A binary pulsar in a 53-minute orbit.

Spider pulsars are neutron stars that have a companion star in a close orbit. The companion star sheds material to the neutron star, spinning it up to millisecond rotation periods, while the orbit shortens to hours. The companion is eventually ablated and destroyed by the pulsar wind and radiation1,2. Spider pulsars are key for studying the evolutionary link between accreting X-ray pulsars and isolated millisecond pulsars, pulsar irradiation effects and the birth of massive neutron stars3-6. Black widow pulsars in extremely compact orbits (as short as 62 minutes7) have companions with masses much smaller than 0.1 M⊙. They may have evolved from redback pulsars with companion masses of about 0.1-0.4 M⊙ and orbital periods of less than 1 day8. If this is true, then there should be a population of millisecond pulsars with moderate-mass companions and very short orbital periods9, but, hitherto, no such system was known. Here we report radio observations of the binary millisecond pulsar PSR J1953+1844 (M71E) that show it to have an orbital period of 53.3 minutes and a companion with a mass of around 0.07 M⊙. It is a faint X-ray source and located 2.5 arcminutes from the centre of the globular cluster M71.

A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

No pulsed radio emission during a bursting phase of a Galactic magnetar.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

[The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain].

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians' awareness of opportunistic virus reactivation during anti-tumor treatment.

[Characteristics and clinical analysis of MLH1 c.463dupC gene mutation in a Lynch syndrome family].

In this study, a case of Lynch syndrome (LS) family line with a novel mutation site in the MLH1 c.463dupC gene was reported and the clinical and pathogenic genetic features of this family were analyzed. A 40-year-old female patient with colon cancer diagnosed at the First Affiliated Hospital of Kunming Medical University on October 2, 2020 was retrospectively included. The clinical data of the family were collected and the family lineage was drawn. The family tumor history met the Amsterdam Criteria Ⅱ and the diagnostic criteria of LS in Chinese, which was a typical LS family lineage. A germline code-shift missense mutation c.463dupC in the MLH1 gene located in exon 6, a possible pathogenic variant, was detected by second-generation sequencing (NGS) in the patient. Subsequently, Sanger sequencing was performed on a total of 20 direct lineage members of the family of the MLH1 gene, 7 cases were found to harbor the mutation and included in the LS high-risk control. Follow-up to October 2023 showed that the patient had endometrial and cervical polyps, one case had colorectal cancer, and two cases had intestinal polyps, all were treated with early intervention and therapy; two cases did not show any clinical symptoms. This study is the first to report a new mutation site for the potentially pathogenic MLH1 c.463dupC, providing a rationale for the pathogenicity of the mutation and standardized health management for familial carriers.

[Efficacy of sutureless intrascleral intraocular lens fixation with the modified Yamane technique].

Objective: To evaluate the efficacy of sutureless intrascleral intraocular lens (IOL) fixation with the modified Yamane technique. Methods: It was a retrospective case series study. Patients undergoing sutureless intrascleral IOL fixation with the modified Yamane technique were included at Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University from January 2022 to September 2023. Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), recorded as the logarithm of the minimum angle of resolution (logMAR), were measured before surgery and at 1 day, 3 days, 1 week, 1 month, and 3 months postoperatively. Refractive error and intraocular pressure were also checked. Anterior segment examination with a slit lamp microscope, fundus examination, anterior segment and posterior segment optical coherence tomography were performed. Intraoperative and postoperative ocular complications were documented. Results: A total of 53 patients (53 eyes) were included in this study, comprising 40 males and 13 females, with a median age of 60 (49, 68) years. Among them, the proportion of a history of trauma was 22.6% (12/53). There was 1 eye with intraoperative vitreous hemorrhage (1.9%). All eyes had no obvious hypotony, no obvious inflammation in the anterior chamber, and no pupillary abnormalities at 1 week after surgery. The mean follow-up time was (8.0±3.3) months (range, 3 to 16 months). There was no iris capture, re-dislocation, or haptic exposure of the IOL during the follow-up. The corneal endothelial cell density was (2 236±704) cells/mm2 preoperatively and (1 964±628) cells/mm2 at 1 month, with significant difference (P<0.001). The UCVA (logMAR) was 1.53±0.75 preoperatively, 0.18±0.17 at 1 month, 0.15±0.14 at 3 months, and 0.14±0.13 at the final visit (P<0.001). The UCVA (logMAR) at 1 month was significantly different from that at 3 months and the final visit (both P<0.05). At 1 month, 50.9% (27/53) of the eyes had an UCVA (logMAR)≤0.1, and the rate was 56.6% (30/53) at 3 months. The BCVA (logMAR) was 0.25±0.21, 0.03±0.06, 0.02±0.06, and 0.02±0.06 before surgery, at postoperative1 month, 3 months, and the final visit, respectively (P<0.001). The BCVA (logMAR) at 1 month was not significantly different from that at 3 months and the final visit (both P>0.05). The rate of the eyes with a BCVA (logMAR)≤0 was 81.1% (43/53) at 1 month and 83.0% (44/53) at 3 months. The IOL tilt was (5.18±2.60)° at postoperative 1 month and (5.08±2.48)° at postoperative 3 months, without statistically significant difference (P>0.05). The IOL decentration was (0.35±0.24) mm at postoperative 1 month and (0.32±0.24) mm at postoperative 3 months, without statistically significant difference (P>0.05). Conclusion: Sutureless intrascleral IOL fixation with the modified Yamane technique is simpler and more minimally invasive to achieve a stable and centered IOL implantation with fewer complications and good visual prognosis.

Impaired ascending aortic elasticity in fetuses with tetralogy of Fallot.

OBJECTIVES: Aortic wall stiffness has been reported in infants with tetralogy of Fallot (ToF) and may contribute to long-term aortic dilation even after corrective repair surgery. However, little is known about aortic elasticity in fetuses with ToF and the association with neonatal aortic dilation. The objectives of this study were to assess measures of elasticity of the ascending aorta (AAo) in fetuses with ToF and explore the association with neonatal aortic annular dilation in this population. METHODS: Seventy-six singleton fetuses with ToF and 76 control fetuses of singleton low-risk pregnancies were enroled into this prospective study. Fetal measures of AAo elasticity, including mean longitudinal strain (MLS), global circumferential strain (GCS) and fractional area change (FAC), were assessed by velocity vector imaging. The z-score of the aortic valve (AV) diameter at the level of the annulus, as a measure of aortic annular dilation, was determined in newborns. Logistic regression analysis was used to investigate the association between fetal measures of AAo elasticity and neonatal aortic annular dilation (defined as an AV annular z-score > 2) in cases with ToF identified prenatally. RESULTS: Median MLS, GCS and FAC in fetuses with ToF were lower than those in normal fetuses (7.52% vs 12.15% for MLS, 22.05% vs 29.73% for GCS and 34.2% vs 48.3% for FAC, all P < 0.001). Aortic annular dilation was present in 53/76 (69.7%) newborns with ToF. After adjustment for gestational age at fetal echocardiography and birth weight, fetal MLS, GCS and FAC were independently associated with aortic annular dilation neonatally, with odds ratios of 0.66, 0.78 and 0.82, respectively (P < 0.05). The best cut-off values of these prenatal measures of AAo elasticity for predicting neonatal aortic annular dilation in fetuses with ToF were 9.02% for MLS, 23.56% for GCS and 37.2% for FAC (P < 0.001), with areas under the receiver-operating-characteristics curves of 0.94, 0.91 and 0.93, respectively. CONCLUSION: Measures of AAo elasticity are decreased in fetuses with ToF. Impaired AAo elasticity in the fetal period is associated with aortic annular dilation postnatally. Additional research is needed to evaluate the relationship between the AAo elasticity injury pattern and degeneration of AAo elasticity under stress as well as the long-term outcome in this population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Visualizable intracardiac flow pattern in fetuses with congenital heart defect: pilot study of blood speckle-tracking echocardiography.

OBJECTIVES: Blood-flow pattern is an essential factor in cardiovascular development. Recently, blood speckle-tracking echocardiography (BST) based on high-frame-rate ultrasound has emerged as a promising technique for the assessment of blood-flow patterns and properties. The objectives of this study were to determine the feasibility of BST in the fetus and to assess intracardiac blood-flow patterns of fetuses with a congenital heart defect (CHD) using this technique. METHODS: This was a prospective study consisting of 35 normal fetuses, 35 fetuses with left-sided obstructive lesion (LSOL) and 35 fetuses with right-sided obstructive lesion (RSOL). BST images of fetal intracardiac regions of interest (ROIs), including the left ventricle (LV), right ventricle (RV), ascending aorta (AAo), aortic arch (AA), descending aorta (DAo) and pulmonary artery (PA), were obtained and analyzed. The feasibility of BST was assessed, and blood-flow pattern and number of vortices in the ROIs were recorded. RESULTS: The median gestational age of the fetuses was 24.7 weeks (range, 19.6-34.3 weeks). BST was feasible in 81.6% of cases, and the cut-off value of depth for an adequate BST image was ≤ 7.9 cm. There were no differences in the presence of vortex/turbulent blood flow in the LV or RV among the three groups. Vortex/turbulent blood flow in the AAo was detected in 0% (0/35), 14.3% (5/35) and 57.1% (20/35) of cases in the control, LSOL and RSOL groups, respectively. The respective values were 5.7% (2/35), 14.3% (5/35) and 51.4% (18/35) for the AA; 0% (0/35), 48.6% (17/35) and 0% (0/35) for the DAo; and 0% (0/35), 40.0% (14/35) and 51.4% (18/35) for the PA. With the exception of the DAo in the RSOL group, vortex/turbulent flow in the great artery ROIs was significantly more common in the LSOL and RSOL groups than in controls (P < 0.01). In the LSOL group, the number of vortices in the AAo, AA, DAo and PA was significantly greater compared with that in controls (P < 0.01). In the RSOL group, the number of vortices in the LV, AAo, AA and PA was significantly greater compared with that in controls (P < 0.01). CONCLUSIONS: Fetuses with CHD were more likely to exhibit vortex/turbulent blood flow and increased number of vortices in the great arteries compared with healthy controls. Further research is needed to determine the biomechanical effect of blood-flow patterns, especially vortex flow, on fetal cardiovascular structure and function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

[The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells].

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and ß-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

[Clinical and molecular characteristics and prognosis of classical hairy cell leukemia and hairy cell leukemia variant].

Objective: To evaluate the clinical characteristics, treatment response, and outcomes in patients with classical hairy cell leukemia (cHCL) and HCL variant (HCL-V). Methods: This is a retrospective case series study. Between January 2011 and December 2021, clinical data of 30 patients newly with diagnosed HCL at Peking Union Medical College Hospital were analyzed. The main outcome measures include clinical characteristics, treatment efficacy and survival. The Kaplan-Meier method was used for survival analysis. Results: Twenty-one cases of cHCL and 9 cases of HCL-v were included. The median age at diagnosis was 55.5 (range, 30-86) years, with the ratio of male to female 2.75∶1. The main clinical manifestations included fatigue in 11 cases (36.7%), abdominal distension in 7 cases (23.3%), and infection in 4 cases, while 8 cases were asymptomatic. Splenomegaly was reported in 24 cases (80.0%), including 7 (23.3%) with megalosplenia. The white blood cell count, lymphocyte count, and the proportion of peripheral hairy cells in HCL-v group were significantly higher than those in cHCL group, whereas the development of anemia, thrombocytopenia, and monocytopenia in cHCL group was more remarkable than that in HCL-v group (all P<0.05). The BRAF-V600E gene mutation was detected only in cHCL patients (11/14 vs. 0/9, P<0.001). In terms of immunophenotype, the expression of CD25, CD103, CD123 and CD200 in cHCL group (20/20, 20/20, 4/7, 7/17) were all stronger than those in HCL-v group (3/9, 7/9, 0/4, 2/8). Twenty-two patients were treated, of which 13 cases (12 cases of cHCL and 1 case of HCL-v) with cladribine, and 9 cases (4 cHCL and 5 HCL-v) with interferon. Complete remission rate and overall response rate were comparable between cladribine and interferon treatment groups (both P<0.05). The median follow-up time was 31 (range, 1-125) months, and the median overall survival (OS) of the entire group was 125 months. The 5-year OS rate in HCL-v patients represented a trend of inferior (50.0% vs. 95.0%, P=0.207). Conclusions: The clinical features of HCL are unspecific, which includes fatigue, splenomegaly and recurrent infection. The clinical features, immunophenotype, treatment response and prognosis of HCL-v are different from those of cHCL. BRAF-V600E gene mutation is suggested as a key marker for differential diagnosis. Cladribine is recommended as front-line regimen of cHCL patients with satisfactory efficacy and prognosis. Conversely, response and clinical outcome in HCL-v patients still need to be improved.

[Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone].

Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses. Results: A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) (χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy (HR=0.11, 95%CI 0.05-0.27), achievement of efficacy of partial response or better (HR=0.47, 95%CI 0.34-0.66), and non-aggressive relapse (HR=0.25, 95%CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion: In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

[Evaluation of spinopelvic alignment according to Roussouly classification can predict the occurrence of adjacent segment disease after lumbar fusion].

Objective: To investigate the correlation of spinopelvic alignment according to Roussouly classification on the occurrence of adjacent segment disease (ASD) in the patients undergoing fusion surgery for lumbar degenerative diseases. Methods: A cross-sectional study. Clinical data of 166 consecutive patients who had undergone lumbar fusion between January 2009 and January 2019 in the Affiliated Changzhou Second People's Hospital of Nanjing Medical University and Affiliated Drum Tower Hospital of Medical School of Nanjing University were retrospectively reviewed. There were 59 males and 107 females, with an average age of (58.6±9.5) years (ranged 41-78 years). Fusion length averagely spanned (1.7±0.7) levels (ranged 1-3 levels). The patients were classified by both "theoretical" (based on pelvic incidence (PI)) and "current"(based on sacral slope (SS)) Roussouly types. The patients were classified as "matched" if their "current" shape matched the "theoretical" type and otherwise as "unmatched". Multivariate logistic regression analysis of the variables recruited from univariate analyses was performed to identify the factors independently associated with the development of ASD after lumbar fusion. Results: The average follow-up duration after initial surgery was (49.2±20.7) months (ranged 25 to 134 months). Thirty (18.1%, 30/166) patients were diagnosed as ASD. Postoperatively, two thirds of the patients who suffered ASD after surgery were unmatched, while 36.8% (50/136) of the patients without ASD had unmatched type. Univariate analyses showed that older age, more fusion levels, float fusion, pre-and postoperative worse spinopelvic alignment, and postoperative unmatched Roussouly type were identified as risk factors of ASD. Multivariate logistic regression analysis identified postoperative Roussouly type mismatch (OR=3.310, 95%CI: 1.282-8.545, P=0.013), old age (OR=1.074, 95%CI: 1.019-1.131, P=0.008) and postoperative SS (OR=0.928, 95%CI: 0.865-0.995, P=0.036) as the independent risk factors of development of ASD after lumbar fusion. Conclusion: A significant association between postoperative sagittal malalignment and occurrence of ASD is detected, the evaluation of sagittal alignment by Roussouly classification could help predict the occurrence of ASD.

[Effects of colpotomic approaches on prognosis and recurrence sites of stage â a2-â ¡a2 cervical cancer after laparoscopic radical hysterectomy].

Objective: To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths. Methods: The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results: (1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer (P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage (HR=1.882, 95%CI: 1.305-2.716), LNM (HR=2.178, 95%CI: 1.483-3.200) and UCI (HR=3.650, 95%CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage (HR=2.500, 95%CI: 1.580-3.956), LNM (HR=2.053, 95%CI: 1.309-3.218), UCI (HR=3.984, 95%CI: 1.917-8.280), PVM (HR=3.235, 95%CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% (P=0.794), and the 5-year OS were 90.8% and 89.3% (P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions: Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

[Clinical efficacy observation of omalizumab on patients with moderate to severe allergic asthma for one year].

To observe the symptom control, pulmonary function changes and safety of use of omalizumab in patients with moderate to severe allergic asthma for 1 year. A small sample self-controlled study before and after treatment was conducted to retrospective analysis involved 17 patients with moderate to severe asthma who received omalizumab therapy for 12 months in Peking University People's Hospital and Beijing Jishuitan Hospital from January 2020 to December 2021. The clinical symptoms and pulmonary function changes were compared before treatment, after 6 months and 12 months of treatment, and the clinical data such as the use of other drugs and adverse reactions were observed. Statistical data are collected using the median method, and non-parametric paired Wilcoxon analysis was used for pairwise comparison. Before treatment with omalizumab, the patients' FeNO value was 79(58, 121) ppb, and the total serum IgE was 228(150.5, 345.5) IU/ml. After 6 months of omalizumab therapy, the percent predicted value of the forced expiratory volume in 1 second (FEV1%) before inhaled bronchodilator increased from 86.70(82.65, 91.35)% to 90.90(87.70, 95.85)% (Z=-3.626, P<0.001). The FEV1%pred after inhaled bronchodilator increased from 92.60(85.75, 96.90)% to 94.30(89.95, 98.15)% (Z=-2.178, P=0.029). The absolute value of improvement in FEV1 decreased from 150(95, 210)ml to 50(20, 125) ml (Z=-2.796, P=0.005), and the improvement rate decreased from 6.60(3.80, 7.85)% to 1.90(0.75, 4.85)% (Z=-2.922, P=0.003). After 12 months of treatment, the FEV1%pred before inhaled bronchodilator further increased to 92.90 (91.60, 98.15)% (Z=-3.575, -2.818, and P<0.001, 0.005 compared with before treatment and 6 months after treatment, respectively). The FEV1%pred after inhaled bronchodilator increased to 96.80 (91.90, 101.25)% (Z=-3.622, -1.638, and P<0.001, 0.008 compared with before treatment and after 6 months of treatment, respectively). The absolute value of improvement in FEV1 was 70 (35, 120) ml (P=0.004, 0.842 before treatment and 6 months after treatment, respectively), and the improvement rate was 3.0(1.0, 5.0)% (Z=-2.960, -0.166, and P=0.003, 0.868, compared with before treatment and after 6 months of treatment, respectively). After 12 months of treatment, ACT increased from 13 (10.5, 18) before treatment to 24 (23, 25) (Z=-3.626,P<0.001). Only 1 patient experienced an injection site skin reaction during treatment. Therefore, after 6 months and 12 months of treatment with omalizumab, the patient's lung function improved and symptoms were relieved, which could effectively prevent the acute exacerbation of asthma. Omalizumab treatment is safe and well tolerated, and no effect on blood pressure and blood glucose was observed.

Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer.

Damage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis. However, the detailed pathological mechanism remained deeply undetermined. In this case-control study, we screened the frequencies of mitochondrial tRNA (mt-tRNA) mutations in 80 breast cancer tissues and matched normal adjacent tissues. PCR and Sanger sequence revealed five possible pathogenic mutations: tRNAVal G1606A, tRNAIle A4300G, tRNASer(UCN) T7505C, tRNAGlu A14693G and tRNAThr G15927A. We noticed that these mutations resided at extremely conserved positions of tRNAs and would affect tRNAs transcription or modifications. Furthermore, functional analysis suggested that patients with these mt-tRNA mutations exhibited much lower levels of mtDNA copy number and ATP, as compared with controls (p<0.05). Therefore, it can be speculated that these mutations may impair mitochondrial protein synthesis and oxidative phosphorylation (OXPHOS) complexes, which caused mitochondrial dysfunctions that were involved in the breast carcinogenesis. Taken together, our data indicated that mutations in mt-tRNA were the important contributors to breast cancer, and mutational analyses of mt-tRNA genes were critical for prevention of breast cancer.

[Influencing factors of visual prognosis in patients with persistent submacular fluid after successful scleral buckle surgery for macula-off retinal detachment].

Objective: To investigate the factors influencing visual outcomes in patients with rhegmatogenous retinal detachment (RRD) who developed persistent submacular fluid (PSF) after scleral buckling surgery. Methods: A retrospective case series analysis was conducted. Clinical data were collected from patients who underwent successful scleral buckling surgery for RRD at Beijing Tongren Hospital from June 2020 to December 2022 and were followed up. Patients with RRD involving the macular area preoperatively and graded as C1 or below in proliferative vitreoretinopathy (PVR) were included. Surgical procedures followed a minimally invasive scleral buckling approach. PSF was defined as subretinal fluid persisting for more than 1 month postoperatively. Regular follow-up visits were scheduled at postoperative days 1, 3, 7, 2 weeks, and 1 month, followed by monthly visits until complete PSF absorption. Best-corrected visual acuity (BCVA), intraocular pressure, refractive error, slit-lamp biomicroscopy, binocular indirect ophthalmoscopy, and optical coherence tomography (OCT) were performed at each follow-up time point. Eyes were divided into two groups based on whether the final follow-up BCVA was≥0.5 and whether the absorption time of PSF was>6 months, and statistical analysis was performed using the Wilcoxon signed-rank test, chi-squared test, and Mann-Whitney U test. Results: A total of 46 patients (46 eyes) were included in this study, comprising 25 males and 21 females, with a median age of 32.5 (21.0, 57.3) years. The preoperative equivalent spherical refractive error was (-5.27±4.05) D, and the preoperative duration of illness was 30 (14, 92) days. The preoperative BCVA (logarithm of the minimum angle of resolution,logMAR) was 2.00 (1.00, 2.50). Scleral buckle surgery was performed in 28 eyes (60.9%), and 18 eyes (39.1%) underwent scleral buckle surgery combined with encircling. External drainage was performed in 15 eyes (32.6%), while 31 eyes (67.4%) had no external drainage. BCVA (logMAR) at 1 month, 3 months, and the final follow-up postoperatively was 0.60 (0.50, 1.00), 0.40 (0.28, 0.53), and 0.15 (0.00, 0.50), respectively. In the final follow-up, 31 eyes (67.4%) achieved BCVA≥0.5, and 26 eyes (56.5%) had continuous ellipsoid zone on OCT. The differences in BCVA (logMAR) between preoperative, 1 month, 3 months, and the final follow-up were statistically significant (Z=-5.85, -5.63, -4.73;all P<0.001). The absorption time of PSF postoperatively was 6.50 (3.00, 9.00) months, ranging from 2 to 19 months. The eyes with PSF duration<3 months, 3-6 months, and>6 months were 12 eyes (26.1%), 11 eyes (23.9%), and 23 eyes (50.0%), respectively. There were statistically significant differences between the two groups in preoperative BCVA≥0.05, preoperative duration of illness within 1 month, PVR grading, surgical method, and continuous ellipsoid zone on OCT (all P<0.05), while there were no statistically significant differences between the two groups in PSF absorption time, different types of PSF, and intraoperative drainage (all P>0.05). The PSF absorption time in the two groups was 7 (3, 10) months and 6 (4, 8) months, with no statistically significant difference (P>0.05). Conclusions: Preoperative visual acuity, duration of illness, and PVR grading are factors influencing visual outcomes in patients with RRD who have undergone scleral buckling surgery and develop PSF. In contrast, intraoperative drainage, PSF absorption time, and different PSF types are not factors affecting visual prognosis. Although PSF may persist for a long time after scleral buckling surgery, it does not significantly impact long-term visual outcomes.

[Research on early warning model of the hearing loss of workers exposed to noise].

Objective: To explore the change of hearing threshold of workers exposed to noise, establish an individual-based hearing loss early warning model, accurately and differentiated the health of workers exposed to noise. Methods: In September 2019, all physical examination data of 561 workers exposed to noise from an enterprise were collected since their employment. Three indicators of average hearing threshold of the better ear, namely, at high frequency, 4000 Hz and speech frequency, were constructed. The generalized estimating equation (GEE) was used to adjust gender and age and establish the warning model of each indicator. Finally, sensitive indicators and warning models were screened according to AUC and Yoden index. Results: Among the 561 workers exposed to noise, 26 (4.6%) workers had hearing loss. The sensitivity indicators were the average hearing threshold at speech frequency ≥20 dB, high frequency ≥30 dB and 4000 Hz ≥25 dB. The AUC of each index was 0.602, 0.794 and 0.804, and the Youden indexes were 0.204, 0.588 and 0.608, respectively. In GEE of hearing loss warning models, high-frequency hearing threshold ≥20 dB and 4000 Hz hearing threshold ≥25 dB were the optimal models, with AUC of 0.862. Conclusion: Combined with the changes of individual hearing threshold over the years, can accurately assess the risk of individual hearing loss of workers exposed to noise.