This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

Objective:To investigate the effect of lappaconitine (LA) on neuropathic pain (NPP) mediated by retrograde transport of purinergic P2X3 receptor (P2X3R) in dorsal root ganglion (DRG) neurons of rats with chronic constriction injury (CCI) of the sciatic nerve.Methods:Seventy-two male healthy SD rats were selected to construct the NPP model following CCI of the sciatic nerve by ligating the right sciatic nerve. according to the random number table method. The rats were divided into CCI group, CCI+LA group and normal control group according to the random number table method, with 24 rats in each group. In normal control group, the right sciatic nerve was exposed without ligation. In CCI+LA group, the rats were given 2 g/L LA (ie, 4 mg/kg intravenously for once a day for one day only) after the same treatment as CCI group. Other two groups were injected with the identical amount of normal saline in the same way. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were evaluated before injury and at 2, 6, 12 and 24 hours after injury to evaluate the symptoms of neuralgia caused by nerve injury. The proximal and distal nerve fragments were collected in the three groups at 2, 6, 12 and 24 hours after injury. Western blotting was applied to analyze the expression of P2X3R at 2, 6, 12 and 24 hours after injury and the expression of neurotrophic factor (NGF) and tyrosine kinase receptor A (TrkA) at 24 hours after injury to evaluate the effect of LA on P2X3R, NGF and TrkA.Results:There were insignificant differences in MWT and TWL among all groups before injury (all P>0.05). Compared with normal control group, MWT and TWL were significantly decreased in CCI group and CCI+LA group at 2, 6, 12 and 24 hours after injury (all P<0.05 or 0.01). There were insignificant differences in MWT and TWL between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), while MWT and TWL were significantly higher in CCI+LA group than those in CCI group at 12 and 24 hours after injury (all P<0.05 or 0.01). In the proximal sciatic nerve segment, Western blotting showed similar levels of P2X3R among all groups at 2, 6, 12 and 24 hours after injury (all P>0.05). In the distal sciatic nerve segment, Western blotting showed higher expression of P2X3R in CCI group than that in normal control group at 2, 6, 12, 24 hours after injury (all P<0.01), higher expression of P2X3R in CCI+LA group than that in normal control group at 2, 6 and 12 hours after injury (all P<0.05), similar expression of P2X3R expression between CCI+LA group and normal control group at 24 hours after injury ( P>0.05), similar expression of P2X3R between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), and lower expression of P2X3R in CCI+LA group than that in CCI group at 12 and 24 hours after injury ( P<0.05 or 0.01). In the proximal and distal nerve fragments, the expression of NGF was lower in normal control group than that in CCI group and CCI+LA group ( P<0.05 or 0.01), but was similar between CCI group and CCI+LA group at 24 hours after injury ( P>0.05). In the proximal and distal nerve fragments, there were insignificant differences in the expression of TrkA among all groups at 24 hours after injury (all P>0.05). Conclusion:Early LA treatment after injury can alleviate mechanical and thermal hyperalgesia in NPP rats, which may be related to the reduction of P2X3R retrograde transport in DRG neuron axonal.

Objective:To establish O-(2-[ 18F]fluoroethyl)- L-tyrosine( 18F-FET) PET radiomics features-based model and investigate its predictive efficacy for isocitrate dehydrogenase type 1 (IDH1) genotyping in untreated gliomas. Methods:From November 2017 to February 2019, 58 pathologically confirmed glioma patients (36 males, 22 females; age (41.8±15.1) years) with preoperative 18F-FET PET/CT imaging in Huashan Hospital, Fudan University were retrospectively enrolled. PyRadiomics software package was used to extract 105 radiomics features. Least absolute shrinkage and selection operator (LASSO) algorithm with 5-fold cross-validation was used to build the logistic regression model. And radiomic scores (RS) of each lesion were calculated according to their weighted coefficients. The area under the receiver operating characteristic (ROC) curve was used for evaluating the predictive efficacy for IDH1 prediction. The predictive efficacies of radiomics model and traditional semi-quantitative parameters including tumor-to-background ratio (TBR; maximum TBR (TBR max), mean TBR (TBR mean), peak TBR (TBR peak)), metabolic tumor volume (MTV) and total lesion tracer uptake (TLU), were compared by Delong test. Results:Seven radiomics features including maximum 2-dimensional (2D) diameter slice, first order_maximum, first order_range, gray level co-occurrence matrix (GLCM)_joint energy, GLCM_inverse variance, gray level dependence matrix (GLDM)_dependence entropy and GLDM_large dependence low gray level emphasis were selected for the LASSO regression model building and RS calculation. ROC analysis results showed that the predictive accuracy of RS for IDH1 genotyping (mutation, n=20; wild-type, n=38) was 81.0%(47/58), with sensitivity of 65.0%(13/20), specificity of 89.5%(34/38), and area under curve (AUC) of 0.842, respectively. The traditional 18F-FET semi-quantitative parameter TLU ranked the second regarding the diagnostic performance, with accuracy of 60.3%(35/58), sensitivity of 85.0%(17/20), specificity of 47.4%(18/38), and AUC of 0.661( z=3.426, P<0.01). Conclusion:Radiomics analysis based on 18F-FET PET images can improve the predictive efficacy for IDH1 genotyping in untreated adult glioma patients.

Objective:To explore the effect of perioperative whole-course closed-loop temperature management system for prevention of hypothermia in elderly patients with femoral neck fracture.Methods:A retrospective case-control study was conducted to analyze the clinical data of 120 elderly patients with femoral neck fracture admitted to Chengdu First People's Hospital from January 2020 to December 2020. There were 48 males and 72 females, aged 60-79 years［（68.3±5.0）years］. All patients underwent total hip arthroplasty. Heat warming with the whole-course closed-loop temperature management system was applied in 40 patients（closed-loop group）, with the medical heating mattress in 40 patients（heat preservation group）, and with the quilt in 40 patients（control group）. The core body temperature of the three groups was recorded 8 minutes after wearing the temperature sensor（T0）, immediately after induction of anesthesia（T1）, 30 minutes after induction of anesthesia（T2）, 60 minutes after induction of anesthesia（T3）, at the end of surgery（T4）, and 20 minutes after entering the postanesthesia care unit（PACU）（T5）. The thrombin time（TT）, prothrombin time（PT）and activated partial thromboplastin time（APTT）were compared among groups before operation and at T4. The incidence of intraoperative hypothermia, incidence of shivering during PACU, incidence of surgical site infection, extubation time（from the day of drug withdrawal to the time of tracheal tube removal）, length of hospital stay（from the day of operation to the time of discharge）and adverse reactions related to the devices were compared among groups.Results:There was no statistically significant difference in core body temperature among three groups at T0（ P>0.05）. The core body temperature in closed-loop group［（36.61±0.28）℃］was higher than that in heat preservation group［（36.45±0.28）℃］and control group［（36.44±0.27）℃］at T1（ P<0.05）, but no statistically significant difference was found in core body temperature between heat preservation group and control group（ P>0.05）. The core body temperature in closed-loop group［（36.46±0.28）℃,（36.40±0.30）℃,（36.45±0.37）℃,（36.50±0.27）℃］was higher than that in heat preservation group［（36.32±0.31）℃,（36.24±0.26）℃,（36.28±0.30）℃,（36.24±0.31）℃］and control group［（36.12±0.30）℃,（35.98±0.28）℃,（35.73±0.31）℃,（35.81±0.32）℃］at T2-T5（ P<0.05）, and a higher temperature was found in heat preservation group than control group（ P<0.05）. The core body temperature in closed-loop group was increased at T1 compared to that at T0（ P<0.05）, while there was no statistical difference at T0 and T1 in heat preservation group and control group（ P>0.05）. The core body temperature in closed-loop group showed no significant difference at T2-T5 and T0（ P>0.05）, while the core temperature in heat preservation group and control group was decreased at T2-T5 compared to that at T0（ P<0.05）. The core body temperature in closed-loop group was within the set target temperature range. There was no statistically significant difference in TT, PT and APTT among the three groups before operation（ P>0.05）. At T4, the levels of TT, PT and APTT in closed-loop group［（18.9±1.7）seconds,（11.9±0.7）seconds,（35.5±3.3）seconds］and heat preservation group［（18.8±1.7）seconds,（11.6±0.8）seconds,（32.8±2.7）seconds］were shorter than those in control group［（20.9±1.3）seconds,（13.0±0.8）seconds,（35.7±3.4）seconds］（ P<0.05）. At T4, the levels of APTT in closed-loop group and heat preservation group were longer than those before operation（ P<0.05）. At T4, the levels of TT, PT and APTT in control group were longer than those before operation（ P<0.05）. There was no significant difference in the incidence of intraoperative hypothermia or shivering during PACU between closed-loop group［18%（7/40）, 3%（1/40）］and heat preservation group［33%（13/40）, 8%（3/40）］（ P>0.05）, which were lower than those in control group［75%（30/40）, 33%（13/40）］（ P<0.05）. There was no significant difference in the extubation time between closed-loop group［（12.5±3.6）minutes］and heat preservation group［（13.2±3.9）minutes］（ P>0.05）, which was shorter than that in control group［（16.6±4.0）minutes］（ P<0.05）. The incidence of surgical site infection and length of hospital stay were statistically insignificant among the three groups（ P>0.05）. No adverse reactions such as allergic reaction or pressure ulcers occurred in the three groups. Conclusion:For the elderly patients with femoral neck fracture, the perioperative whole-course closed-loop temperature management system can effectively maintain the core body temperature, improve coagulation function, prevent hypothermia, reduce shivering and shorten the extubation time, without increasing the risk of other adverse events, so the system can be safely used in clinical practice.

Objective:To investigate the effects and regulation mechanism of lipid-associated membrane proteins (LAMPs) derived from Mycoplasma pneumoniae( Mp) on the expression of quinine oxidoreductase 1 (NQO-1) in human monocyte cell line THP-1 cells, and to know the effect of NQO-1 to interleukin 8 secretion in LAMPs stimulated cells, so as to better understand the regulation mechanism upon Mp infection. Methods:Mp were cultivated and the precipitate was collected to extract LAMPs. The cytotoxicity of LAMPs to THP-1 cells was analyzed by using CCK8 test. THP-1 cells were cultured in vitro with different concentrations of LAMPs for different times, and the expression of NQO-1 protein was detected by Western blot. Nrf2 siRNA was used to investigate the role of Nrf2 in NQO-1 expression in LAMPs induced cells, and NQO-1 inhibitor Diminutol was performed to test whether they blocked interleukin 8 (IL-8) secretion when treated with LAMPs in THP-1 cells. Results:LAMPs extracted from Mp had no cytotoxicity to THP-1 cells. The expression of NQO-1 protein in LAMPs-stimulated THP-1 cells showed a dose-dependent and time-dependent manner. The production of NQO-1 protein reached peaks when treated with 5.0 μg/ml or 7.5 μg/ml of LAMPs for 12 h. Silencing of Nrf2 by siRNA significantly decreased NQO-1 production, and blocking NQO-1 by Dim increased the level of IL-8 in LAMPs-stimulated cells. Conclusions:LAMPs derived from Mp induced the expression of NQO-1 protein in THP-1 cells via Nrf2, and NQO-1 can inhibit IL-8 secretion in LAMPs stimulated monocytes.

Objective: To investigate the influences of antibiotic-induced gut microbiota dysbiosis on Mycoplasma pneumoniae (Mp) airway infection. Methods: C57BL/6J mice were treated with vancomycin and gentamicin for 21 d by oral delivery and then intranasally infected with Mp. Quantitative real-time PCR (qPCR) was performed to detect five major phyla of gut microbiota in mouse fecal specimens before and after antibiotic treatment and the loads of Mp in lung tissues on 3 d and 7 d after infection. Pathological changes in lung tissues were evaluated with HE staining. IFN-γ and IL-4 secreted by spleen CD4⁺ T cells and CD8⁺ T cells were analyzed by flow cytometry. Mp-specific IgM and IgG in mouse serum samples were measured by indirect enzyme-linked immunosorbent assay (ELISA). Results: Vancomycin and gentamicin treatment significantly reduced the number of Bacteroidetes in mouse feces, but increased the amount of Firmicutes. Meanwhile, the numbers of δ, γ-Proteobacteria, Actinomycetes and Tenericutes also changed. These antibiotic-induced gut microbiota alterations in mice with Mp infection increased the loads of Mp in lung tissues and the pathological scores of lung tissue inflammation on 3 d and 7 d after infection, and reduced the number of IFN-γ-secreting spleen CD4⁺ T lymphocytes on 7 d. Conclusions Antibiotic-induced gut microbiota dysbiosis aggravated Mp airway infection.

Objective:To explore the effect of acceptance and commitment therapy on self-efficacy and post-traumatic growth among young and middle-aged patients with maintenance hemodialysis.Methods:From February 2018 to February 2019, we selected patients with maintenance hemodialysis at the Second People's Hospital of Lianyungang as subjects by convenience sampling. All of patients were randomly divided into experimental group and control group with the method of random number table, 42 cases in each group. Control group carried out routine nursing. On the basis of that, experimental group implemented acceptance and commitment therapy. The effects were compared with the General Self-Efficacy Scale (GSES) and Posttraumatic Growth Inventory (PTGI) between two groups.Results:There were 41 cases finishing the research in experimental group and 42 cases in control group, except for one case of the experimental group withdrawing from the research. Six weeks after intervention, the scores of GSES and PTGI of patients in experimental group were (30.85±3.12) and (67.89±8.43) respectively higher than those in control group with statistical differences ( t=12.254, 10.002; P<0.05) . Conclusions:Acceptance and commitment therapy can improve post-traumatic growth as well as self-efficacy among young and middle-aged patients with maintenance hemodialysis.

Objective To investigate the mechanism of TNF-related apoptosis-inducing ligand (TRAIL) promoting apoptosis of pancreatic cancer cells SW1990, Patu8988 and BxPC3. Methods Three kinds of pancreatic cancer cells SW1990, Patu8988 and BxPC3 were transfected with the pCA13 plasmid carrying TRAIL gene ( pCA13 TRAIL group) and the blank plasmid control ( pCA13 group) , respectively. The expression of TRAIL mRNA in transfected cells was detected by RT-PCR, and the expression of TRAIL protein was detected by Western blot. The apoptosis rate and expression of TRAIL receptor R1 and R2 were detected by flow cytometry. Apoptosis was detected by TUNEL and Hoechst double staining, and observed by electron microscopy. The expression of caspase-3 in transfected cells was detected by immunohistochemistry. Results SW1990, Patu8988 and BxPC3 cells can expresse TRAIL mRNA and protein within 24 h after transfection. The apoptotic rate at 24 h after transfection was (27. 30 ± 5. 14)％, (13. 52 ± 0. 95)％ and (31. 40 ± 8. 70)％,respectively, which was higher than that of pCA13 group [(10. 58 ± 1. 88)％,(8. 42 ± 0. 46)％ and (16.11 ±1.66)％], respectively. The expression rates of TRAIL-R1 were (61.37 ± 3.05)％,(42.10 ± 5. 11)％ and (36. 64 ± 4. 84)％, respectively, and the expression rates of TRAIL-R2 were (36. 20 ± 4. 83)％,(37. 26 ± 8. 46)％ and (24. 32 ± 3. 71)％, respectively,which were higher than those of pCA13 group except PATU8988 cells. Positivity rates of caspase-3 were ( 14. 64 ± 5. 35 )％, ( 9. 92 ± 5. 50 )％ and (16. 12 ± 6. 74)％, which were obviously higher than ( 3. 01 ± 1. 50 )％, ( 1. 75 ± 0. 50 )％ and ( 3. 79 ± 1. 58)％ in pCA13 group,and the differences were statistically significant(P<0. 05). Conclusions TRAIL could up-regulate the expression of TRAIL R1 and R2 in multiple pancreatic cancer cell lines in vitro, and thus promote cell apoptosis.

Objective: To investigate the effects of metformin combined with clomiphene on endocrine index, vascular endothelial function, pregnancy rate and ovulation rate in infertile women with polycystic ovary syndrome(PCOS). Methods: From January 2018 to January 2019, 60 cases of PCOS with infertility treated in Zhuji People's Hospital were studied.According to the random number table, they were divided into control group and study group, with 30 cases in each group.The control group was treated with clomiphene, while the study group was treated with metformin and clomiphene.The levels of endocrine indicators including follicle stimulating hormone (FSH), luteinizing hormone (LH), pituitary prolactin (PRL), testosterone (T) and estradiol (E₂) were compared between the two groups before and after treatment.The levels of fasting insulin (FIN), fasting plasma glucose (FPG) and insulin resistance index (HOM-IR) were compared between the two groups before and after treatment.The pregnancy rate, ovulation rate and abortion rate were observed and compared between the two groups after treatment. Results: In the comparison of endocrine indicators, the levels of LH, PRL, T, E₂, FIN and FPG in the control group[(8.84±1.13)IU/L, (18.57±2.13)μg/L, (2.75±0.54)nmol/L, (62.49±5.73)ng/L, (16.55±7.84)IU/mL, (5.16±0.74)mmol/L] were improved after treatment compared with before treatment[(16.32±1.26)IU/L, (20.48±3.29)μg/L, (3.88±0.64)nmol/L, (59.13±4.95)ng/L, (21.33±5.32)IU/mL, (5.67±0.81)mmol/L; t=24.207, 2.669, 7.391, 2.431, 2.763, 2.546, P=0.000, 0.005, 0.000, 0.009, 0.004, 0.007], while the levels of FSH and HOM-IR were not significantly improved after treatment[(5.32±1.53)IU/L, (3.19±1.41)] compared with before treatment[(5.44±1.69)IU/L, (3.64±2.15); t=0.288, 0.959, P=0.387, 0.171]. The levels of LH, PRL, T, E₂, FIN, FPG and HOM-IR in the study group[(6.25±1.47)IU/L, (16.24±2.16)μg/L, (3.79±0.83)nmol/L, (68.82±4.67)ng/L, (12.69±6.24)IU/mL, (4.63±0.71)mmol/L, (2.55±1.43)] were significantly improved after treatment compared with before treatment (t=24.576, 5.437, 9.277, 6.779, 5.479, 5.621, 2.018, P=0.000, 0.000, 0.000, 0.000, 0.000, 0.000, 0.020), and the decrease of FSH was not significant after treatment[(5.17±1.55)IU/L, (5.21±1.54)IU/L]. After treatment, the levels of LH, PRL, T, FIN, FPG and HOM-IR in the study group decreased significantly, while the level of E₂ increased significantly compared with those in the control group[(6.25±1.47)IU/L, (16.24±2.16)ug/L; t=7.651, 4.207, P=0.000, 0.000]. After treatment, CIMT in both two groups[(0.075±0.018)mm, (0.067±0.016)mm]was lower than before treatment[(0.088±0.028)mm, (0.088±0.022)mm], and the improvement in the study group was better than the control group(t=1.819, P=0.037). The body mass index (BMI) and endometrial thickness of the two groups were decreased after treatment[(24.53±3.11)kg/m², (23.15±3.17)kg/m², (9.46±0.72)mm, (8.89±0.67)mm] compared with before treatment[(26.91±4.02)kg/m², (27.03±3.85)kg/m², (12.03±0.45)mm, (11.92±0.53)mm], and the improvement degree of the study group was significantly better than that of the control group(t=1.702, 3.174, P=0.047, 0.001). As to clinical outcomes, the ovulation rate and pregnancy rate of the study group (50.00%, 76.67%) were higher than those of the control group (20.00%, 50.00%)(χ²=5.034, χ²=4.593, all P<0.05), and the abortion rate of the study group (3.33%) was lower than that of the control group (13.33%), but there was no statistically significant difference (χ²=1.964, P>0.05). Conclusion Metformin combined with clomiphene can effectively improve the level of endocrine indicators, regulate insulin resistance, improve BMI, reduce endometrial thickness, correct hyperandrogenic status, effectively promote ovulation, improve pregnancy rate and achieve obvious therapeutic effect in PCOS patients with infertility.