The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

Objective:This study aims to investigate the determinants influencing the efficacy of microsurgical sperm retrieval in individuals diagnosed with idiopathic non-obstructive azoospermia (iNOA).Methods:A retrospective analysis was performed on the clinical data of 757 patients diagnosed with iNOA who underwent microsurgical sperm extraction at Peking University Third Hospital between January 2019 and December 2021. The median age of patients was 31(29, 33)years, and the duration of infertility was 3(2, 5)years. A total of 169 patients (22.3%) received preoperative pharmacological treatment with agents such as follicle-stimulating hormone, human chorionic gonadotropin, or aromatase inhibitors. Additionally, 327 patients (43.2%) underwent testicular biopsy (TESA) prior to surgery. Among these, 51 cases (15.9%) exhibited sperm presence on smear microscopy, while 57 cases (17.8%) demonstrated sperm presence on pathological examination. The pathological classifications of the biopsies included 102 cases (31.9%) of reduced spermatogenic function, 66 cases (20.6%) of delayed sperm maturation, and 63 cases (19.7%) of sertoli cell-only syndrome.Preoperative median pituitary prolactin(PRL)was 9.1(6.5, 12.5)ng/ml, follicle-stimulating hormone (FSH)20.1(14.2, 28.5)U/L, luteinizing hormone (LH)7.9(5.5, 11.3)U/L, testosterone(T)117 .0(81.3, 154.0)nmol/L, estradiol(E2)8.7(6.3, 11.8)pmol/L. Under general anesthesia, patients underwent microsurgical testicular incision for sperm retrieval.The surgical testicular volume was measured at a median of 6(5, 10) ml. Among the cases studied, 59 patients (7.7%) underwent left testicular surgery, 213 patients (28.1%) underwent right testicular surgery, and 485 patients (64.0%) underwent bilateral testicular surgery. Furthermore, 44 patients (5.8%) underwent a second microsurgical sperm retrieval procedure, while 4 patients (0.5%) underwent a third procedure.Based on the presence of sperm identified during the surgical procedure, participants were categorized into a sperm retrieval group and a non-sperm retrieval group. Clinical data of these two groups were analyzed. A subgroup analysis was performed on the observed indicators. Both univariate and multivariate logistic regression analyses were employed to examine the factors influencing the micro sperm retrieval rate.Results:Among the 757 iNOA patients, 255(33.7%) obtained sperm through micro sperm retrieval, while 502(66.3%) did not obtain sperm through micro sperm retrieval. The age of sperm-receiving group was higher than that of the non-sperm-receiving group [32(30, 35)years vs. 30(28, 33)years, P<0.01], and the course of infertility was longer than that of the non-sperm-receiving group [3.0(2.0, 5.5)years vs. 3.0(2.0, 4.0)years, P=0.004]. There was no significant difference in the sperm acquisition rate in the subgroup with or without preoperative drug treatment [38.5%(65/169)vs. 32.7%(185/566), P=0.164]. There was statistical significance in the sperm collection rate of different TESA results in subgroups [85.7%(24/28)of sperm were detected by microscopic smear and pathological examination and 75.9%(22/29)of sperm were detected by pathological examination and no sperm were detected by microscopic smear and 17% of sperm were not detected by microscopic smear and pathological examination (42/247), P<0.01). The rate of spermatogenesis in the subgroup with low spermatogenic function was significantly higher than that in the subgroup with spermatogenic maturation retardation and sercell-only syndrome [47.1%(48/112), 12.1%(8/66)vs. 11.1%(7/63), P<0.01]. There was no significant difference in testicular volume between the seminal and non-seminal groups [6.0(5.0, 10.0)ml vs. 6.0(5.0, 9.5)ml, P=0.862]. Pituitary prolactin [8.3(5.8, 12.0)ng/ml vs. 9.3(7.5, 13.0)ng/ml, P=0.001] and FSH[18.3(11.8, 27.4)U/L vs. 20.7(15.2, 28.7)U/L, P=0.005] in spermated group were lower than those in non-spermated group. Luteinizing hormone [7.6(5.1, 11.0)U/L vs. 8.0(5.6, 11.5)U/L, P=0.126], testosterone [8.8(6.0, 11.8)nmol/L vs. 8.7(6.4, 11.7)nmol/L, P=0.607], estradiol [124.0(87.8, 156.0)nmol/L vs. 114.5(79.9, 151.3)nmol/L, P=0.105] had no significant difference. The recovery rate of the first operation was higher than that of the second operation [97.7%(43/44)vs. 81.8%(36/42), P=0.032]. The sperm retrieval rate of bilateral operation was significantly lower than that of unilateral operation [6.0% bilateral (29/485)vs. 86.4% left (51/59)vs. 82.2% right (175/213), P<0.01]. The proportion of no sperm on one side of bilateral operation and only 4.7%(23/485)on the opposite side were obtained. The results of multivariate analysis showed that >30 and ≤40 years old subgroup ( OR=2.226, 95% CI 1.364-3.632, P=0.001), >40 and ≤50 years old subgroup ( OR=4.282, 95% CI 1.457-12.588, P=0.008)was higher than that of >20 and ≤30 years old subgroup. The sperm acquisition rate of the sperm subgroup was significantly increased by smear microscopy and pathological examination ( OR=6.486, 95% Cl 1.444-29.127, P=0.015), while the sperm acquisition rate of the sperm subgroup was not significantly decreased by smear microscopy and pathological examination ( OR=0.420, 95% Cl 0.200-0.881, P=0.022). The pathological type of puncture was associated with lower spermatogenesis maturation block ( OR=0.099, 95% CI 0.019-0.509, P=0.006). Higher FSH (>7.6 U/L)was associated with lower sperm yield ( OR=0.324, 95% CI 0.122-0.856, P=0.023). Conclusions:Age, FSH level, results of testicular biopsy and pathologic type of biopsy are independent factors affecting the sperm retrieval rate of iNOA patients undergoing micro-TESE. The success rate of sperm retrieval diminished following multiple surgical procedures. Furthermore, for patients who did not have sperm successfully retrieved from one side, that the likelihood of sperm retrieval from contralateral surgery would also be low.

Objective:This study aims to investigate the determinants influencing the efficacy of microsurgical sperm retrieval in individuals diagnosed with idiopathic non-obstructive azoospermia (iNOA).Methods:A retrospective analysis was performed on the clinical data of 757 patients diagnosed with iNOA who underwent microsurgical sperm extraction at Peking University Third Hospital between January 2019 and December 2021. The median age of patients was 31(29, 33)years, and the duration of infertility was 3(2, 5)years. A total of 169 patients (22.3%) received preoperative pharmacological treatment with agents such as follicle-stimulating hormone, human chorionic gonadotropin, or aromatase inhibitors. Additionally, 327 patients (43.2%) underwent testicular biopsy (TESA) prior to surgery. Among these, 51 cases (15.9%) exhibited sperm presence on smear microscopy, while 57 cases (17.8%) demonstrated sperm presence on pathological examination. The pathological classifications of the biopsies included 102 cases (31.9%) of reduced spermatogenic function, 66 cases (20.6%) of delayed sperm maturation, and 63 cases (19.7%) of sertoli cell-only syndrome.Preoperative median pituitary prolactin(PRL)was 9.1(6.5, 12.5)ng/ml, follicle-stimulating hormone (FSH)20.1(14.2, 28.5)U/L, luteinizing hormone (LH)7.9(5.5, 11.3)U/L, testosterone(T)117 .0(81.3, 154.0)nmol/L, estradiol(E2)8.7(6.3, 11.8)pmol/L. Under general anesthesia, patients underwent microsurgical testicular incision for sperm retrieval.The surgical testicular volume was measured at a median of 6(5, 10) ml. Among the cases studied, 59 patients (7.7%) underwent left testicular surgery, 213 patients (28.1%) underwent right testicular surgery, and 485 patients (64.0%) underwent bilateral testicular surgery. Furthermore, 44 patients (5.8%) underwent a second microsurgical sperm retrieval procedure, while 4 patients (0.5%) underwent a third procedure.Based on the presence of sperm identified during the surgical procedure, participants were categorized into a sperm retrieval group and a non-sperm retrieval group. Clinical data of these two groups were analyzed. A subgroup analysis was performed on the observed indicators. Both univariate and multivariate logistic regression analyses were employed to examine the factors influencing the micro sperm retrieval rate.Results:Among the 757 iNOA patients, 255(33.7%) obtained sperm through micro sperm retrieval, while 502(66.3%) did not obtain sperm through micro sperm retrieval. The age of sperm-receiving group was higher than that of the non-sperm-receiving group [32(30, 35)years vs. 30(28, 33)years, P<0.01], and the course of infertility was longer than that of the non-sperm-receiving group [3.0(2.0, 5.5)years vs. 3.0(2.0, 4.0)years, P=0.004]. There was no significant difference in the sperm acquisition rate in the subgroup with or without preoperative drug treatment [38.5%(65/169)vs. 32.7%(185/566), P=0.164]. There was statistical significance in the sperm collection rate of different TESA results in subgroups [85.7%(24/28)of sperm were detected by microscopic smear and pathological examination and 75.9%(22/29)of sperm were detected by pathological examination and no sperm were detected by microscopic smear and 17% of sperm were not detected by microscopic smear and pathological examination (42/247), P<0.01). The rate of spermatogenesis in the subgroup with low spermatogenic function was significantly higher than that in the subgroup with spermatogenic maturation retardation and sercell-only syndrome [47.1%(48/112), 12.1%(8/66)vs. 11.1%(7/63), P<0.01]. There was no significant difference in testicular volume between the seminal and non-seminal groups [6.0(5.0, 10.0)ml vs. 6.0(5.0, 9.5)ml, P=0.862]. Pituitary prolactin [8.3(5.8, 12.0)ng/ml vs. 9.3(7.5, 13.0)ng/ml, P=0.001] and FSH[18.3(11.8, 27.4)U/L vs. 20.7(15.2, 28.7)U/L, P=0.005] in spermated group were lower than those in non-spermated group. Luteinizing hormone [7.6(5.1, 11.0)U/L vs. 8.0(5.6, 11.5)U/L, P=0.126], testosterone [8.8(6.0, 11.8)nmol/L vs. 8.7(6.4, 11.7)nmol/L, P=0.607], estradiol [124.0(87.8, 156.0)nmol/L vs. 114.5(79.9, 151.3)nmol/L, P=0.105] had no significant difference. The recovery rate of the first operation was higher than that of the second operation [97.7%(43/44)vs. 81.8%(36/42), P=0.032]. The sperm retrieval rate of bilateral operation was significantly lower than that of unilateral operation [6.0% bilateral (29/485)vs. 86.4% left (51/59)vs. 82.2% right (175/213), P<0.01]. The proportion of no sperm on one side of bilateral operation and only 4.7%(23/485)on the opposite side were obtained. The results of multivariate analysis showed that >30 and ≤40 years old subgroup ( OR=2.226, 95% CI 1.364-3.632, P=0.001), >40 and ≤50 years old subgroup ( OR=4.282, 95% CI 1.457-12.588, P=0.008)was higher than that of >20 and ≤30 years old subgroup. The sperm acquisition rate of the sperm subgroup was significantly increased by smear microscopy and pathological examination ( OR=6.486, 95% Cl 1.444-29.127, P=0.015), while the sperm acquisition rate of the sperm subgroup was not significantly decreased by smear microscopy and pathological examination ( OR=0.420, 95% Cl 0.200-0.881, P=0.022). The pathological type of puncture was associated with lower spermatogenesis maturation block ( OR=0.099, 95% CI 0.019-0.509, P=0.006). Higher FSH (>7.6 U/L)was associated with lower sperm yield ( OR=0.324, 95% CI 0.122-0.856, P=0.023). Conclusions:Age, FSH level, results of testicular biopsy and pathologic type of biopsy are independent factors affecting the sperm retrieval rate of iNOA patients undergoing micro-TESE. The success rate of sperm retrieval diminished following multiple surgical procedures. Furthermore, for patients who did not have sperm successfully retrieved from one side, that the likelihood of sperm retrieval from contralateral surgery would also be low.

Objective:To observe the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating apoptosis during malignant transformation of human bronchial epithelial cells (HBE cells) induced by sodium arsenite (NaAsO 2). Methods:HBE cells were treated with 0.0 and 1.0 μmol/L NaAsO 2, which were control group and arsenic exposed group respectively. HBE cells were treated with 1.0 μmol/L NaAsO 2 for 43 passages to establish a malignant transformation model. The dynamic changes of indexes in different passages (0, 1st, 8th, 15th, 22nd, 29th, 36th, and 43rd) after exposure to NaAsO 2 were monitored, including the apoptosis rate detected by flow cytometry and apoptosis-related proteins and Nrf2 protein detected by Western blotting. Nrf2 siRNA was transfected into malignant transformed HBE cells (T-HBE cells) to silence Nrf2. The silencing effect of Nrf2 protein was verified. And, the apoptosis rate and apoptosis-related proteins were detected. Results:With the increase of arsenic exposure, the apoptosis rates of HBE cells decreased (0, 1, 8, 15, 22, 29, 36 and 43 passages were 0.370 ± 0.029, 0.443 ± 0.069, 0.357 ± 0.046, 0.330 ± 0.016, 0.273 ± 0.050, 0.160 ± 0.024, 0.110 ± 0.022, 0.097 ± 0.012, respectively, Ftrend = 22.981, P < 0.05). Compared with the 0 passage cells, the apoptosis rates of the 22nd, 29th, 36th and 43rd passages in the arsenite group were lower. The differences between them were statistically significant ( P < 0.05). With the increase of arsenic exposure, the expressions of pro-apoptotic proteins caspase-3, cleaved-caspase-3, C/EBP-homologous protein (CHOP) and B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) showed downward trends ( Ftrend = 22.356, 3.738, 6.130, 8.061, P < 0.05), while the anti-apoptotic proteins myeloid cell leukemia 1 protein (Mcl-1) and Bcl-2 showed upward trends ( Ftrend = 58.201, 7.691, P < 0.05). Compared with the 0 passage and the control group of the same passage, from the 22nd passage of caspase-3, cleaved-caspase-3, from the 15th passage of CHOP, Mcl-1, and Bcl-2, from the 29th passage of Bax in the arsenite group, the differences of protein were statistically significant ( P < 0.05). However, there were no significant differences in caspase-8, cleaved-caspase-8, caspase-12 and cleaved-caspase-12 protein expressions in the arsenic group ( P > 0.05). Compared with the 0 passage and the control group of the same passage, from the 8th passage of Nrf2 proteins in the arsenite group, the differences of expressions were statistically significant ( P < 0.05). Compared with T-HBE cells transfected with Con siRNA (control), the apoptosis rate of T-HBE cells transfected with Nrf2 siRNA was higher ( P < 0.05). Compared with T-HBE cells transfected with Con siRNA, the expression levels of Nrf2, Bcl-2 and Mcl-1 in T-HBE cells transfected with Nrf2 siRNA were lower ( P < 0.05), while the expression levels of cleaved-caspase-3/caspase-3, caspase-3, cleaved-caspase-3, CHOP, and Bax were higher ( P < 0.05). Conclusion:Nrf2 may regulate mitochondrial apoptotic pathway through Bcl-2, Mcl-1 and Bax, and endoplasmic reticulum apoptotic pathway through CHOP, so as to inhibit the apoptosis of HBE cells and participate in the process of malignant transformation of HBE cells induced by NaAsO 2.

Objective:To understand the clinical characteristics of pregnant women infected with dengue virus (DENV) in Ruili City, Yunnan Province, so as to provide basis for formulating effective diagnosis and treatment protocol of dengue fever in pregnant women.Methods:A total of 18 pregnant women infected with DENV hospitalized in Ruili People's Hospital in 2017 and 2018 were selected as observation group, and 18 non-pregnant women infected with DENV were selected as control group according to the age range of the observation group, and epidemiological and clinical data of patients in the two groups were retrospectively collected. Epidemiological characteristics, clinical symptoms and laboratory biochemical indexes of the two groups were compared and analyzed.Results:There were no significant differences ( t = - 0.032, 0.495, P > 0.05) in age [(27.9 ± 5.3) vs (27.9 ± 5.1) years old] and hospitalization stay [(6.8 ± 1.6) vs (6.6 ± 2.0) d] between the observation group and control group. One pregnant woman in observation group had early pregnancy abortion. Patients of both groups had fever in 18 cases (100.0%), headache, muscle aches, and chills in 14 cases (77.8%), anorexia in 15 cases (83.3%), and nausea and vomiting in 5 cases (27.8%); fatigue in 14 cases (77.8%) and 16 cases (88.9%), respectively; there was 1 case of rash in observation group (5.6%), and no rash in control group. There were no significant differences in the above mentioned clinical symptoms distribution between the two groups ( P > 0.05). On the first day of admission, the reduction proportions in red blood cells [61.1% (11/18) vs 5.6% (1/18)], hemoglobin [50.0% (9/18) vs 16.7% (3/18)], and hematocrit [61.1% (11/18) vs 16.7% (3/18)] in observation group were significantly higher than those in control group ( P < 0.05); on the fifth day of admission, the reduction proportions in hemoglobin [33.3% (6/18) vs 5.6% (1/18)] and hematocrit [33.3% (6/18) vs 5.6% (1/18)] in observation group were significantly higher than those in control group ( P < 0.05). Conclusions:The red blood cells, hemoglobin and hematocrit of pregnant women infected with DENV are significantly reduced, and there is a risk of miscarriage in early pregnancy. It is suggested that relevant departments should strengthen the training of medical staff to diagnose and treat pregnant women infected with DENV early.