[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[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.

[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.

[Research progress in associations between dental caries and systemic diseases].

Dental caries is a bacteria-mediated, multifactorial, chronic progressive disease that results in the phasic demineralization and remineralization of dental hard tissues. In recent years, amounts of studies have focused on the association between dental caries and systemic diseases. This paper reviews the researches about associations between caries and systemic diseases. An electronic search was conducted in PubMed and Web of Science for articles published from 2003 to 2022 in the English language. Studies were included in the following ten categories of systemic diseases: cardiovascular diseases, metabolic disorders, respiratory diseases, autoimmune rheumatic diseases, neurologic diseases, gastrointestinal diseases, kidney diseases, skin diseases, iron deficiency anaemia and tumors. This review discusses the relationship between dental caries and systemic diseases, as well as the potentially involved mechanisms, providing new ideas for disease prevention, diagnosis, and treatment strategies for dentists and other clinicians.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[The efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy in children with allergic rhinitis during treatment].

Objective: To evaluate the efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic rhinitis (AR) during treatment. Methods: A total of 283 children with AR diagnosed with definite dust mite allergy and completed 2 to 3 years of SCIT who attended the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, from August 2019 to October 2021 were included, including 205 males and 78 females, with a mean age of 10.8 years. The total nasal symptoms score (TNSS), symptom medication score (SMS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS) before and after 2 to 3 years' treatment were recorded, and the differences before and after treatment were compared. Adverse reactions during SCIT were recorded to evaluate its safety. SPSS 22.0 software was used for statistical analysis. Results: The overall effectiveness rate during SCIT in 283 children with AR was 89.4% (253/283). Compared with baseline, all symptom scores, medication scores and quality of life scores were significantly lower after 2 to 3 years of SCIT (all P<0.05). Further group comparisons showed positive efficacy in patients with different clinical characteristics, including age, gender, smoking status, family history of AR, symptom severity, mono-or poly-allergy, and second immunization, with no statistically significant differences between groups (all P>0.05). A total of 12 735 injections were administered during the SCIT, and a total of 213 (1.67%) injections of local adverse reactions occurred, mainly in the initial treatment phase, and the diameter of the local air mass was mostly 5 to 20 mm; 71 (0.56%) injections of systemic adverse reactions occurred, mainly in the initial treatment phase, and most of them were grade 1 reactions with no serious systemic adverse reaction such as shock. Conclusion: Standardized dust mite SCIT has a good safety profile and definite efficacy in treating AR children with different clinical characteristics. It can significantly improve all symptoms, reduce the use of symptomatic drugs and improve their quality of life.

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.

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.

[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.

[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.

Intrinsic Capacity Impairment Patterns and their Associations with Unfavorable Medication Utilization: A Nationwide Population-Based Study of 37,993 Community-Dwelling Older Adults.

OBJECTIVES: Our aim was to explore the patterns of intrinsic capacity (IC) impairments among community-dwelling older adults and the associations of these different patterns with excessive polypharmacy, potentially inappropriate medications, and adverse drug reactions in a nationwide population-based study. DESIGN: A cross-sectional study included older adults from the Taiwan Integrated Care for Older People (ICOPE) program in 2020. SETTING AND PARTICIPANTS: The study subjects comprised 38,308 adults aged 65 years and older who participated in the ICOPE Step 1 screening and assessed six domains of IC following the World Health Organization (WHO) ICOPE approach. METHODS: Latent class analysis was adopted to identify distinct subgroups with different IC impairments patterns. The associations between different IC impairments patterns and unfavorable medication utilization, including excess polypharmacy (EPP), potentially inappropriate medications (PIMs), and adverse drug reactions (ADRs), were assessed by multivariate logistic regression models. RESULTS: Latent class analysis identified five distinct subgroups with different IC impairment patterns: robust (latent class prevalence: 59.4%), visual impairment (17.7%), physio-cognitive decline (PCD) with sensory impairment (12.3%), depression with cognitive impairment (7.7%), and impairments in all domains (2.9%). Compared to the robust group, all other groups were at higher odds for unfavorable medication utilization. The "depression with cognitive impairment" group (EPP: aOR=4.35, 95% CI 3.52-5.39, p<0.01; PIMs: aOR=2.73, 95% CI 2.46-3.02, p<0.01) and the "impairment in all domains" group (EPP: aOR=9.02, 95% CI 7.16-11.37, p<0.01; PIMs: aOR=3.75, 95% CI 3.24-4.34, p<0.01) remained at higher odds for EPP and PIMs after adjustment. CONCLUSIONS: We identified five distinct impairment patterns of IC, and each impairment pattern, particularly the "depression with cognitive impairment" and "impairment in all domains", was associated with higher odds of EPP and PIMs. Further longitudinal and intervention studies are needed to explore long-term outcomes of different impairment pattern and their reversibility.

[Changes in the structure of intestinal mucosal flora in colorectal cancer patients].

OBJECTIVE: To investigate the changes in bacterial flora in fecal samples, at the tumor loci and in adjacent mucosa in patients with colorectal cancer (CRC). METHODS: We collected fecal samples from 13 patients with CRC and 20 healthy individuals and tumor and adjacent mucosa samples from 6 CRC patients. The differences in bacterial composition between the fecal and mucosa samples were analyzed with 16S rDNA sequencing and bioinformatics methods. We also detected the total number of bacteria in the feces using flow cytometry, isolated and identified the microorganisms in the fecal and mucosa samples using common bacterial culture media. We further tested the effects of 7 isolated bacterial strains on apoptosis of 3 CRC cell lines using lactate dehydrogenase detection kit. RESULTS: The bacterial α-diversity in the feces of healthy individuals and in adjacent mucosa of CRC patients was significantly higher than that in the feces and tumor mucosa in CRC patients (P < 0.05). Lactobacillaceae is a specific bacteria in the feces, while Escherichia, Enterococcus, and Fusobacterium are specific bacteria in tumor mucosa of CRC patients as compared with healthy individuals. Cell experiment with3 CRC cell lines showed that Bacteroides fragilis isolated from the tumor mucosa of CRC patients produced significant inhibitory effects on cell proliferation (P < 0.0001), while the isolated strain Fusobacterium nucleatum obviously promoted the proliferation of the cell lines (P < 0.001). CONCLUSION: The bacterial flora in the feces, tumor mucosa and adjacent mucosa of CRC patients is significantly different from that in the feces of healthy individuals, and the fecal flora of CRC patients can not represent the specific flora of the tumor mucosa. Inhibition of F. nucleatum colonization in the tumor mucosa and promoting B. fragilis colonization may prove beneficial for CRC treatment.

[An in vitro model study of computer-guided endodontic microsurgery].

Objective: To assess and compare the accuracies and operating time of endodontic microsurgery performed by operators with different levels of experience in endodontics using computer-guided techniques including dynamic and static navigations in a surgical simulation model. Methods: Six pairs of three dimensional (3D)-printed models of upper and lower jaws were set up on dental manikins. A total of 120 teeth (10 teeth each jaw) were included in the models. Microsurgeries of osteotomy and root-resection were performed on the models by two operators with different experience, namely novices and experts, under of free hand (FH)(n=20), dynamic navigation (DN)(n=20), and static navigation (SN)(n=20) conditions, respectively. The duration of each operation was recorded. Cone-beam CT was taken for 3D-printed models before and after the operation. The path of preoperative surgery planning was simulated. The linear deviations at the entry and the end point and the angular deviation of the access path between the simulated and the actual operation were compared by the software. Results: Significant difference of the entry deviation was observed between the novices and the experts in the FH group [(1.44±0.49) and (1.02±0.58) mm] (q=4.67, P=0.020). There were no significant differences between the novices and the experts in the end point and angular deviations (P>0.05). For the novices, the entry deviations in both DN and SN groups [(0.76±0.32) and (0.66±0.20) mm] were significantly lower than those in FH group (q=7.58, P<0.001; q=8.66, P<0.001). The angular deviations in the abovementioned two groups (5.0°±3.5°, 3.9°±2.1°) were significantly lower than that in FH group (10.9°±6.1°) (q=7.38, P<0.001; q=8.70, P<0.001). For the experts, significant differences were found only in the angular deviations among DN, SN and FH groups (3.6°±1.9°, 3.2°±1.7° and 8.2°±3.9°) (q=5.74, P=0.001; q=6.29, P<0.001). The operation durations were significantly shortened for both the novices [(4.80±2.15), (1.09±0.48) min] (q=14.60, P<0.001; q=20.10, P<0.001) and the experts [(3.40±1.96),(1.02±0.34) min] (q=5.86, P<0.001; q=9.37, P<0.001) by using DN and SN techniques. Regarding the differences between tooth types, in FH group, the operating time on the anterior teeth was significantly shorter than that on the posterior teeth (q=8.14, P<0.001; q=5.20, P=0.007), while in DN and SN groups, there were no significant differences in the operating time between two tooth types (P>0.05). No significant differences were discovered in the accuracies on the anterior and posterior teeth among three techniques or between two kinds of operators (P>0.05). Conclusions: Dynamic and static navigation techniques could assist the clinicians, especially the novices, to improve the accuracies and shorten the operating time of osteotomy and root resection microsurgeries.

[Efficacy of Han-uvulopalatopharyngoplasty (HUPPP) combined with radiofrequency ablation of tongue base or HUPPP with traction of tongue base on moderate to severe patients with obstructive sleep apnea hypopnea syndrome (OSAHS):a multicenter randomized controlled trial].

Objective: To compare the therapeutic efficacy of Han-uvulopalatopharyngoplasty (HUPPP) combined with radiofrequency ablation of tongue base or HUPPP with traction of tongue base on moderate to severe patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: This is a multicenter randomized controlled trial. From March 2017 to July 2019, moderate to severe OSAHS patients from three clinical center in Shanghai who were intolerant to continuous positive airway pressure (CPAP) and with velopharyngeal and glossopharyngeal plane obstruction were enrolled in this study. According to the surgical type, they were 1∶1 randomized to HUPPP plus radiofrequency ablation of tongue base group (Ablation group) or HUPPP plus traction of tongue base group (Traction group). All patients completed over-night standard Polysomnography (PSG), upper-airway assessment (Friedman classification, Müller test, CT and cephalometric examination), preoperative routine examination, Epworth Sleepiness Scale (ESS) and Quebec sleep questionnaire (QSQ). Six to 12 months after operation, all the above-mentioned examinations were repeatedly performed. Changes of aforementioned variables before and after operation were assessed. Results: A total of 43 patients with moderate to severe OSAHS were enrolled in this study. One patient lost to follow-up, the remaining 21 were allocated to Ablation group and 21 were allocated to Traction group. The total therapeutic efficacy of all patients was 69.05% (61.90% in Ablation group and 76.19% in Traction group), but there was no statistical significance between the two groups (P= 0.317). The value of sleep scale score (ESS and QSQ), objective sleep variables (apnea-hypopnea index, oxygen saturation, percentage of time with blood oxygen less than 90% in total sleep time, oxygen desaturation index and micro-arousals) and upper airway cross-sectional area (palatopharyngeal and retrolingual area) of the two groups were improved (P<0.05), but the differences between the two groups were not statistically significant (P>0.05). Conclusion: For moderate to severe OSAHS who had glossopharyngeal plane obstruction, both HUPPP plus radiofrequency ablation of tongue base or HUPPP plus traction of tongue base are effective treatment for OSAHS, and the curative effect is similar. The choice of surgical type could be selected according to patient's or surgical conditions.

[Obstructive sleep apnea and metabolic syndrome: an association study based on a large sample clinical database].

Objective: To investigate the prevalence and associated risk factors of metabolic syndrome (MS) in patients with obstructive sleep apnea (OSA). Methods: From July 2007 to June 2017, a total of 8 155 adult subjects, including 6 484 males and 1 671 females, aged 18-90 (43.13±12.28), body mass index 14.61~59.56 (25.59±3.98) kg/m2,who were admitted to the Department of Otorhinolaryngology head and Neck surgery of The Sixth People's Hospital affiliated to Shanghai Jiao Tong University, were retrospectively analyzed. All patients underwent polysomnography and biochemical tests. Subjects were divided into four groups (non-OSA, mild OSA, moderate OSA, and severe OSA) according to OSA severity. The prevalence of MS was expressed as percentage, and the correlation between OSA and MS and its characteristic pathophysiological indicators was evaluated by logistic regression model after adjusting for factors such as gender, age, BMI, neck circumference, hip circumference, smoking and alcohol consumption, and was expressed by odds ratio (OR). SPSS 25.0 software was used for statistical analysis. Results: The overall prevalence of MS was 43.6%, and that of non-/mild/moderate/severe OSA group was 18.6%, 30.4%, 43.8%, 57.1%.Logistic regression showed that patients with mild/moderate/severe OSA had an increased risk of MS compared with non-OSA patients, with adjusted OR values and confidence intervals of 1.27 (1.05-1.54), 1.84 (1.53-2.22), and 2.08 (1.76-2.46), respectively (P<0.01).In addition, indicators of OSA anoxic burden [oxygen drop index(Toxygen=7.1), minimum blood oxygen(Tminimum=56.3), blood oxygen saturation below 90% cumulative time ratio (TCT90=10.6) ]were closely associated with MS disease(P<0.01), but sleep fragmentation index (arousals index) was not significantly associated with MS disease. Conclusion: The risk of MS gradually increases with the severity of OSA, and the indicators reflecting OSA hypoxia burden are closely related to MS disease.

[Characteristics of human papillomavirus infection and abnormal cervical cytology in health check-up females in Shenzhen].

Objective: To describe the characteristics of human papillomavirus infection and thinprep cytologic test (TCT) outcome in health check-up females in Shenzhen. Methods: Use cross-sectional design, collect information from data from health check-up females in Shenzhen and describe characteristics of HPV infections screening and TCT outcomes. Results: We collected the data of 75 754 females, 103 508 females and 69 964 females received HPV detection, TCT and combined detection respectively. HPV standardized infection rate was 19.89% (95%CI: 19.45%-20.33%) and showed a "U-shaped" pattern in age distribution. The most prevalent HPV genotypes were 52, 51, 16, 58 and 53. Infection rate was higher for high-risk HPV than low-risk HPV genotype. Single infection was more common than its multiple infection. In addition, 7.48% (95%CI: 7.22%-7.75%) women were TCT positive, of whom 4.58% (95%CI: 4.40%-4.76%), 2.54% (2.40%-2.69%), 0.27% (95%CI: 0.23%-0.31%) had atypical squamous cells, low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, respectively. Overall and subtype HPV infection rates increased with severity of abnormal cervical cytology. The most prevalent HPV genotypes were 52, 58 and 16 in women with abnormal cervical cytology. Conclusions: HPV prevalence remains at a high level in Shenzhen. This study suggests that attention should be paid to HPV screening, especially in young, perimenopausal women and in high risk HPV genotype infection. Timely follow-up and cervical cytology screening are required for women with high-risk HPV infection or persistent infection. Future vaccination strategies should take account of prevalent HPV genotype.

[The application of quantitative analysis of EBV DNA loads in plasma and peripheral blood mononuclear cells in Epstein-Barr Virus infection-related diseases in children].

Objective: To explore the correlation of EBV DNA load in two different types of plasma and peripheral blood mononuclear cells (PBMCs) in children with Epstein-Barr Virus (EBV) infection diseases. Methods: A retrospective evaluated was performed on EBV DNA quantification in plasma and PBMCs by qPCR between April, 2019 and December, 2020. The samples were collected from children of 456 cases with EBV infection and 2 306 healthy cases. In EBV infection group, boys were 253 and girls were 203, aged from 8 days to months to 16 years. In healthy group, boys were 1 267 and girls were 1 039, aged from 8 days to 16 years. Results: Infectious mononucleosis (IM) was the most common disease associated with EBV infection 73.68%(336/456). The detection rate of plasma and PBMCs in EBV infection group was 91.89% (419/456)and 99.34% (453/456)respectively, and was 100%(456/456) in plasma or PBMCs. The detection rate of plasma and PBMCs in healthy group was 1.13%(26/2 306) and 30.01%(715/2 306), respectively. Levels of EBV DNA in plasma and PBMCs in EBV infection group [IM, acute infections, pneumonia, post-transplantation lymphoproliferative disorder (PTLD), hemophagocytic lymphohistiocytosis, tonsillitis and lymphadenitis] was significantly higher than those in healthy group (In plasma, Z=-47.18,-34.41,-33.40,-31.71,-24.38,-20.86 and -20.59,respectively; In PBMCs, Z=-33.17,-16.45,-11.33,-9.45,-5.57,-5.16 and -5.45, respectively; P<0.05). In IM group, EBV DNA load in plasma and PBMCs in remission stage was significantly lower than those in infection stage (Z=-11.45, -8.53;P<0.05). In PTLD group, there was significant difference in EBV DNA load in plasma between infection and remission stage (Z=-4.13, P<0.05), while there was no significant difference in EBV DNA load in PBMCs (Z=-0.817, P>0.05). Conclusions: EBV infection was mainly caused by IM. Combined detection of plasma and PBMCs in EBV DNA is valuable for improving diagnosis ability of EBV infection-related diseases, and the load of EBV DNA could be used as a marker.

[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.