Clinical research on rare diseases has always faced multiple challenges in clinical research design and implementation due to small sample sizes of patients,high heterogeneity,and limited research resources.The rapid development of digital intelligence technology has provided innovative solutions for rare disease research.This article systematically explores the current status and response strategies of clinical research on rare diseases in the digital intelligence age.On the one hand,the efficiency of rare disease research has been optimized through adaptive design,mixed trial mode,and precision medicine stratification methods.On the other hand,solutions based on digital technology have been proposed to address the practical challenges of recruitment difficulties and underrepresentation of rare disease clinical research patients,data management and technical barriers,and insufficient coverage of natural medical history and baseline databases through digital intelligence technology.By combining international collaboration,intelligent screening,and remote experiments,a multidisciplinary collaboration and international cooperation,adaptive design,digital data platform,and patient-centered remote research model have been constructed as the core implementation strategies.Typical cases demonstrate that digital intelligence technology not only effectively shortens the drug development cycle,but also significantly enhances patient benefits,providing a replicable practical paradigm for global rare disease research.The practice of digital platforms represented by the International Rare Disease Research Alliance and the China Rare Disease Diagnosis and Treatment Collaboration Network has further verified the feasibility and promotional value of the digitalization path.In summary,digital intelligence technology has shown considerable promise in overcoming the clinical research challenges of rare diseases and accelerating the development of treatment plans,providing systematic references for researchers,regulatory agencies,and patient organizations.It is expected to drive the clinical research of rare diseases towards a more efficient and accurate future.

Clinical research on rare diseases has always faced multiple challenges in clinical research design and implementation due to small sample sizes of patients,high heterogeneity,and limited research resources.The rapid development of digital intelligence technology has provided innovative solutions for rare disease research.This article systematically explores the current status and response strategies of clinical research on rare diseases in the digital intelligence age.On the one hand,the efficiency of rare disease research has been optimized through adaptive design,mixed trial mode,and precision medicine stratification methods.On the other hand,solutions based on digital technology have been proposed to address the practical challenges of recruitment difficulties and underrepresentation of rare disease clinical research patients,data management and technical barriers,and insufficient coverage of natural medical history and baseline databases through digital intelligence technology.By combining international collaboration,intelligent screening,and remote experiments,a multidisciplinary collaboration and international cooperation,adaptive design,digital data platform,and patient-centered remote research model have been constructed as the core implementation strategies.Typical cases demonstrate that digital intelligence technology not only effectively shortens the drug development cycle,but also significantly enhances patient benefits,providing a replicable practical paradigm for global rare disease research.The practice of digital platforms represented by the International Rare Disease Research Alliance and the China Rare Disease Diagnosis and Treatment Collaboration Network has further verified the feasibility and promotional value of the digitalization path.In summary,digital intelligence technology has shown considerable promise in overcoming the clinical research challenges of rare diseases and accelerating the development of treatment plans,providing systematic references for researchers,regulatory agencies,and patient organizations.It is expected to drive the clinical research of rare diseases towards a more efficient and accurate future.

Objective:To investigate the clinical characteristics and pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients complicated with pulmonary filamentous fungal infection in Guangdong Province, so as to provide evidences for improving the diagnosis and treatment.Methods:A total of 143 AIDS patients with pulmonary filamentous fungal infection hospitalized in Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 2016 to December 2018 were included. The filamentous fungi cultured in bronchoalveolar lavage fluid of these patients were identified with morphological and molecular biological methods. And their clinical characteristics were analyzed. Nonparametric Kruskal-Wallis H test and chi-square test were used for statistical analysis. Results:Among the 143 patients, 116(81.1%) had fever, 104(72.7%) had cough, 83(58.0%) had expectoration, and 59(41.3%) had anhelation. The CD4 + T lymphocyte count was 22.0(9.3, 60.8) cells/μL and 118(82.5%) cases were below 100.0 cells/μL. The white blood cell counts decreased in 52(36.4%) cases and increased in 18(12.6%) cases, anemia was found in 109(76.2%) cases, platelet count decreased in 29(20.3%) cases. Sixty-four (44.8%) cases were positive for galactomannan test. Chest computed tomography showed diffuse infection of both lungs in 114(79.7%) cases, miliary changes in 12(8.4%) cases, pleural effusion in 44(30.8%) cases, and enlargement of pleural and (or) mediastinal lymph nodes in 45(31.5%) cases. After receiving antifungal therapy, 124 (86.7%) cases were cured or improved, and 19 (13.3%) cases were discharged automatically or died of disease deterioration. Among the 143 strains of filamentous fungi, there were 56 strains of Aspergillus species pluralis (39.2%, including 24 strains of Aspergillus fumigatus), 37 strains of Talaromyces marneffei ( T. marneffei) (25.9%), 22 strains of Penicilium species pluralis (15.4%), and 28 strains of other genera of filamentous fungi (19.6%). The median CD4 + T lymphocyte counts in patients infected with Aspergillus species pluralis, T. marneffei, Penicilium species pluralis and other genera were 24.5, 15.0, 53.5 and 22.0 cells/μL, respectively, and the difference was statistically significant ( H=11.282, P=0.010). The proportions of AIDS patients with different pulmonary filamentous fungal infection of CD4 + T lymphocyte count ≤50.0 cells/μL in descending order were T. marneffei group (89.2%(33/37)), Aspergillus species pluralis group and other genera group (67.9%(38/56), 67.9%(19/28)), and Penicillium species pluralis group (54.5%(12/22)), and the difference was statistically significant ( χ2=9.296, P=0.026). Conclusions:The clinical manifestations of pulmonary filamentous fungal infection in AIDS patients in Guangdong Province are not specific. The pathogenic spectrum contains various genera, and T. marneffei and Aspergillus fumigatus are dominant, which could be correlated with CD4 + T lymphocyte count.

Objective:To explore the protective effect of nerve plane-oriented laparoscopic total mesorectal excision (NPO+ LTME) for postoperative urinary and sexual function in patients with rectal cancer.Methods:Retrospective analysis was performed on rectal cancer patients who received surgical treatment at Renmin Hospital of Wuhan University from Jan 2016 to Dec 2018, including 114 patients in the NPO+ LTME group and 92 patients in the laparoscopic TME combined with pelvic autonomic nerve preservation (LTME+ PANP) group. Surgical and tumor-related indicators were recorded and compared between the two groups, and postoperative urination and sexual function were followed up.Results:There was no significant difference in baseline indicators between the two groups ( P>0.05). The operative time of the two groups was (150±7) min and (154±7) min, respectively ( t=3.585, P<0.05). Intraoperative bleeding was (9±3) ml and (15±6) ml ( t=7.654, P<0.05), respectively.Three months after surgery, the rate of urinary dysfunction in the NPO+ LTME group was lower than that in the LTME+ PANP group ( Z=2.549, P<0.05), but there was no difference between the two groups 6 and 12 months after surgery ( Z=0.814, P>0.05 and Z=1.275, P>0.05). At 3, 6 and 12 months after surgery, the erectile function in NPO+ LTME group was better than that in LTME+ PANP group ( Z=4.917, P<0.05; Z=4.947, P<0.05 and Z=4.081, P<0.05); The rate of ejaculation dysfunction was also lower than that of the LTME+ PANP group ( Z=4.464, P<0.05; Z=4.948, P<0.05 and Z=4.434, P<0.05); In addition, postoperative female sexual function was superior to LTME+ PANP group ( Z=2.532, P<0.05; Z=2.364, P<0.05; Z=2.076, P<0.05). Conclusion:NPO+ LTME has good surgical safety and also has certain advantages for patient sexual function and early urinary function protection.

Betacoronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Single-Cell Analysis

Objective: Using previous total mesorectal excision with pelvic autonomic nerve preservation (PANP+TME) and simple total mesorectal excision (TME) without emphasis on retained nerves as control, we explore the advantages of nerve plane-oriented laparoscopic total mesorectal excision (NPO+LTME) on urinary and sexual function. Methods: A retrospective cohort study was carried out. Case inclusion criteria: (1) male patients with pathologically confirmed middle and low rectal adenocarcinoma (4 to 11 cm from the anus); (2) stage T1-2tumor; (3) normal sexual life before operation. Exclusion criteria: (1) no pathological diagnosis before surgery; (2) local recurrence or distant metastasis; (3) preoperative neoadjuvant chemoradiotherapy; (4) opensurgery and laparoscopic surgery conversionto open; (5) no follow-up data. According to the above criteria, clinical data of 173 male patients with low and middle rectal adenocarcinoma who underwent radical operation for laparoscopic rectal cancer from July 2003 to July 2018 at the Department of Gastrointestinal Surgery, Wuhan University People′s Hospital were collected. According to different surgical methods, patients were divided into TME group (58 cases), PANP+TME group (63 cases) and NPO+LTME group (52 cases). There were no significant differences in the baseline data including age, body mass index and pathological examination between the 3 groups (all P>0.05). The nerve plane referred to the nerve, the adipose tissue, the extremely finecapillaries around the nerve with overlying fine membranous tissue. NPO+LTME referred to the process of laparoscopic TME guided by the nerve plane, performing in the loose connective tissue between the nerve plane and the rectal properfascia, in order to ensure the integrity of the nerve plane, and maximally protect the patient's urinary and reproductive functions. The operation time, intraoperative blood loss, urinary catheter removal time, urinary function grading, postoperative first erection time, and erectile function and ejaculation function were observed and compared among the 3 groups at 3- and 6-month after operation. Results: In the NPO+LTME group, the PANP+TME group and the TME group, the operation time was (181.9±24.5) minutes, (176.7±29.2) minutes and (137.7±16.2) minutes, respectively (F=54.868, P<0.001); the intraoperative blood lost was (6.0±1.4) ml, (6.5±1.8) ml and (12.8±4.6) ml, respectively (F=95.016, P<0.001); the time to postoperative removal of the catheter was (2.4±1.1) days, (3.7 ±1.7) days and (6.5±2.4) days, respectively (F=79.409, P<0.001); the first postoperative erection time was (1.6±0.6) days, (8.9±2.7) days and (15.9±6.8) days (F=177.677, P<0.001), respectively, whose differences were all statistically significant (all P<0.01). In comparison of urinary function grading, the proportion of grade I (normal function, no urinary dysfunction) in the NPO+LTME, the ANP+TME group and the TME group was 84.1% (53/63), 39.7% (23/58) and 19.2% (10/52), respectively, and the difference was statistically significant (H=52.915, P<0.001). At postoperative 3- and 6-month, proportion of patients with grade I erectile function (normal erectile function) was 77.8% (49/63) and 85.7% (54/63), 44.8% (26/58) and 53.4% (31/58), 28.8% (15/52) and 48.1% (25/52) in the NPO+LTME group, the PANP+TME group, and the TME group, respectively. The differences were statistically significant (H=91.709, P<0.001; H=79.692, P<0.001). The proportion of patients with grade I ejaculation function (with ejaculation, no abnormalities in routine semen examination before and after surgery) at 3- and 6-month after surgery in the NPO+LTME group, the PANP+TME group and the TME group was 82.5% (52/63) and 87.3% (55/63), 53.4% (31/58) and 60.3% (35/58), 28.8% (15/52) and 46.1% (24/52), respectively. The differences were statistically significant as well (H=86.543, P<0.001; H=78.667, P<0.001). Patients in the NPO+LTME group had no grade III erections and ejaculation disorders. Conclusion The surgical procedure of NPO+LTME can promote the recovery of postoperative neurological function and preserve urination and sexual function better.

Objective Using previous total mesorectal excision with pelvic autonomic nerve preservation (PANP+TME) and simple total mesorectal excision (TME) without emphasis on retained nerves as control, we explore the advantages of nerve plane?oriented laparoscopic total mesorectal excision (NPO+LTME) on urinary and sexual function. Methods A retrospective cohort study was carried out. Case inclusion criteria: (1) male patients with pathologically confirmed middle and low rectal adenocarcinoma (4 to 11 cm from the anus); (2) stage T1?2tumor; (3) normal sexual life before operation. Exclusion criteria: (1) no pathological diagnosis before surgery; (2) local recurrence or distant metastasis; (3) preoperative neoadjuvant chemoradiotherapy; (4) opensurgery and laparoscopic surgery conversionto open; (5) no follow?up data. According to the above criteria, clinical data of 173 male patients with low and middle rectal adenocarcinoma who underwent radical operation for laparoscopic rectal cancer from July 2003 to July 2018 at the Department of Gastrointestinal Surgery, Wuhan University People′ s Hospital were collected. According to different surgical methods, patients were divided into TME group (58 cases), PANP+TME group (63 cases) and NPO+LTME group (52 cases). There were no significant differences in the baseline data including age, body mass index and pathological examination between the 3 groups (all P>0.05). The nerve plane referred to the nerve, the adipose tissue, the extremely finecapillaries around the nerve with overlying fine membranous tissue. NPO+LTME referred to the process of laparoscopic TME guided by the nerve plane, performing in the loose connective tissue between the nerve plane and the rectal properfascia, in order to ensure the integrity of the nerve plane, and maximally protect the patient's urinary and reproductive functions. The operation time, intraoperative blood loss, urinary catheter removal time, urinary function grading, postoperative first erection time, and erectile function and ejaculation function were observed and compared among the 3 groups at 3?and 6?month after operation. Results In the NPO+LTME group, the PANP+TME group and the TME group, the operation time was (181.9±24.5) minutes, (176.7± 29.2) minutes and (137.7±16.2) minutes, respectively (F=54.868, P<0.001); the intraoperative blood lost was (6.0 ± 1.4) ml, (6.5 ± 1.8) ml and (12.8 ± 4.6) ml, respectively (F=95.016, P<0.001); the time to postoperative removal of the catheter was (2.4±1.1) days, (3.7 ±1.7) days and (6.5±2.4) days, respectively (F=79.409, P<0.001); the first postoperative erection time was (1.6±0.6) days, (8.9±2.7) days and (15.9±6.8) days (F=177.677, P<0.001), respectively, whose differences were all statistically significant (all P<0.01). In comparison of urinary function grading, the proportion of grade I (normal function, no urinary dysfunction) in the NPO+LTME, the ANP+TME group and the TME group was 84.1% (53/63), 39.7% (23/58) and 19.2% (10/52), respectively, and the difference was statistically significant (H=52.915, P<0.001). At postoperative 3?and 6?month, proportion of patients with grade I erectile function (normal erectile function) was 77.8% (49/63) and 85.7% (54/63), 44.8% (26/58) and 53.4% (31/58), 28.8% (15/52) and 48.1% (25/52) in the NPO+LTME group, the PANP+TME group, and the TME group, respectively. The differences were statistically significant (H=91.709, P<0.001; H=79.692, P<0.001). The proportion of patients with grade I ejaculation function (with ejaculation, no abnormalities in routine semen examination before and after surgery) at 3?and 6?month after surgery in the NPO+LTME group, the PANP+TME group and the TME group was 82.5% (52/63) and 87.3% (55/63), 53.4% (31/58) and 60.3% (35/58), 28.8% (15/52) and 46.1% (24/52), respectively. The differences were statistically significant as well (H=86.543, P<0.001; H=78.667, P<0.001). Patients in the NPO+LTME group had no grade III erections and ejaculation disorders. Conclusion The surgical procedure of NPO + LTME can promote the recovery of postoperative neurological function and preserve urination and sexual function better.

Objective Using previous total mesorectal excision with pelvic autonomic nerve preservation (PANP+TME) and simple total mesorectal excision (TME) without emphasis on retained nerves as control, we explore the advantages of nerve plane?oriented laparoscopic total mesorectal excision (NPO+LTME) on urinary and sexual function. Methods A retrospective cohort study was carried out. Case inclusion criteria: (1) male patients with pathologically confirmed middle and low rectal adenocarcinoma (4 to 11 cm from the anus); (2) stage T1?2tumor; (3) normal sexual life before operation. Exclusion criteria: (1) no pathological diagnosis before surgery; (2) local recurrence or distant metastasis; (3) preoperative neoadjuvant chemoradiotherapy; (4) opensurgery and laparoscopic surgery conversionto open; (5) no follow?up data. According to the above criteria, clinical data of 173 male patients with low and middle rectal adenocarcinoma who underwent radical operation for laparoscopic rectal cancer from July 2003 to July 2018 at the Department of Gastrointestinal Surgery, Wuhan University People′ s Hospital were collected. According to different surgical methods, patients were divided into TME group (58 cases), PANP+TME group (63 cases) and NPO+LTME group (52 cases). There were no significant differences in the baseline data including age, body mass index and pathological examination between the 3 groups (all P>0.05). The nerve plane referred to the nerve, the adipose tissue, the extremely finecapillaries around the nerve with overlying fine membranous tissue. NPO+LTME referred to the process of laparoscopic TME guided by the nerve plane, performing in the loose connective tissue between the nerve plane and the rectal properfascia, in order to ensure the integrity of the nerve plane, and maximally protect the patient's urinary and reproductive functions. The operation time, intraoperative blood loss, urinary catheter removal time, urinary function grading, postoperative first erection time, and erectile function and ejaculation function were observed and compared among the 3 groups at 3?and 6?month after operation. Results In the NPO+LTME group, the PANP+TME group and the TME group, the operation time was (181.9±24.5) minutes, (176.7± 29.2) minutes and (137.7±16.2) minutes, respectively (F=54.868, P<0.001); the intraoperative blood lost was (6.0 ± 1.4) ml, (6.5 ± 1.8) ml and (12.8 ± 4.6) ml, respectively (F=95.016, P<0.001); the time to postoperative removal of the catheter was (2.4±1.1) days, (3.7 ±1.7) days and (6.5±2.4) days, respectively (F=79.409, P<0.001); the first postoperative erection time was (1.6±0.6) days, (8.9±2.7) days and (15.9±6.8) days (F=177.677, P<0.001), respectively, whose differences were all statistically significant (all P<0.01). In comparison of urinary function grading, the proportion of grade I (normal function, no urinary dysfunction) in the NPO+LTME, the ANP+TME group and the TME group was 84.1% (53/63), 39.7% (23/58) and 19.2% (10/52), respectively, and the difference was statistically significant (H=52.915, P<0.001). At postoperative 3?and 6?month, proportion of patients with grade I erectile function (normal erectile function) was 77.8% (49/63) and 85.7% (54/63), 44.8% (26/58) and 53.4% (31/58), 28.8% (15/52) and 48.1% (25/52) in the NPO+LTME group, the PANP+TME group, and the TME group, respectively. The differences were statistically significant (H=91.709, P<0.001; H=79.692, P<0.001). The proportion of patients with grade I ejaculation function (with ejaculation, no abnormalities in routine semen examination before and after surgery) at 3?and 6?month after surgery in the NPO+LTME group, the PANP+TME group and the TME group was 82.5% (52/63) and 87.3% (55/63), 53.4% (31/58) and 60.3% (35/58), 28.8% (15/52) and 46.1% (24/52), respectively. The differences were statistically significant as well (H=86.543, P<0.001; H=78.667, P<0.001). Patients in the NPO+LTME group had no grade III erections and ejaculation disorders. Conclusion The surgical procedure of NPO + LTME can promote the recovery of postoperative neurological function and preserve urination and sexual function better.

Objective To investigate the causes,diagnosis and treatment of small intestine bleeding.Methods Sixty-eight cases of small intestine bleeding from January 2000 to June 2010 were retrospectively analyzed.Among all cases,4 underwent routine hemostatic treatment under colonoscopy,40treated with open surgery and 24 patients with laparoscopic therapy.Among them,57 cases underwent part resection for some small intestine,completely laparoscopic resection of diverticula was performed in 7patients.Results Neoplasms was the leading cause of small intestine bleeding,accounting for 48.5％ (33/68)in these patients,followed by small intestine diverticulum accounted for 29.4％ ( 20/68 ),intestinal infective diseases accounted for 14.7％ ( 10/68 ) and vascular disease accounted for 7.4％ ( 5/68 ).Conclusion The clinical manifestations of small intestinal bleeding showed no specific signs.Neoplasm,intestine diverticulum and intestinal infective diseases are the most common causes of small intestinal bleeding.Small intestinal bleeding can be diagnosed in intraoperative colonoscopy.Surgery is the most effective treatment for small intestinal bleeding.