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

As the first domestically originated cell cycle protein-dependent kinase 4/6 inhibitor,dalpiciclib has been approved by the State Drug Ad-ministration for the treatment of hormone recep-tor-positive/human epidermal growth factor recep-tor 2-negative advanced or metastatic breast can-cer in combination with fulvestrant or aromatase inhibitors.This article focuses on the progress of dalpiciclib research in breast cancer,summarizing the drug's mechanism of action,phase Ⅰ-Ⅲ clinical trials,and drug safety issues.

BACKGROUND: 3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction. METHODS: In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography.The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes’ effect of promotion vaginal reconstruction and to explore the mechanism in this process. RESULTS: It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway. CONCLUSION The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway. CONCLUSION This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Objective:To investigate the safety and efficacy of MR-guided focused ultrasound surgery (MRgFUS) in treating localized prostate cancer.Methods:Six patients with localized prostate cancer who underwent MRgFUS treatment from August 2020 to September 2021 in Beijing Hospital were prospectively enrolled in this study. The patients were all over 18 years old, with an average age of (68±10) years, and had not received any prior treatment for prostate cancer. Pretreatment pelvic MR and CT scans were performed to determine the region of treatment (ROT). Different urinary catheterization measures were given based on the location of the lesion. Under general anesthesia, the lesions were treated by MRgFUS using a specialized rectal ultrasound transducer on the treatment bed. The patients were followed up at 1, 3, and 6 months after treatment and annually thereafter. During follow-up, prostate-specific antigen (PSA) levels, pelvic MR scans, International Prostate Symptom Score (IPSS), International Index of Erectile Function-15 (IIEF-15) scores, and adverse events were assessed.Results:(1) All six patients underwent MRgFUS treatment for six lesions, with an average duration of (126±56) minutes, an average number of (7.3±3.2) focal ultrasound pulses per lesion, and an average non-perfusion volume of (3.8±1.1) cm 3, which covered the entire treatment target area. No treatment-related adverse events were reported. (2) The PSA levels at baseline, 1, 3, 6, and 12 months after treatment were (6.6±0.8), (3.6±1.3), (3.4±3.0), (2.5±1.7), and (2.3±1.8) ng/ml, respectively. PSA levels increased in 2 out of 6 patients during follow-up, and pelvic MR scan revealed recurrent lesions, while PSA levels continued to decrease in the remaining 4 patients, and pelvic MR scan were normal. (3) The IPSS scores at baseline, 1, and 3 months after treatment were 13.0 (4.0, 16.0), 10.0 (4.0, 12.0), and 5.0 (3.0, 6.0) points, respectively. For the three sexually active patients, the IIEF-15 scores at baseline were 40, 51, and 14 points, respectively, and IIEF-15 at 1 month after treatment were 9, 8, and 14 points, respectively, and at 3 months after treatment were 9, 66 and 26 points, respectively. (4) One patient was diagnosed with recurrence 10 months after treatment, and another patient was found to have a new lesion 6 months after treatment. Conclusions:MRgFUS might be a safe, non-invasive, and effective treatment for localized prostate cancer, but regular follow-up is vital for detecting tumor recurrence.

Objective:To investigate perioperative management of anesthesia for septic shock.Methods:Anesthesia performed on an elderly patient with septic shock who underwent emergency surgery in Beijing Hospital was analyzed and summarized, with a literature review.Results:Etomidate, Ketamine, cis Atracurium and Remifentanil are preferred for anesthesia induction, and Remifentanil and Sevoflurane are the first choices for anesthesia maintenance.Combined application with Dexmedetomidine may improve patients' prognosis.For septic shock patients with new-onset atrial fibrillation, β-blockers are preferred for perioperative anti-arrhythmia.If necessary, propafenone or amiodarone can be used for cardioversion.Perioperative ultrasound evaluation may be used to guide perioperative fluid therapy and vasoactive drug administration for septic shock in the future.Conclusions:Anesthesiologists should place a high value on and have a good command of the main aspects of perioperative management of anesthesia for septic shock.

Objective To explore the relationship between different types of female reproductive system dysplasia and age of visit, clinical manifestations, common types of combined malformations and endometriosis. Methods The patient′s medical records in the Second Hospital of Hebei Medical University from December 2002 to June 2016 were collected and retrospectively analyzed. Results Among 924 cases of genital tract dysplasia, uterine dysplasia (65.3%, 824/1 261) was the most common, followed by vaginal dysplasia (28.3%, 357/1 261), hymen atresia and urogenital fistula (3.7%, 47/1 261), and cervical dysplasia (2.6%, 33/1 261). (1) The youngest age was in patients with hymen atresia and urogenital fistula, with a median of 14.5 years old, while the older age were in patients with uterine, vaginal and cervical dysplasia, with median age of 25.0, 24.0 and 23.0 years old, respectively. (2) The clinical manifestations were lack of specificity, mainly abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history. (3) About other systemic malformations, urological malformations were the most common (4.8%, 44/924), followed by spinal malformations (0.5%, 5/924), inguinal hernia (0.4%, 4/924), heart malformations (0.2%, 2/924), cleft lip and palate (0.2%, 2/924). Oblique vaginal septal syndrome and MRKH syndrome were the most likely to be associated with other system malformations. (4) About combination with endometriosis, there was no significant difference between obstructive genital tract malformations (2.3%, 9/385) and non obstructive genital tract malformations (1.7%, 9/539; P=0.469). Conclusions Female reproductive system dysplasia is the most common in uterine dysplasia, followed by vaginal dysplasia, hymen atresia and urogenital fistula, and cervical dysplasia. The age of visit is generally older, often found by abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history;and could be combined with a variety of other system malformations, most seen by urinary system malformations,there is also the risk of endometriosis.

Objective To estimate the prevalence and associated factors of adult female urinary incontinence in Hebei province. Methods Stratified and multistage sampling method was used, between January 2016 to May 2016, to investigate the target population in Hebei province. While, logistic regression was used to analyse datas. Results A population-based survey was conducted in 2 450 women in Hebei province, there were 2 408 effective questionnaires after deleting 48 invalid questionnaires. According to the results, the average age of subjects was (56±15) years old, and the urinary incontinence prevalence of adult female in Hebei province was 27.70%(667/2 408). Stress urinary incontinence, urge urinary incontinence and mixed urinary incontinence were diagnosed as 23.13%(557/2 408), 1.58%(38/2 408) and 2.99%(72/2 408), respectively. There were only 2.85% (19/667) urinary incontinence patients seeking medical help. The results of logistic regression analysis showed that age, daily water intake, pulmonary diseases, urinary tract infection, hypertension, chronic low back pain, dysmenorrhea, vaginitis, abortion, mode of delivery, postpartum infection were statistically significant (all P≤0.05). Among these factors, cesarean section was the protective factor for urinary incontinence (OR=0.365, 95%CI: 0.195-0.685, P<0.01). Conclusions The prevalence of urinary incontinence in adult female in Hebei province is high, and there are few patients seeking medical help. It is a common disorder in women and is associated with many factors;among these factors, cesarean section is the protective factor for urinary incontinence.

Objective To understand the status of Toxoplasma gondii infection in the population of Pu er City so as to pro-vide the evidence for formulating the strategy of toxoplasmosis control. Methods The population from Jingdong Jinggu and Menglian counties in Pu er City was surveyed IgG of T. gondii in serum was detected by ELISA. Results Totally 906 resident serum samples were detected and the IgG positive rate was 24.2%. The positive rates were higher in the aged groups of 30-39 years and 60-69 years and the difference among different aged groups was significant χ2=17.77 P 0.01 . There were no si-gnificant differences between different sexualities and among different educational levels and living habits P 0.05 . The posi-tive rates were 26.6% 194/730 15.5% 22/142 and 8.8% 3/34 in farmers students and other occupations respectively and there was a significant difference among them χ2=12.51 P 0.01 . The positive rates were 23.3% 198/849 and 36.8%21/57 in the farmers who had the habit of rearing pigs in pens and the farmers who had the habit of free ranging pigs respec-tively and there was a significant difference between them χ2=5.33 P 0.05 . Conclusion The IgG positive rate of T. go-ndii is very high in Pu er City and therefore the health education for toxoplasmosis control should be strengthened.

Objective To investigate the changing and correlation between PaCO2 and PETCO2 during laparoscopic colorectal surgery. Methods Thirty ASA Ⅰ-Ⅱ patients scheduled for laparoscopic colorectal surgery were accepted general anesthesia and trachea cannula. Hemodynamic measurements, respiratory parameters and artery blood gas analysis were drawn at 5 min after intubating, 5 min, 30 min and 60 min after pneumoperitoneum, before the side-incisions were opened and the end of operations. Results The operation time was (216.1±39.1) min, pneumoperitoneum time was (117.3±11.5) min. Comparing to the data after pneumoperitoneum, there were differences among the parameters of circulating dynamics, but the values were acceptable, pH was decreasing with time, except 5 min after pneumoperitoneum, it was significantly decreased 30 min after pneumoperitoneum until the end of operations, compared with pre-intlation value (P<0.01), pH withdrawn a little at the end of the operations. The PETCO2 and PaCO2 at different times after pneumoperitaneum were significantly higher compared with pre-inflation value (P<0.05 or<0.01). They were increasing with the time of pneumoperitoneum, and withdrawn a little at the end of the operations. There was a good correlation between PETCO2 and PaCO2, although the correlation was worst after deflation. Conclusions The circulation dynamics are stable, the correlation of PETCO2 and PaCO2 is good during the laparoscopic colorectal surgery, PaCO2 may exceed the normal value after long-term of penumoperitoneum. It is necessary to monitor the blood gas analysis during such surgeries.