Objective:To investigate the clinical efficacy of 3D printed guide plate-assisted hematoma puncture and catheter drainage in the treatment of a moderate volume of hypertensive intracerebral hemorrhage in the basal ganglia.Methods:The clinical data of 42 patients with a moderate volume of hypertensive intracerebral hemorrhage in the basal ganglia who received treatment with 3D printed guide plate-assisted hematoma puncture and catheter drainage in Dazhu Hospital of North Sichuan Medical College from January 2016 to January 2021 were retrospectively analyzed. In the traditional puncture group, there were 19 patients who received traditional punctures according to preoperative cranial CT findings (traditional puncture group). In the 3D printed guide plate puncture group, there were 23 patients who received hematoma puncture and catheter drainage assisted by a 3D printed guide plate. Preoperative preparation time (from admission to operation), operative time, the number of hematoma punctures, hematoma clearance rate, postoperative indwelling time of drainage tube, residual hematoma rate, the occurrence of puncture canal bleeding, intracranial infection, Glasgow Coma Scale score measured at 3 and 7 days after surgery, and Glasgow Outcome Scale score measured at 1, 3 and 6 months after surgery were compared between the two groups.Results:There were no significant differences in preoperative preparation time and operative time between the two groups ( t = 0.25, 0.40, both P > 0.05). 3D-printed guide plate-assisted hematoma puncture reduced the probability of reveiving one more hematoma puncture during the surgery. There was no significant difference in the number of hematoma puncture between the two groups ( χ2= 0.48, P > 0.05). There were no significant differences in the probabilities of puncture canal bleeding and intracranial infection between the two groups ( χ2 = 0.05, 0.03, both P > 0.05). Postoperative indwelling time of the drainage tube in the 3D printed guide plate puncture group was significantly shorter than that in the traditional puncture group [(3.10 ± 0.38) vs. (3.46 ± 0.52) days, t = 2.65, P < 0.05]. The residual hematoma rate in the 3D printed guide plate puncture group was significantly lower than that in the traditional puncture group [(32.04 ± 5.33)% vs. (37.37 ± 5.51)%, χ2 = 3.20, P < 0.05]. There were significant differences in Glasgow Coma Scale score measured at 3 and 7 days after surgery between the two groups [(12.04 ± 1.19) points vs. (11.26 ± 0.93) points, (13.65 ± 0.88) points vs. (12.94 ± 0.97) points, t = 2.33, 2.46, both P < 0.05]. Glasgow Outcome Scale score measured at 1, 3, and 6 months after surgery in the 3D printed guide plate puncture group was 18, 21, and 22 points, respectively, which was significantly higher than 9, 11, and 12 points in the traditional puncture group ( χ2 = 4.34, 4.69, 5.17, all P < 0.05). Conclusion:3D printed guide plate assisted hematoma puncture and catheter drainage for treatment of a moderate volume of hypertensive intracerebral hemorrhage in the basal ganglia can increase the accuracy of puncture, decrease hematoma residual rate, improve short- and long-term prognosis, does not prolong preoperative preparation time. Moreover, it costs low, is safe, and is easy to learn.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis is unlikely contained in the absence of effective therapeutics or vaccine. The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays essential roles in virus replication and immune evasion, presenting a charming drug target. Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology, inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development. In this study, we sought to provide structural frameworks for PLpro inhibitor design. We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111S, which shares many structural features of SARS-CoV PLpro. This crystal form has unique packing, high solvent content and reasonable resolution 2.5 Å, hence provides a good possibility for fragment-based screening using crystallographic approach. We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture. We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To investigate the value of preoperative three-dimensional image reconstruction in the treatment of ureteropelvic junction obstruction (UPJO). METHODS: We reviewed data on 40 patients (22 male cases, and 18 female cases) diagnosed with UPJO in Peking University First Hospital from May 2017 to April 2019. The median age was 26.5 years (IQR 23.25-38.75) years. There were 11 patients complicated with ectopic vessels, 14 patients with kidney stones, 3 patients with horseshoe kidney, and 6 patients with obstruction after pyeloplasty. All the patients underwent preoperative enhanced CT scan, and the CT data were reconstructed into three-dimensional image models. The obstruction position of ureteropelvic junction and the relationship between ureteropelvic junction and blood vessels and organs were observed by three-dimensional models to assist planning surgery. Thirty-seven patients underwent laparoscopic pyeloplasty (including 3 cases combined with pyelolithotomy with flexible cystoscope, 1 case combined with pyelolithotomy by sun-style cystoscope, 1 case with laparoscopic ureter resection and anastomosis, 3 cases of laparoscopic pyeloplasty of horseshoe kidney), 2 patients underwent laparoscopic ventral onlay lingual mucosal graft ureteroplasty, and 1 patient underwent robot-assisted laparoscopic pyeloplasty. RESULTS: Three-dimensional CT image clearly showed the relationship between the obstruction of ureteropelvic junction and blood vessels and organs after three-dimensional reconstruction. The type, diameter, position and direction of the ectopic vessels could be observed clearly before operation according to the three-dimensional reconstruction model, and the number, size, location and shape of renal calculi or other masses, the number of involved renal calyces and the anatomical distribution in the renal pelvis and calyces could be also evaluated preoperatively. After comprehensive analysis of the above information, individualized operation plans were performed on the patients, all the 40 cases were successfully completed with the surgery without any transfer to open surgery. The average operative time was (129.91±37.90) min (range: 75 to 273), the average blood loss was (48.1±78.0) mL (range: 10 to 400), the average hospitality was (5.04±1.99) d (range: 2 to 10), and the average postoperative drainage time was (3.8±1.4) d (range: 2 to 8). CONCLUSION The preoperative three-dimensional image reconstruction has a high clinical value in the treatment of ureteropelvic junction obstruction, and it is of great help to assist surgery planning and is worthy of further clinical promotion and application.
Adult ; Female ; Humans ; Imaging, Three-Dimensional ; Kidney Pelvis ; Laparoscopy ; Male ; Retrospective Studies ; Treatment Outcome ; Ureteral Obstruction/diagnostic imaging* ; Urologic Surgical Procedures ; Young Adult

OBJECTIVE: To summarize the experiences and outcomes of 108 robot-assisted laparoscopic upper urinary tract reconstruction surgeries conducted by a single surgeon. METHODS: We consecutively and retrospectively reviewed 108 patients who underwent robot-assisted laparoscopic upper urinary tract reconstruction surgeries by a single surgeon from November 2018 to January 2020. The patient demographics, perioperative variables, postoperative complications and follow-up data were recorded. Fifty-three modified dismembered pyeloplasties (MDP), 11 spiral flap pyeloplasties (SFP), 11 ure-teroureterostomies (UUT), 4 lingual mucosal onlay graft ureteroplasties (LMU), 5 appendiceal onlay flap ureteroplasties (AU), 11 ureteral reimplantations (UR), 6 Boari flap-Psoas hitch surgeries (BPS) and 7 ileal ureter replacements (IUR) were enrolled finally. The success was defined as the improvement in subjective pain levels, and the improvement in the degree of hydronephrosis at ultrasound. RESULTS: All the surgeries were successfully completed without open or laparoscopic conversion. The median operative time was 141 min (range: 74-368 min), median blood loss was 20 mL (range: 10-350 mL) and median hospital stay was 4 d (range: 3-19 d) in MDP group, with the success rate of 94.3%. The median operative time was 159 min (range: 110-222 min), median blood loss was 50 mL (range: 20-150 mL) and median hospital stay was 5 d (range: 3-8 d) in SFP group, with the success rate of 100%. The median operative time was 126 min (range: 76-160 d), median blood loss was 20 mL (range: 10-50 mL) and median hospital stay was 5 d (range: 4-9 d) in UUT group, with the success rate of 100%. The median operative time was 204 min (range: 154-250 min), median blood loss was 30 mL (range: 10-100 mL) and median hospital stay was 6 d (range: 4-7 d) in LMU group, with the success rate of 100%. The median operative time was 164 min (range: 135-211 min), median blood loss was 75 mL (range: 50-200 mL) and median hospital stay was 8.5 d (range: 6-12 d) in AU group, with the success rate of 100%. The median operative time was 149 min (range: 100-218 min), median blood loss was 20 mL (range: 10-50 mL) and median hospital stay was 7 d (range: 5-10 d) in UR group, with the success rate of 90.9%. The median operative time was 166 min (range: 137-205 min), median blood loss was 45 mL (range: 20-100 mL) and median hospital stay was 5 d (range: 4-41 d) in BPS group, with the success rate of 83.3%. The median operative time was 270 min (range: 227-335 min), median blood loss was 100 mL (range: 10-100 mL) and median hospital stay was 7 d (range: 5-26 d) in IUR group, with the success rate of 85.7%. CONCLUSIONS The surgeon performed and modified numerous complicated upper urinary tract reconstruction surgeries by the robotic platform, which facilitated the development of the standardized upper urinary tract reconstruction surgical technique.
Humans ; Laparoscopy ; Retrospective Studies ; Robotic Surgical Procedures ; Surgeons ; Treatment Outcome ; Ureter

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.
Animals ; Cell Cycle Proteins/genetics* ; Cell Line ; Cell Survival ; Chondroitin Sulfate Proteoglycans/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Gene Expression Regulation ; Gene Knockdown Techniques ; Infertility, Male ; Male ; Meiosis/genetics* ; Mice ; Mice, Knockout ; Mice, Transgenic ; Phosphate-Binding Proteins/genetics* ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics* ; Rad51 Recombinase/genetics* ; Real-Time Polymerase Chain Reaction ; Spermatocytes/metabolism* ; Spermatogenesis/genetics* ; Spermatogonia/metabolism*

ObjectiveTo make a preliminary investigation on the safety and efficacy of focused low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED).

METHODSWe treated 32 ED patients by focused LI-ESWT with the device of Medispec's ED1000. Before and at 4 and 12 weeks after treatment, we evaluated the erectile function of the patients using the International Index of Erectile Function-erectile function domain (IIEF-EF), Erection Hardness Score (EHS), Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), and Global Assessment Questionnaire questions 1 and 2 (GAQ1 and GAQ2), and recorded the incidence rate of adverse events.

RESULTSThe patients averaged 30.69 years of age. Compared with the baseline, the mean IIEF-EF score of the patients was significantly increased at 4 and 12 weeks after LI-ESWT (14.94 vs 20.97 and 21.47, P <0.01), and so were the EHS (1.75 vs 2.66 and 2.56, P <0.01) and the "Yes" answers to SEP2 (21.88% vs 68.75% and 71.88%), SEP3 (0 vs 43.75% and 56.25%), GAQ1 (NA vs 81.25% and 71.88%) and GAQ2 (NA vs 65.63% and 68.75%). The total effectiveness rates at 4 weeks and 12 weeks were 75% and 71.88% respectively. One of the patients felt penile shaft pain with mild ecchymosis after LI-ESWT but was recovered without special treatment a week later.

CONCLUSIONSLI-ESWT can significantly improve the erectile function of ED patients with no obvious adverse effects within 12 weeks after treatment.

Adult ; Double-Blind Method ; Ecchymosis ; etiology ; Erectile Dysfunction ; therapy ; Extracorporeal Shockwave Therapy ; adverse effects ; methods ; Humans ; Male ; Pain, Procedural ; Penile Erection ; physiology ; Surveys and Questionnaires ; Treatment Outcome

Objective To understand the hepatitis C virus (HCV) genotype distribution in Yantai district of Shandong province,and to explore whether the HCV genotypes was relevant to the injure of liver through the index of liver function.Methods Using specific PCR primers to amplify the HCV RNA 5' UTR/NS5B,then PCR products were sequenced by genetic analyzer.The genotypes were identified by alignment to the GenBank reference sequences and construction the phylogenetic tree of 5 ' UTR.Results Among 9 unpaid blood donors we detected two kinds of genotypes of 1b and 3a,respectively,8 cases (88.9％) and 1 case (11.1％).Among 33 cases of hepatitis C patients we detected the lb,2a and 6a the three kinds of genotypes,respectively,22 (66.7％),10 (30.3％ ) and 1 (3.03％) cases.Subtype 1b is the advantage of popular genotype in HCV carriers from Yantai district,and the distribution of 1b was no significant difference in the different population (x2 =0.796,P =0.373 ) ; The difference of indicator of liver damage in the different genotypes of subjects were significant ( P ＜ 0.05 ),the mean of ALT,AST of 2asubtype carriers was significantly higher than the 1 b-subtype population.Conclusions The genetic diversity of HCV in Shandong Yantai district was presented.The main genotypes were 1b-subtype,and 3a and 6asubtype was detected firstly.The genotype of HCV were relevant to the liver damage indicators,2a-subtype hepatitis C virus infection in the liver cells may play an important role in the disease process.

Objective To explore the variations of gene C in hepatitis B viruses between hepatitis B patients and healthy carriers, and provide experimental evidences for analysis of virus gene mutations acting on the virus material science and response of the body to the virus. MethodsThe virus DNA load in hepatitis B patients and healthy blood donors was investigated by real-time polymerase chain reaction (PCR). Gene sequence analysis was taken to detect gene polymorphism, and all the success samples were compaired with standard strain by DNAstar. Results(①)Compared with standard strain, C region in all samples had mutations, there were 31 mutations in at least 2 samples (3 mutations in gene PreC and 28 mutations in gene C), including 9 missense mutations, 1 chain termination mutation and 21 synonymous mutation. Mutations nt 1827 c→a and nt 2221 c→t existed in all the samples, and most samples had 6synonymous mutations. Four hepatitis B patients had mutation nt1896 g→a, and another 4 patients had 2mutations, namely, S87G and I97F (or I97L) in HBcAg CTL recognition episome. ②The success ratio of amplification and sequencing of HBV DNA was closely associated with its copy numbers. In the present study, copy numbers of HBV DNA which were successfully amplified and sequenced were almost more than 40 193/ml. ConclusionsHBV genome were easily affected by nucleotide mutations, 2 residues had mutations in gene of C region, which is firstly reported, suggesting these mutations may be geographical restricted. Mutations in gene of C region may either change the structure and function of HBeAg and HBcAg,which may further induce the escape of immune clearance for HBV or influence the detection of HBsAg or HBeAg, which may creat new problems for the prevention, diagnosis and treatment of hepatitis B.