， interleukin-12p70 （IL-12p70）， chemokine ligand 5 （CCL5）， interleukin-1β （IL-1β）， chemokine （C-X-C motif） ligand 10 （CXCL10）， granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin-10 （IL-10）， interferon-beta （IFN-β）， interferon-alpha （IFN-α）， and interleukin-6 （IL-6）. According to the results of mass spectrometry and network pharmacology， we analyzed the mechanism of Dayuanyin in treating acute lung injury caused by H1N1. The protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， nuclear factor-kappa B （NF-κB）， and their phosphorylated forms were determined by Western blot. The mRNA levels of myeloid differentiation factor 88 （MyD88）， Toll-like receptor 3 （TLR3）， Toll-like receptor 7 （TLR7）， and Toll-like receptor 8 （TLR8） in the lung tissue were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultA total of 57 compounds， including paeoniflorin and baicalein， were detected in Dayuanyin. Compared with the normal group， the model group showed decreased body weight （P<0.01）， lung edema and hemorrhage， increased lung index （P<0.01）， and elevated levels of IFN-γ， IL-12p70， CCL5， IL-1β， CXCL10， GM-CSF， IFN-β， and IL-6 （P<0.01）. Compared with the model group， Dayuanyin attenuated alveolar wall thickening， capillary congestion， and immune cell infiltration， reduced the alterations in body weight and lung index （P<0.01）， and down-regulated the protein levels of IFN-γ， IL-12p70， CCL5， IL-1β， CXCL10， GM-CSF， IFN-β， and IL-6 （P<0.01）. A total of 57 key genes were predicted by network pharmacological analysis， of which the MAPK signaling pathway was the main target signaling pathway. Compared with the normal group， the model group showed up-regulation in the protein levels of phosphorylation （p）-ERK1/2， p-p38 MAPK， and p-NF-κB （P<0.01） and the mRNA levels of TLR7， TLR8， MyD88， and TLR3 （P<0.05， P<0.01）. Compared with the model group， Dayuanyin lowered the phosphorylation levels of ERK1/2， p38 MAPK， and NF-κB p65 in a dose-dependent manner （P<0.01） and down-regulated the mRNA levels of TLR3， TLR7， TLR8， and MyD88 （P<0.01）. ConclusionDayuanyin can prevent and control H1N1 infection-induced acute lung injury by inhibiting the TLR/MAPK/NF-κB signaling pathway.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective:To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children.Methods:In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children′s hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed.Results:Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT.Conclusion:L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.

Objective:To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH).Methods:This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children′s hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate.Results:Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive.Conclusions:For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the repair effect of electrospun gelatin polycaprolactone (GT/PCL) nanofiber aerogels (NFA) combined with cartilage extracellular matrix (ECM) for treatment of cartilage injuries in rabbits.Methods:Firstly, the GT/PCL electrospun membrane was prepared by electrospinning and was ground into the short fiber at high speed. ECM was extracted and separated from fresh bovine articular cartilage, which mixed with the short fiber solution (10 ∶1). Subsequently, it was used to prepared GT/PCL/ECM (NFA) three-dimensional scaffold. Finally, the physical characteristics of the three different scaffolds (GT/PCL, ECM and GT/PCL/ECM) were detected by scanning electron microscope and Fourier-transform infrared (FTIR) spectrometer, including the composition, microstructure, swelling rate, porosity, compressive strength and degradation rates. And the biocompatibility research was getting on by co-culturing the scaffold with chondrocytes. Fifteen male New Zealand white rabbits were divided into blank control group (Group A, n=5), ECM group (group B, n=5) and composite scaffold(GT/PCL/ECM)group (Group C, n=5) according to the random number table. An injury model was established and three types of bio-scaffold materials were implanted into different groups. At 3 weeks, the cartilage repair was evaluated among groups by semi quantitative global MRI scoring system (WORMS). After the animals were killed, the knee joints of each group were scored by the international society for cartilage repair histological score (ICRs); the ICRs histological score was performedby HE staining and safranine green staining. Results:Three scaffolds showed a porous three-dimensional structure under the scanning electron microscope. FIRT showed that GT and PCL were introduced into the scaffolds successfully. The GT/PCL NAF was loose and unable to be characterized by materials science. The swelling rate of GT/PCL/ECM scaffold [(1, 092.0±32.2)%] was higher than that of ECM scaffold [(933.6±16.3)%] ( P<0.01). The porosity of GT/PCL/ECM scaffold [(92.3±2.3)%] was higher than that of ECM scaffold [(85.9±2.2)%] ( P<0.05). The compressive strength of ECM scaffold [(2.7±0.1)kPa] and of GT/PCL/ECM scaffold [(2.4±0.1)kPa] showed no statistical difference ( P>0.05). The degradation rate of ECM scaffold was higher than that of GT/PCL/ECM scaffold, but the difference was not statistically significant ( P>0.05). The cytotoxicity rating of GT/PCL/ECM scaffold was grade I, indicating that its biocompatibility was better. At 3 weeks, the MRI WORMS score in Group C [(49.0±11.4)points] was significantly higher than that in Group B [(40.0±6.7)points] and that in Group A [(24.0±6.5) points] ( P<0.05 or 0.01); the general ICRS score of group C was [(7.4±1.1) points], which was significantly higher than that of group B [(4.6±1.1)points] and group A [(3.0±1.2)points] ( P<0.01); The ICRS histological scores of group C and group B were [(6.8±0.8)points] and [(4.2±0.8)points] respectively compared with group A [(2.8±0.8)points] were significantly higher ( P<0.05 or 0.01). Conclusion:GT/PCL/ECM (NFA) scaffold has similar tissue structure to natural cartilage and is superior to traditional ECM scaffold in physical properties and biocompatibility, which provides a stable environment for chondrocyte adhesion and growth, promotes collagen regeneration, and thus accelerates the repair of cartilage injury.

Objective:To understand the clinical characteristics and prognosis of Langerhans cell histiocytosis (LCH) with skin-limited lesion.Methods:A retrospective analysis was performed on clinical characteristics and prognosis of 16 skin-limited LCH patients, out of 578 LCH patients who were hospitalized in Beijing Children′s Hospital during December 2013 to June 2018.Results:A total of 16 skin-limited LCH cases, accounted for 2.7% of all 578 cases, were included.Among which, sex ratio (male vs.female) was 1.28∶1.00.Median ages of skin eruption occurrence and of diagnosis of the disease were 3.5 months (3 days to 2 years and 5 months) and 6 months (2 months 14 days to 2 years and 8 months) in this group.Among the 16 cases, seborrheic dermatitis-like lesions(11 cases, 68.7%) was the most common, and the trunk was most frequently involved[75.0% (12 cases)]. Serine/threonine protein kinase gene V600E [ BRAF (p.V600E)] mutation was detected in pathological specimens from 10 skin-limi-ted cases, with 9 cases being positive.Plasma samples from 5 positive cases were further detected for BRAF (p.V600E) mutation, and 4 positive results were gained.Of all 16 patients, 11 cases (68.7%) were treated.Remission were achieved in 3-6 months from treatment start in patients treated whether according to the Histiocyte Society′s LCH-2009 protocol for 25 weeks(6 cases, 37.5%), or with topical mometasonefuroate for 3 months (3 cases, 18.8%). Two patients(12.5%) with solitary cutaneous lesions underwent excision biopsy (one face and one prepuce) and were considered to be in remission immediately after surgery.None of these patients suffered from the recurrence of the disease.The remaining 5 patients (31.3%) with skin-limited LCH were just evaluated regularly, and achieved remission in 3-6 months of commencing observation.Among these untreated patients, 1 with consistently positive BRAF (p.V600E) mutation in plasma had bone involvement in the 24 th month of assessment, and was then treated based on the Histiocyte Society′s LCH-2009 Protocol.No clinical or imageological evidence supporting disease progression was found on this patient.Median follow-up period was 32.8 months (2.9-63.9 months). Except one patient, none of the rest cases had active disease till follow-up ended.Two-year event free survival(EFS) of this research was (92.3± 7.4)%.There was no significant difference between EFS of treated group and that of observation group( χ2=1.250, P=0.264). Conclusions:Skin-limited LCH often occurs in infants and newborns, with strong heterogeneity in clinical manifestations, laboratory indicators, and pathogenesis.Seborrheic dermatitis-like lesions were the most common cutaneous type.The prognosis of the patients is excellent despite progressing into multisystem involvement can be seen in a few patients.

Objective:To evaluate the prognostic value of Epstein-Barr virus (EBV)-DNA level in plasma and whole blood in treatment of children with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH).Methods:Clinical data of 66 children with EBV-HLH, who were admitted to the Hematology and Oncology Center of Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2017 were retrospectively reviewed and analyzed.The data included the dynamic changes of the EBV-DNA level in plasma (P-EBV-DNA) and whole blood (W-EBV-DNA) at the time of admission, 2 and 4 weeks after treatment.P-EBV-DNA was divided into the positive group and the negative group according to the copy number of EBV-DNA, and W-EBV-DNA was divided into the high and the low level group by the receiver operating characteristic curve(ROC); the incidence of poor prognosis was compared between different groups by Chi- Square test; the event-free survival (EFS)was evaluated by the Log- Rank test to identify its prognostic significance. Results:The analysis showed that both P-EBV-DNA and W-EBV-DNA at admission could not be associated with a poor outcome; P-EBV-DNA (≥500 copies/mL) or W-EBV-DNA [>(5.04-5.09)×10 5 copies/mL]after 2 and 4 weeks of treatment could be a good marker of a poor outcome and progression-free survival ( P<0.001). Besides, central nervous system (CNS) involvement ( P=0.025), sever leukopenia(WBC≤3×10 9/L, P=0.031), neutropenia (ANC ≤0.5×10 9/L, P=0.041), albumin reduction (≤26 g/L, P=0.012) and hemoglobin decrease (≤90 g/L, P=0.023) at diagnosis are also associa-ted with worse outcomes.In multivariate analysis, only P-EBV-DNA at 4 th week and CNS involvement were indepen-dent prognostic factors ( HR=7.139, P=0.032 and HR=6.455, P=0.042, respectively). The prognostic value of W-EBV-DNA at different time points and P-EBV-DNA after 2 weeks of treatment had a lower prognostic value. Conclusions:The P-EBV-DNA level after 4 weeks of treatment is a promising risk indicator for early diagnosis of disease and early recognition of poor prognosis in EBV-HLH children, so it provides the guidance for optimal treatment.