Effects of phenylephrine on systemic and cerebral circulations in humans: a systematic review with mechanistic explanations.

We conducted a systematic review of the literature reporting phenylephrine-induced changes in blood pressure, cardiac output, cerebral blood flow and cerebral tissue oxygen saturation as measured by near-infrared spectroscopy in humans. We used the proportion change of the group mean values reported by the original studies in our analysis. Phenylephrine elevates blood pressure whilst concurrently inducing a reduction in cardiac output. Furthermore, despite increasing cerebral blood flow, it decreases cerebral tissue oxygen saturation. The extent of phenylephrine's influence on cardiac output (r = -0.54 and p = 0.09 in awake humans; r = -0.55 and p = 0.007 in anaesthetised humans), cerebral blood flow (r = 0.65 and p = 0.002 in awake humans; r = 0.80 and p = 0.003 in anaesthetised humans) and cerebral tissue oxygen saturation (r = -0.72 and p = 0.03 in awake humans; r = -0.24 and p = 0.48 in anaesthetised humans) appears closely linked to the magnitude of phenylephrine-induced blood pressure changes. When comparing the effects of phenylephrine in awake and anaesthetised humans, we found no evidence of a significant difference in cardiac output, cerebral blood flow or cerebral tissue oxygen saturation. There was also no evidence of a significant difference in effect on systemic and cerebral circulations whether phenylephrine was given by bolus or infusion. We explore the underlying mechanisms driving the phenylephrine-induced cardiac output reduction, cerebral blood flow increase and cerebral tissue oxygen saturation decrease. Individualised treatment approaches, close monitoring and consideration of potential risks and benefits remain vital to the safe and effective use of phenylephrine in acute care.

[Classification of childhood arterial ischemic stroke].

The etiology of childhood arterial ischemic stroke is complex, and identifying the underlying cause is crucial for optimizing treatment and preventing recurrence. Currently, the classification methods for childhood arterial ischemic stroke are largely based on data from international studies, but a unified consensus have not yet been reached. This paper reviews the existing classification methods and their subtype definitions, and points out some doubts and ambiguities. On this basisi, combined with the data collected by Beijing Children's Hospital on Chinese children with arterial ischemic stroke, a new classification method (COIST) was proposed according to the etiology and pathogenesis, namely: inflammation (I), abnormal vascular structure (S), thrombophilia (T), heart disease (C), other identifiable causes (O), and uncertain causes; and various subtypes are listed. It is hoped that this new classification method can attract the attention and discussion of domestic colleagues, with the aim of further refinement, in order to help clinicians better understand and quickly identify the etiologies of childhood ischemic stroke.

[Application of modified urethral separation method in artificial urethral sphincter implantation and its influence on intraoperative urethral pressure profilometry].

Objective: To explore the application of modified urethral separation method in artificial urethral sphincter (AUS) implantation in patients with stress urinary incontinence (SUI), and its influence on the results of urethral pressure profilometry. Methods: A prospective collection of clinical data was conducted on 25 patients with stress urinary incontinence who underwent modified urethral separation method in AUS implantation and underwent urethral pressure profilometry in Beijing Hospital, Beijing Jishuitan Hospital Affiliated to Capital Medical University and the Second Hospital Affiliated to Tianjin Medical University from March 2019 to June 2023. The improved urethral separation method was to borrow part of the white membrane tissue of the cavernous body while freeing the dorsal side of the cavernous body of the urethra. The circumference of the urethra, sleeve size, and urethral pressure were recorded, the patient's autonomous urinary control before and after surgery and the changes of the international consultation on incontinence questionnaire-short form (ICI-Q-SF) score, incontinence quality of life questionnaire (I-QoL) score, urinary frequency score, nocturia score were compared. Follow-up was conducted in the clinic or by telephone at 1, 3, 6, and 12 months after activation of the device, and once a year thereafter. Local skin status and urine control were assessed, residual urine volume was measured by ultrasound and subjective score scale was completed. Results: All patients were male, aged 27-85 (65.8±15.7) years old. The circumference of the cuff used in this study was 4.0 cm in 4 patients (16.0%), 4.5 cm in 16 patients (64.0%), 5.0 cm in 4 patients (16.0%), and 5.5 cm in 1 patient (4.0%). Among them, the urethral circumference matched the cuff size in 14 cases (56.0%), the urethral circumference was smaller than the cuff size in 4 cases (16.0%), and the urethral circumference was larger than the cuff size in 7 cases (28.0%). Preoperative urodynamic examination showed that the maximum urethral pressure (MUP) was (78.0±25.9) cmH2O, (1 cmH2O=0.098 kPa) and the maximum urethral closure pressure (MUCP) was (53.4±26.6) cmH2O. The MUP of AUS device in the inactivated state was (88.0±26.5) cmH2O, which was not significantly higher than that before operation (P>0.05). The MUCP was (68.2±24.5) cmH2O, which was significantly higher than that before operation (P<0.05). The MUP and MUCP of the AUS device in the activated state were (146.6±25.2) cmH2O and (123.0±28.3) cmH2O, which were significantly higher than those before surgery and in the inactivated state (both P<0.001). All patients in the group reached the social urinary control standards at the first month of device activation. During a follow-up period of 2-50 months, 22 patients (88.0%) used the initial AUS device and all met social urinary control standards. The AUS device was replaced in 1 case. One patient died of cerebrovascular accident. One patient removed the device due to complications. The number of pads [M (Q1, Q3)] used in 25 patients before and after operation was 4.5 (3.0, 6.5) and 1 (0, 1) respectively, with statistically significant differences (P<0.001). ICI-Q-SF score, I-QoL score, urinary frequency score and nocturia score of 25 patients were significantly improved after surgery (all P<0.05). The incidence of postoperative complications was 20.0% (5/25), including 2 cases of painless hematuria, 1 case of infection, 1 case of urethral erosion, and 1 case of dysuria. Except for one patient who experienced urethral erosion and had his sleeve removed, the remaining four patients regained social urination control with active support treatment, and no symptoms recurred until the last follow-up. Conclusion: The modified urethral separation method has no significant effect on urethral pressure in patients with SUI, and can increase the volume of peri-urethral tissue in the cuff, thereby reducing the risk of intraoperative urethral injury and the incidence of postoperative urethral erosion.

[Gastrointestinal tumors with SWI/SNF complex deficiency: a clinicopathological analysis of 36 cases].

Objective: To investigate the clinicopathological characteristics of gastrointestinal tumors with SWI/SNF complex deficiency and to perform a prognostic analysis of the patients. Methods: Gastrointestinal tumor cases with SWI/SNF complex deficiency expression diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from August 2021 to May 2023 were collected. Hematoxylin and eosin (HE) stained slides were reviewed, and immunohistochemical results were analyzed. Clinical and pathological information was recorded, and relevant literature was reviewed. Results: A total of 36 cases of gastrointestinal tumor with loss of SWI/SNF complex expression were identified, including 28 males (77.8%) and 8 females (22.2%). The average age at diagnosis was 70 years (range 48-85 years). Clinical staging showed 3 cases in stage Ⅰ (8.3%), 12 cases in stage Ⅱ (33.3%), 19 cases in stage Ⅲ (52.8%), and 2 cases in stage Ⅳ (5.6%). Complete or partial loss of ARID1A expression was observed in 20 cases (55.6%); complete or partial loss of SMARCA2 expression was observed in 24 cases (66.7%). SMARCA4 exhibited complete loss of expression in 4 cases (11.1%). Eleven cases (30.6%) showed concurrent complete or partial losses of both ARID1A and SMARCA2 expression. Twelve cases (33.3%) had mismatch repair protein deficiency, all of which were characterized by MLH1/PMS2 absence. Mismatch repair protein deficiency was associated with loss of ARID1A expression (P<0.01). Patients with mismatch repair protein deficiency were also associated with earlier clinical stage and a lower risk of lymph node metastasis compared to the ones with intact mismatch repair proteins (P<0.05). Conclusions: SWI/SNF complex deficiency in gastrointestinal tumors is associated with dedifferentiation and often accompanied by mismatch repair protein deficiency. Compared to the cases with intact mismatch repair proteins, the cases with defective mismatch repair protein have an earlier clinical stage and a lower risk of lymph node metastasis.

Functional analysis of rare anti-Müllerian hormone protein-altering variants identified in women with PCOS.

Recently, rare heterozygous AMH protein-altering variants were identified in women with polycystic ovary syndrome (PCOS), causing reduced anti-Müllerian hormone (AMH) signaling. However, the exact functional mechanism remains unknown. Here, we analyzed the processing, secretion, and signaling of these AMH variants. Functional analysis of six PCOS-specific AMH variants (V12G, P151S, P270S, P352S, P362S, H506Q) and one control-specific variant (A519V) was performed in the mouse granulosa cell-line KK-1. Human (h) AMH-151S and hAMH-506Q have ∼90% decreased AMH signaling compared to wild-type (wt) AMH signaling. Coexpression of hAMH-151S or hAMH-506Q with wt-hAMH dose-dependently inhibited wt-hAMH signaling. Western blotting revealed that hAMH-151S and hAMH-506Q proteins were detected in the cell lysate but not in the supernatant. Confocal microscopy showed that HEK293 cells expressing hAMH-151S and hAMH-506Q had higher cellular AMH protein levels with endoplasmic reticulum (ER) retention compared to cells expressing wt-hAMH. Using two AMH ELISA kits, hAMH-151S was detected in the cell lysate, while only very low levels were detected in the supernatant. Both hAMH-362S and hAMH-519V were detectable using the automated AMH ELISA but showed severely reduced immunoactivity in the manual ELISA. Surprisingly, hAMH-506Q was undetectable in both the cell lysate and supernatant using either ELISA. However, in PCOS cases, heterozygous carriers of the P151S and H506Q variants still had detectable AMH in both assays. Thus, P151S and H506Q disrupt normal processing and secretion of AMH, causing ER retention. Additionally, AMH variants can impair the AMH immunoactivity. An AMH variant may be considered when serum AMH levels are relatively low in PCOS cases.

Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.

Feature pyramid network-based computer-aided detection and monitoring treatment response of brain metastases on contrast-enhanced MRI.

AIM: To investigate the value of feature pyramid network (FPN)-based computer-aided detection (CAD) of brain metastases (BMs) before and after non-surgical treatment, and to evaluate its performance in monitoring treatment response of BM on contrast-enhanced (CE) magnetic resonance imaging (MRI). MATERIAL AND METHODS: Eighty-five cancer patients newly diagnosed with BM who had undergone initial and follow-up three-dimensional (3D) CE MRI at Liaocheng People's Hospital were included retrospectively in this study. Manual detection (MD) was performed by reviewer 1. Computer-aided detection (CAD) was performed by reviewer 2 using uAI Discover-BMs software. The treatment response was assessed by the two reviewers for each patient separately. A paired chi-square test was used to compare the differences in the detection of BM between MD and CAD. Agreement between MD and CAD in monitoring treatment response was assessed by kappa test. RESULTS: The sensitivities of MD and CAD on initial 3D CE MRI were 78.65% and 99.13%, respectively. The sensitivities of MD and CAD on follow-up 3D CE MRI were 76.32% and 98.24%, respectively. There was a very good agreement between Reviewer 1 and Reviewer 2 in evaluating the treatment response of BM. CONCLUSION: FPN-based CAD has a higher sensitivity of close to 100% and lower false negatives (FNs) for BM detection, compared to MD. Although CAD had a few shortcomings in reflecting changes of BMs after treatment, it had high performance in monitoring treatment response of BM on CE MRI.

[Comparison of three methods for establishing rat peri-implantitis model].

OBJECTIVE: To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods. METHODS: Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1ß (IL-1ß). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death. RESULTS: After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1ß in the test groups were higher than those in the control group (P < 0.05). CONCLUSION: Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

[Clinical characteristics and therapeutic effectiveness of post craniotomy cervicogenic headache].

From January 2019 to December 2021, the clinical data of 151 patients with post craniotomy cervicogenic headache from Beijing Tiantan Hospital affiliated to Capital Medical University were retrospectively collected. The characteristics of cervicogenic headache were summarized, the numerical rating score (NRS) of patients before and after treatment of compound opioids and/or cervical nerve block was compared, and the occurrence of related adverse reactions and complications was counted. The onset of cervicogenic headache in 151 patients was on the (5.5±2.0) d after craniotomy, of which 131 (86.8%) had unilateral pain, pain in 127 (84.1%) could be induced by cervical activity, and 118 (78.1%) had limited neck movement. Of the 124 patients treated with compound capsule of oxycodone and acetaminophen, 85 (68.5%) patients had an NRS of (8.01±0.82) before treatment and 2.0 (1.0, 3.0) after treatment (P<0.001). Thirty-nine patients who did not respond to medical therapy received cervical nerve block, and the NRS scores before and after receiving the nerve block were (7.49±1.12) and 2.0 (1.0, 2.5), respectively, with a statistically significant difference (P<0.001). Twenty-seven patients who received cervical nerve block without medical treatment, and the NRS before and after treatment was (9.0±0.9) and 1.0 (1.0, 3.0), respectively, with a statistically significant difference (P<0.001). Among the 124 patients receiving medication, 14 (11.3%) developed mild dizziness and nausea, which were resolved after stopping the drug, and no other drug-related adverse reactions were found. None of the patients who received nerve blocks saw complications associated with nerve block procedures. Compound capsule of oxycodone and acetaminophen are effective for most of patients with post craniotomy cervicogenic headache. Cervical nerve block is effective and safe for patients with or without drug resistance.

Total and free vitamin D metabolites in patients with primary hyperparathyroidism.

PURPOSE: To evaluate total and free vitamin D metabolites and hormone-to-prohormone [1,25(OH)2D/25(OH)D] "activation ratio" in PHPT patients with low or insufficient vitamin D status. METHODS: Thirty female patients with primary hyperparathyroidism (PHPT) and 30 age and body mass index (BMI) matched healthy controls were enrolled. Serum levels of calcium, intact parathyroid hormone (iPTH), vitamin D binding protein (DBP), albumin, total 25(OH)D and 1,25(OH)2D were measured. The activation ratio of vitamin D was calculated as total 1,25(OH)2D/25(OH)D. Calculated serum-free 25(OH)D and 1,25(OH)2D levels were also reported. RESULTS: Compared to the control subject, patients with PHPT had a lower total 25(OH)D and DBP levels (p < 0.001). The serum concentration of free 25(OH)D and total 1,25(OH)2D were similar between the two groups; but free 1,25(OH)2D levels were about 26% higher in the PHPT patients compared to controls (p < 0.001). PHPT patients had a significantly higher activation ratio (p < 0.01), although their total 25(OH)D were lower than controls. The free (but not total) 1,25(OH)2D level was inversely correlated with DBP (p < 0.01). Both free 1,25(OH)2D levels and activation ratio were positively correlated with iPTH and calcium levels (p < 0.01). The activation ratio was highly correlated with levels of total vitamin D stores and free vitamin D metabolites (p < 0.001). CONCLUSION: Patients with PHPT had significantly higher free 1,25(OH)2D levels and activation ratio compared to control subjects. We suggest that levels of free vitamin D metabolites and vitamin D activation ratio may provide additional values for the diagnosis and therapeutic choices in these patient populations with compromised vitamin D status.

Regulatory role of phosphoproteins in the development of bovine small intestine during early life.

The small intestine is the primary site of nutrient digestion and absorption, which plays a key role in the survival of neonatal calves. A comprehensive assessment of the phosphoproteomic changes in the small intestine of neonatal calves is unavailable; therefore, we used phosphopeptide enrichment coupled with liquid chromatography-tandem mass spectrometry to investigate the changes in the phosphoproteome profile in the bovine small intestine during the first 36 h of life. Twelve neonatal male calves were assigned to one of the following groups: (1) calves not fed colostrum and slaughtered approximately 2 h postpartum (n = 3), (2) calves fed colostrum at 1 to 2 h and slaughtered 8 h postpartum (n = 3), (3) calves fed 2 colostrum meals (at 1-2 and 10-12 h) and slaughtered 24 h postpartum (n = 3), (4) calves fed 3 colostrum meals (at 1-2, 10-12, and 22-24 h) and slaughtered 36 h postpartum (n = 3). Mid-duodenal, jejunal, and ileal samples of the calves were collected after slaughter. We identified 1,678 phosphoproteins with approximately 3,080 phosphosites, which were mainly Ser (89.9%), Thr (9.8%), and Tyr (0.3%) residues; they belonged to the prodirected (52.9%), basic (20.4%), acidic (16.6%), and Tyr-directed (1.7%) motif categories. The regional differentially expressed phosphoproteins included zonula occludens 2, sorting nexin 12, and protein kinase C, which are mainly associated with developmental processes, intracellular transport, vesicle-mediated transport, and immune system process. They are enriched in the endocytosis, tight junction, insulin signaling, and focal adhesion pathways. The temporal differentially expressed phosphoproteins included occludin, epsin 1, and bridging integrator 1, which were mainly associated with macromolecule metabolic process, cell adhesion, and growth. They were enriched in the spliceosomes, adherens junctions, and tight junctions. The observed changes in the phosphoproteins in the tissues of small intestine suggest the protein phosphorylation plays an important role in nutrient transport and immune response of calves during early life, which needs to be confirmed in a larger study.

[The applications and challenges of liquid chromatography tandem mass spectrometry in maternal and child health].

Due to its ultra-high sensitivity, specificity and throughput, liquid chromatography tandem mass spectrometry (LC-MS/MS) has become an important analytical tool in clinical laboratories in quantifying various small molecules, such as vitamins, bile acids, steroids and other internal metabolites relevant to maternal diseases. As an effective means of screening and diagnosing diseases in preventive medicine, LC-MS/MS has been widely used in maternal and child health, contributing to the reduction of the incidence of maternal and child diseases and premature morbidity and mortality. At present, LC-MS/MS is an emerging and powerful platform in laboratory testing in China, facing both challenges and opportunities. In this article, the representative applications in the field of maternal and child health are summarized and discussed, along with the major hurdles of LC-MS/MS in clinical recognition and implementation.

[Clinicopathological characteristics of anti-PD-1 associated gastroenteritis].

Objective: To investigate the clinicopathological features of anti-PD-1 related gastroenteritis, understand and recognize the disease, and avoid misdiagnoses. Methods: Three cases of anti-PD-1 related gastroenteritis diagnosed and treated at the Zhongshan Hospital Affiliated to Fudan University, Shanghai, China from 2020 to 2021 were collected. The clinical and pathological features were analyzed and the patients were followed up by telephone. Results: The three patients were all male and aged 63, 39 and 73 years, respectively. They had previously developed gastrointestinal symptoms as a result of immunotherapy for a malignant tumor. Endoscopically, 2 patients presented with pancolitis, and 1 patient presented with a large antral ulcer involving the pyloric canal in the stomach. Histologically, there were marked atrophy and thinning of the epithelium, diffuse infiltration of numerous neutrophils in the lamina propria, formation of micro-abscesses in the crypt/glandular lumen, structural changes (branching and distortion) of the glands, and significant glandular dilatation. In addition, chronic inflammatory features (e.g., lymphoplasmacytosis) were focally seen in 2 cases. Cytomegalovirus immunohistochemical stains were negative in all 3 cases. Based on the history and morphology, all 3 cases were diagnosed as anti-PD-1 related gastroenteritis. According to the above diagnosis, the treatment for all 3 patients was to stop anti-PD-1 therapy and use corticosteroids. Clinical follow-up was conducted. The gastrointestinal symptoms of all 3 patients improved significantly and diarrhea symptoms were relieved after stopping immunotherapy. Conclusions: Anti-PD-1 related gastroenteritis is not rare, but pathologists may lack sufficient understanding of it. Combined with clinical history and pathologic characteristics of the lesion, pathologists should consider this disease to avoid the misdiagnoses and missed diagnoses.

[Tuberculosis screening in respiratory department inpatients in comprehensive medical institutions].

Objective: To explore the effect of screening tuberculosis patients in the respiratory department of general hospitals, and to provide a basis for the development of patient screening strategy. Methods: Clinical information and sputum samples of inpatients in the respiratory department of a general hospital in Longhua District, Shenzhen from December 2018 to December 2020 were collected. Sputum samples were sent to the tuberculosis laboratory of the Shenzhen Longhua Center for Chronic Disease Control (designated tuberculosis diagnosis and treatment institution) for sputum smear, liquid culture and Gene-Xpert test. Results: A total of 407 sputum samples (23 cases of suspected tuberculosis by chest imaging and 384 by clinical manifestations) were collected from 3 724 hospitalized patients. A total of 88 patients with positive etiology were detected by the three methods, and the positive rate was 21.6% (88/407), among which 15 patients with suspected tuberculosis were detected by imaging reports, and the positive rate of etiology was 19.0% (73/384) in the reported patients without imaging reports. At least 1.96% (73/3 724) of the hospitalized patients were estimated to be tuberculosis positive during the study. Pneumonia (30.1%,22/73), cough (15.1%,11/73) and pulmonary infection (15.1%,11/73) were the main characteristics in the patients with positive pathogens. Conclusions: Screening for tuberculosis among inpatients in the respiratory department of general hospitals is an effective way to detect patients who were radiographically reported to have probable tuberculosis. It is of great significance to carry out active screening in key departments of general hospitals for tuberculosis detection and control.

Study of pharyngeal airway morphology with CBCT: Benefits of four premolar extraction orthodontic treatments.

Background and Aim: Four premolars extractions are routine procedures for correction of malocclusion, but will inevitably lead to a reduction of tongue space, whether this will weaken the pharyngeal airway remains a controversy. Patients and Methods: Cone-beam computed tomography (CBCT) radiographs of 80 patients who completed four premolar extraction orthodontic treatments were collected and divided into three anteroposterior skeletal groups according to the ANB (angle subspinale to nasion to supramentale) value. Linear, angular, cross-sectional area, and volumetric dimensions of the pharyngeal airway were measured using Dolphin Imaging 11.9 software. One-way analysis of variance and Pearson's correlation coefficient test were performed to assess the intergroup comparisons. Treatment changes were evaluated with two-sample t-tests. Results: In intergroup comparisons, vertical linear and cross-sectional area differences were identified in S-Go/N-Me, VD1, VD1/N-Me, VD2/N-Me, AA, OAA and OMINI (p<0.05), while other measurements showed no significant differences. Angle2, the tilting degree of the pharyngeal airway, showed a positive correlation with ANB (p<0.05). As for the treatment changes, a significant increase was found in the pharyngeal airway in the Class I group (OUA p<0.05, VD1 p<0.001, VD2 p<0.05) and Class II group (VD1 p<0.001. VD2, p<0.05), and inversely, a significant decrease was found in the pharyngeal airway in the Class III group (OAA p<0.05, OMINI p<0.05, OUA p<0.05). No volumetric difference was identified. Interestingly, regarding the preoperative pharyngeal airway size, values trended to the mean value significantly. Conclusion: Four premolar extraction orthodontic treatments did not affect the pharyngeal airway volume except for the vertical liner and cross-sectional area dimensions. The trend of the gold standard suggested a positive influence of four premolar extraction orthodontic treatments.

Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect.

OBJECTIVE: To evaluate comprehensively, using chromosomal microarray analysis (CMA) and exome sequencing (ES), the prevalence of chromosomal abnormalities and sequence variants in unselected fetuses with congenital heart defect (CHD) and to evaluate the potential diagnostic yields of CMA and ES for different CHD subgroups. METHODS: This was a study of 360 unselected singleton fetuses with CHD detected by echocardiography, referred to our department for genetic testing between February 2018 and December 2019. We performed CMA, as a routine test for aneuploidy and copy number variations (CNV), and then, in cases without aneuploidy or pathogenic CNV on CMA, we performed ES. RESULTS: Overall, positive genetic diagnoses were made in 84 (23.3%) fetuses: chromosomal abnormalities were detected by CMA in 60 (16.7%) and sequence variants were detected by ES in a further 24 (6.7%) cases. The detection rate of pathogenic and likely pathogenic genetic variants in fetuses with non-isolated CHD (32/83, 38.6%) was significantly higher than that in fetuses with isolated CHD (52/277, 18.8%) (P < 0.001), this difference being due mainly to the difference in frequency of aneuploidy between the two groups. The prevalence of a genetic defect was highest in fetuses with an atrioventricular septal defect (36.8%), ventricular septal defect with or without atrial septal defect (28.4%), conotruncal defect (22.2%) or right ventricular outflow tract obstruction (20.0%). We also identified two novel missense mutations (c.2447G>C, p.Arg816Pro; c.1171C>T, p.Arg391Cys) and a new phenotype caused by variants in PLD1. CONCLUSIONS: Chromosomal abnormalities were identified in 16.7% and sequence variants in a further 6.7% of fetuses with CHD. ES should be offered to all pregnant women with a CHD fetus without chromosomal abnormality or pathogenic CNV identified by CMA, regardless of whether the CHD is isolated. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

[The exposure of antibiotics on the eradication of bismuth quadruple therapy in H.pylori infection].

Objective: To analyze the impact of previous exposure to macrolide, quinolones and nitroimidazole antibiotics on eradication rate of bismuth quadruple therapy (BQT) in newly diagnosed patients with Helicobacter pylori(H. pylori). Methods: A total of 469 patients with H. pylori initially treated at the Third Hospital of Peking University from September 2017 to August 2020 were retrospectively recruited. The therapeutic regimens were BQT containing clarithromycin/levofloxacin/metronidazole recommended by Chinese guidelines. Clinical data were collected, including general demographic data, exposure history of antibiotics, CYP2C16 metabolic pattern, endoscopic diagnosis, bacterial density, H.pylori resistance, eradication results, etc. Univariate analysis, Chi-square test, Fisher exact probability test, Kruskal-Wallis H test and Logistic regression model were used as statistical methods. Results: Among different eradication therapies, univariate and multivariate analyses suggested that previous exposure to macrolides (OR=3.37,95%CI 1.04-10.98, P<0.05) was relevant to the decreased eradication rate of BQT containing clarithromycin. This may be due to increased resistance to clarithromycin (OR=6.12,95%CI 3.99-9.40, P<0.01).The previous exposure to quinolones (OR=3.65, 95%CI 1.27-10.49, P<0.05) was relevant to the decreased eradication rate of BQT containing levofloxacin, which was probably explained by the increased resistance to levofloxacin (OR=2.50, 95%CI 1.69-3.71, P<0.01). But the previous history of nitroimidazole did not impact the efficacy of BQT containing metronidazole. Conclusions: In patients newly diagnosed with H.pylori infection, the previous exposure to macrolide or quinolones antibiotics is related to lower eradiation rates of H. pylori. Although the exposure to nitroimidazole also indicates drug resistance to metronidazole, the clinical efficacy of BQT with metronidazole 400 mg four times a day is not affected.

[Management algorithm for septic arthritis after anterior cruciate ligament reconstruction].

OBJECTIVE: To summarize the experience in the diagnosis and management of septic arthritis after anterior cruciate ligament reconstruction. METHODS: A retrospective review was conducted of all the arthroscopic anterior cruciate ligament reconstructions performed at Department of Sports Medicine, Peking University Third Hospital between January 2001 and December 2020. In the study, 65 of 27 867 patients experienced postoperative septic arthritis. The incidence, presentation, laboratory results, treatment, and outcome of all the infected patients were analyzed. The experiences of diagnosis and management of septic arthritis after anterior cruciate ligament reconstruction were summarized. RESULTS: A total of 27 867 anterior cruciate ligament reconstructions were performed at our department between January 2001 and December 2020. In the study, 65 (0.23%) patients were identified with postoperative septic arthritis. The most common symptoms of the infected patients were fever (38.7±0.5) ℃, knee swelling, pain, and restricted motion. The mean peripheral white blood cell count (WBC) was (9.2±2.6)×109/L (range 4.2×109/L-19.4×109/L), with (72.5±6.3) % (range 54.9%-85.1%) polymorphonuclear neutrophils (N). The mean erythrocyte sedimentation rate (ESR) was (59.9±24.1) mm/h (range 9-108 mm/h), C-reactive protein (CRP) was (10.9±5.7) mg/dL (range 1.2-30.8 mg/dL), and fibrinogen (FIB) level was (7.0±1.6) g/L (range 3.7-10.8 g/L). All of the laboratory results were statistically higher in the infection group compared with the normal postoperative group (P＜0.001). The synovial white blood cell count (SWBC) of aspirated knee joint fluid was (45.0±29.8)×109/L (range 7.1×109-76.5×109/L). Polymorphonuclear cell percentage (PMNC) was (90.27±7.86) % (range 60%-97%). In the study, 45 patients (69.2%) had positive aspirate cultures. Microbiology showed coagulase-negative Staphylococcus (CNS) and Staphylococcus aureus (SA) were the most common bacterium (34 cases and 7 cases, individually). There were 26 methicillin-resistant Staphylococcus. Both conservative (16 patients) and operative (49 patients) treatments were effective, but conservative group had a longer recovery time (5.6 d vs. 1.6 d, P=0.042). CONCLUSION: Septic arthritis after arthroscopic anterior cruciate ligament reconstruction is a rare but potentially devastating complication. The correct diagnosis relies on synovial fluid analysis and bacterial culture. Our proposed treatment protocol is arthroscopic debridement and antibiotic therapy as quickly as possible.

[Quality of life and related factors in patients with interstitial cystitis/bladder pain syndrome].

OBJECTIVE: To evaluate the quality of life of patients with interstitial cystitis/bladder pain syndrome (IC/BPS), to compare the difference between IC/BPS and overactive bladder (OAB) pain syndrome, and to explore the related factors affecting the quality of life of IC/BPS patients. METHODS: The demographic data of female outpatients with IC/BPS in Beijing Hospital and other medical centers in China were collected. The quality of life of the patients was investigated by multi-angle questionnaires and compared with the data of OAB patients. According to the influence degree of quality of life, the patients with IC/BPS were divided into mild-moderate group and severe group. RESULTS: In this study, 109 patients with IC/BPS were included. The average age was (46.4±14.3) years and the average course of disease was (39.4±51.6) months. Compared with the OAB patients, the patients in IC/BPS group had a longer average course of disease (P=0.008), a lower proportion of the patients of first visit for the disease (P < 0.001), a higher score of the American Urological Association symptom index (AUA-SI) (P < 0.001), a lower body mass index (BMI) ratio (P=0.016), and a lower incidence of constipation (P=0.006). IC/BPS had the greatest impact on family life, followed by social activity. The score of IC/BPS related symptoms on family life was significantly higher than that of the OAB group (P=0.003). The top three symptoms of the IC/BPS patients were pain (45%), frequency (28%) and urgency (17%). The score of quality of life in the IC/BPS patients was significantly higher than that in the OAB patients (P < 0.001). Caffeine intake (P=0.034) and constipation (P=0.003) might be the factors influencing the quality of life of the patients with IC/BPS. CONCLUSION: IC/BPS has a great influence on the quality of life of patients. Caffeine intake and constipation may be related factors affecting the quality of life of patients with IC/BPS. Urologists should recommend changes in diet and lifestyle to reduce symptoms and improve the patients' quality of life.

[Factors affecting intraoperative changes in regional cerebral tissue oxygen saturation in elderly patients undergoing laparoscopic hysterectomy].

Objective: To explore the factors that affect the fluctuation of intraoperative regional cerebral oxygen saturation (rSctO2) in elderly patients undergoing laparoscopic hysterectomy. Methods: A retrospective analysis of 39 elderly patients undergoing elective laparoscopic hysterectomy in Yale New Haven Hospital from October 2016 to February 2017 was performed. Factors including patients' demographic data, past medical history, intraoperative monitoring index and rSctO2 index (baseline, maximum, minimum, maximum-baseline, baseline-minimum) were recorded. Pearson correlation analysis was used to analyze the correlation between rSctO2 indexes and preoperative and intraoperative factors. Independent sample t-test was used to compare the differences of rSctO2 indexes between hypertension group and the group without hypertension, as well as diabetes group and the group without diabetes. Taking diabetes as the stratification factor, the relationship between rSctO2and factors including age, body mass index, hypertension were analyzed using multivariate analysis. Results: The age of the patients was (67.6±5.6) years old. The baseline value of rSctO2 was (71.2±3.9)% in the left frontal lobe and (70.8±4.1)% in the right frontal lobe. Results from univariate analysis showed that the left and right maximum-baseline value of rSctO2 were (12.9±4.5)% and (12.8±4.4)%, which were significantly lower than (16.3±4.2)% and (16.2±4.9)% in the group without hypertension (t=2.329, 2.266, all P<0.05). The right baseline-minimum in the group with hypertension was (5.3±3.7)%, which was significantly higher than (2.7±4.2)% in the group without hypertension (t=-2.061, P<0.05). The left minimum value of rSctO2 in diabetic group was (64.4±4.2)%, and the maximum value of rSctO2on the left and right sides were (81.7±4.0)% and (81.9±4.5)%, which were lower than (68.4±4.1)%, (86.7±4.2)% and (86.0±3.7)% in the group without diabetes (t=2.623, 3.297, 2.850, all P<0.05). The results of multivariate analysis showed the influence of age (t=2.866, P<0.05) and hypertension on left maximum-baseline (t=-4.530, P<0.01) was statistically significant. The influence of hypertension on right maximum-baseline was statistically significant (t=-4.629,P<0.01). Conclusion: Preoperative diabetes and hypertension are factors significantly affecting the intraoperative rSctO2 of elderly patients with laparoscopic hysterectomy.