[Detection of cytogenetic abnormalities in multiple myeloma by using optical genome mapping].

Multiple myeloma (MM) is a plasma cell neoplasm characterized by numerous chromosomal number and structural abnormalities, which are of great significance for risk stratification and response evaluation of MM patients. Optical genome mapping (OGM) is a novel technology that has the potential to resolve many of the issues and limitations associated with traditional cytogenetic methods. To date, the clinical utility of OGM has been validated in the fields of cancer, reproduction, and embryonic dysplasia, et al. In this study, we compared OGM to traditional techniques for the first time in five newly diagnosed MM patients, and evaluated the potential of OGM for detecting cytogenetic aberrations and its clinical application value in MM.

Impact of preoperative balance training on postoperative functional recovery of patients after total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Previous studies' results on the impact of preoperative balance training on postoperative functional recovery after total knee arthroplasty (TKA) appeared to be ambiguous. Thus, this systematic review and meta-analysis were performed to investigate the effects of preoperative balance training on walking ability, balance-specific performance, and other functional indicators in elderly patients post-TKA. MATERIALS AND METHODS: Patient data were obtained from databases including PubMed, Physiotherapy Evidence Database (PEDro), CINAHL, SPORTDiscus, and Scopus. The inclusion criteria followed the Population-Intervention-Comparison-Outcome (PICO) principle. The assessment process involved meticulous screening, judicious data extraction, and rigorous evaluation of trial method quality, conducted by two independent researchers. Based on standardized mean differences and 95% confidence intervals, meta-analysis was performed employing a random-effects model or fixed-effects model. RESULTS: Preoperative balance training appears to be a potentially effective intervention for enhancing the knee osteoarthritis (KOA) patients' knee joint function (RR = 1.16, 95% CI: -2.58, 4.91), isometric knee flexion (RR = 2.49, 95% CI: -2.53, 7.50), knee extension (RR = -0.13, 95% CI: -0.45, 0.18), knee society score (KSS) (RR = 2.18, 95% CI: -1.51, 5.88), stair test (RR = -0.73, 95% CI: -1.84, 0.37), and timed up and go (RR = -1.18, 95% CI: -1.60, -0.76). CONCLUSIONS: Compared to interventions with less emphasis on balance training, rehabilitation programs highly emphasizing balance training significantly enhance the walking ability, balance specificity, and functional indicators of elderly patients post-TKA. This includes rehabilitation programs for senior TKA patients, with a focus on activities meant to improve the sensory system, balance in particular.

Polygenic Risk Score Reveals Genetic Heterogeneity of Alzheimer's Disease between the Chinese and European Populations.

BACKGROUND: The polygenic risk score (PRS) aggregates the effects of numerous genetic variants associated with a condition across the human genome and may help to predict late-onset Alzheimer's disease (LOAD). Most of the current PRS studies on Alzheimer's disease (AD) have been conducted in Caucasian ancestry populations, while it is less studied in Chinese. OBJECTIVE: To establish and examine the validity of Chinese PRS, and explore its racial heterogeneity. DESIGN: We constructed a PRS using both discovery (N = 2012) and independent validation samples (N = 1008) from Chinese population. The associations between PRS and age at onset of LOAD or cerebrospinal fluid (CSF) biomarkers were assessed. We also replicated the PRS in an independent replication cohort with CSF data and constructed an alternative PRS using European weights. SETTING: Multi-center genetics study. PARTICIPANTS: A total of 3020 subjects were included in the study. MEASUREMENTS: PRS was calculated using genome-wide association studies data and evaluated the performance alone (PRSnoAPOE) and with other predictors (full model: LOAD ~ PRSnoAPOE + APOE+ sex + age) by measuring the area under the receiver operating curve (AUC). RESULTS: PRS of the full model achieved the highest AUC of 84.0% (95% CI = 81.4-86.5) with pT< 0.5, compared with the model containing APOE alone (61.0%). The AUC of PRS with pT<5e-8 was 77.8% in the PRSnoAPOE model, 81.5% in the full model, and only ranged from 67.5% to 75.1% in the PRS with the European weights model. A higher PRS was significantly associated with an earlier age at onset (P <0.001). The PRS also performed well in the replication cohort of the full model (AUC=83.1%, 95% CI = 74.3-92.0). The CSF biomarkers of Aß42 and the ratio of Aß42/Aß40 were significantly inversely associated with the PRS, while p-Tau181 showed a positive association. CONCLUSIONS: This finding suggests that PRS reveal genetic heterogeneity and higher prediction accuracy of the PRS for AD can be achieved using a base dataset and validation within the same ethnicity. The effective PRS model has the clinical potential to predict individuals at risk of developing LOAD at a given age and with abnormal levels of CSF biomarkers in the Chinese population.

The Effects of Different Exercise Interventions on Patients with Subjective Cognitive Decline: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND OBJECTIVE: Exercise is a promising non-pharmacological therapy for subjective cognitive decline, but it is unclear which type of exercise is most effective. The objective was to assess the comparative effects and ranks of all exercise-based interventions on cognitive function in patients with subjective cognitive decline (SCD). METHOD: In this network meta-analysis, Online databases for Web of Science, PubMed, Embase, Medline, Cochrane Library and PsycINFO were searched from inception to April 30, 2023. The included studies are randomized controlled trials assessing the efficacy of exercise interventions for individuals with SCD. The primary outcome measure is memory, while secondary outcome measures encompass executive function, attention, verbal fluency, and global cognitive function. Represented using Standardized Mean Differences (SMDs) along with their 95% Confidence Intervals (CIs). Bias assessment was conducted in accordance with the 'Cochrane Risk of Bias Assessment Tool, 2nd Edition' (RoB 2). Pairwise meta-analysis was carried out using the 'meta-analysis' module within STATA 14.0, and network meta-analysis was performed using the 'mvmeta' and 'network' packages available in STATA 14.0. Registration number CRD42023289687. RESULT: This study included a total of 11 randomized controlled trials, encompassing 1,166 patients. Mind-body exercise was found to be efficacious in enhancing or sustaining memory (SMD: 0.58, 95%CI: 0.06 ~ 1.10) and executive function (SMD: 0.41, 95%CI: 0.09 ~ 0.73) in individuals with subjective cognitive decline. Furthermore, mind-body exercise exhibited the highest probability of being the most effective measures for improving or preventing the decline in memory (surface under cumulative ranking curve (SUCRA) value: 90.4) and executive function (SUCRA value: 91.8). The second-ranked moderate-intensity aerobic exercise has also shown a positive effect on the improvement of executive function in patients with subjective cognitive decline (SMD: 0.23, 95%CI: 0.03 ~ 0.43, SUCRA value: 68.2). However, we did not observe a significant effectiveness of exercise interventions on verbal fluency, attention, and overall cognitive function in subjective cognitive decline. CONCLUSION: Mind-body exercise may potentially be the optimal strategies for enhancing memory and executive function in individuals with subjective cognitive decline. Additionally, moderate-intensity aerobic exercise has shown a modest positive effect on executive function in subjective cognitive decline. When resources permit, practical application of these findings may be considered. Nevertheless, further support for the conclusions of this study is warranted through larger sample sizes and well-designed multicenter trials.

[The Miao medicine Sidaxue alleviates rheumatoid arthritis in rats possibly by downregulating matrix metalloproteinases].

OBJECTIVE: To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1ß levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. RESULTS: Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1ß, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. CONCLUSION: Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1ß/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.

[Adolescent female reproductive system dysplasia: a clinical study of 356 cases].

Objective: To explore the age of onset and consultation, the main clinical manifestations, common types of combined malformations, the relationship of endometriosis, surgical prognosis and different types of proportion of adolescent female reproductive system dysplasia. Methods: The medical records of 356 patients (aged 10-19) with female reproductive system dysplasia in Women's Hospital, School of Medicine, Zhejiang University from January 2003 to August 2018 were collected and retrospectively analyzed. Results: (1) Among the 356 adolescent dysplasia patients, uterine dysplasia (23.6%, 84/356), oblique vaginal septum syndrome (OVSS; 22.5%, 80/356) and vaginal dysplasia (21.6%, 77/356) were the most frequent ones, followed by multi-sectional dysplasia (16.0%, 57/356), other types of developmental abnormalities like external genitaliaand urogenital fistula (13.5%, 48/356) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome; 2.8%, 10/356). (2) There were significant differences between the median age of onset and the age of consultation of patients with OVSS and other types of abnormalities except hymen atresia (both P<0.05). In contrast, there were no significant differences between the age of onset and the age of consultation of the patients of uterine dysplasia, vaginal dysplasia, hymen atresia, MRKH syndrome and multi-sectional dysplasia (all P>0.05). (3) The clinical manifestations were lack of specificity, and mainly abnormal finding was lower abdominal pain. (4) After admission, the majority of patients underwent comprehensive cardiopulmonary examination (71.3%, 254/356) and urinary system examination (63.5%, 226/356). Only 18.3% (65/356) of patients had completed abdominal organ examination, and 5.9% (21/356) skeletal system examination. About other systemic malformations, urological malformations were the most common (27.5%, 98/356), followed by anorectal malformation (0.6%, 2/356), heart malformations (0.3%, 1/356), and spinal malformations (0.3%, 1/356). 46.4% (84/181) of the surgical patients were diagnosed with combined endometriosis. Patients with obstructive genital tract malformations were more likely to combine with endometriosis than non-obstructive ones [50.3% (74/147) vs 29.4% (10/34); P<0.05]. However, there was no significant difference between the severity of endometriosis of those two kinds (P>0.05). (5) Totally 308 patients were followed up successfully with a median of 25.0 years old, and 20 cases were treated again; 12.0% (37/308) of them were suffering from menstrual disorder and 33.1% (102/308) of them with dysmenorrhea. Totally 130 patients had sexually active reported no sexual problems. Conclusions: Uterine dysplasia, OVSS and vaginal dysplasia are the most common syndromes in adolescent female reproductive system dysplasia along with frequent cases of coexisting urinary malformations and increasing risks of endometriosis. Meanwhile, the lack of specificity of clinical manifestations might delay the timely diagnosis and treatment after the onset of symptoms. Nonetheless, most patients could achieve good surgical outcomes.

[Changes of hemodynamic parameters in normal pregnant women and their relationship with maternal basic characteristics].

Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

[Analysis of sequential chemotherapy efficacy in ovarian epithelial carcinoma, fallopian tube carcinoma and primary peritoneal carcinoma].

Objective: To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Methods: A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel's Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups. Results: (1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups (Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions: Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

[Association between sleep status in the first trimester and preterm birth].

Objective: To investigate the relationship between sleep status in the first trimester and preterm birth. Methods: Clinical data of pregnant women who received regular prenatal examination and delivered in Peking University Third Hospital from September 1, 2019 to June 10, 2020 were collected. The Pittsburgh sleep quality index (PSQI) was used to investigate their sleep status during 8-12 weeks of gestation, and the delivery outcomes were followed up. According to the gestational age at delivery and the cause of preterm birth, they were divided into full-term delivery group (204 cases), preterm birth group (13 cases) and spontaneous preterm birth group (9 cases). The correlation between the sleep status in the first trimester and preterm birth or spontaneous preterm birth was analyzed. Results: The median PSQI score of full-term delivery group was 4.0 points (3.0, 6.0 points), which was lower than those of preterm delivery group [6.0 points (4.0, 8.0 points)] and spontaneous preterm delivery group [7.0 points (4.0, 8.0 points)], and the differences were statistically significant (all P<0.05). The proportion of pregnant women with poor sleep quality (PSQI score>7 points) in full-term delivery group [14.2% (29/204)] was lower than those in preterm delivery group (5/13) and spontaneous preterm delivery group (4/9), and the differences were statistically significant (all P<0.05). Compared with the full-term delivery group [8.0 hours (7.0, 9.0 hours)], the preterm birth group [7.0 hours (7.0, 8.0 hours)] and spontaneous preterm birth group [7.0 hours (7.0, 8.0 hours)] had significantly shorter sleep duration at night (all P<0.05). Multivariate analysis showed that PSQI score in the first trimester was an independent risk factor for preterm birth (aOR=1.22, 95%CI: 1.02-1.45; P=0.026). Pregnancy with assisted reproductive technology (aOR=5.55, 95%CI: 1.22-25.31; P=0.027), gestational diabetes mellitus (aOR=9.27, 95%CI: 1.96-43.82; P=0.005), PSQI score in the first trimester (aOR=1.27, 95%CI: 1.01-1.58; P=0.039) were independent risk factors for spontaneous preterm birth. Conclusion: Attention should be paid to the decreased sleep quality in the first trimester, which might significantly increase the risk of preterm birth and spontaneous preterm birth.

Cardiac magnetic resonance imaging (MRI) for detecting acute myocardial injury of fulminant myocarditis survivors after extracorporeal membrane oxygenation (ECMO) treatment in adults.

AIMS: To detect the acute myocardial injury in fulminant myocarditis (FM) survivors after extracorporeal membrane oxygenation (ECMO) and to demonstrate its significant differences from non-FM patients by cardiac magnetic resonance (CMR). MATERIALS AND METHODS: This retrospective study enrolled 59 patients with acute myocarditis (AM), including 35 non-FM patients, 24 FM patients, and 54 controls. The peak value of cardiac troponin T (cTnT) was recorded. Tissue parameters, including native T1, extracellular volume (ECV), late gadolinium-enhancement (LGE)%, and T2 by CMR were assessed. RESULTS: The mean age was 35 ± 14 years, and 45.8% of the population were males in the AM group. Patients had higher levels of peak cTnT, peak NT-proBNP and peak C-reactive protein in the FM group (all p<0.05). Comparing with non-FM, the values of T1-based imaging parameters were significantly higher in the FM group (all p<0.05). In contrast, no difference was observed among the two groups in terms of T2 value (p=0.707). The septal area was more frequently involved in FM survivors after ECMO treatment, both in T1 and T2-based images. In addition, the cubic relationship was the relative best fit of LGE% against logcTnT and indicated that cTnT value exceeding 300ng/L exhibited a rapid upward trend of LGE%. CONCLUSION: Comparing to non-FM, higher myocardial necrosis and fibrosis but similar edema determined by T1 and T2 based imaging was found in FM survivors after ECMO treatment. Furthermore, the inter-ventricular septal area was more frequently involved by acute myocardial injury in FM survivors after ECMO treatment. In addition, LGE% showed an overall increasing trend with cTnT values elevating with rapidly increasing with cTnT exceeding 300 ng/L.

[Dynamic monitoring and esthetic evaluation of dimensional changes in the peri-implant soft tissue contour after the immediate implant placement and provisionalization with the modified socket-shield technique in the esthetic zone].

Objective: To accurately measure the dynamic changes of peri-implant soft tissue within one year after the immediate implant placement and provisionalization with the modified socket-shield technique (MSST) in the esthetic zone, and to provide a basis for evaluating the effect of the modified socket-shield technique on the maintenance of peri-implant soft tissue. Methods: A total of 22 patients (22 implants) were prospectively included 1 year after completion of immediate implant placement and provisionalization (IIPP) within MSST in the esthetic zone from January 2022 to January 2024 at the Department of Oral Implantology in the Stomatological Hospital of Chongqing Medical University. The patients were (40±13) years old (21-75 years), including 9 males and 13 females. The intraoral optical models of patients were obtained by an intraoral scanner system preoperatively and at 3, 6, and 12 months postoperatively, respectively. The standard tessellation language files of intraoral optical models at multiple time points were imported to Geomagic Studio 2013 to be superimposed and aligned for analyzing the peri-implant soft tissue contour on the labial side of the implant site at multiple levels. The amount of gingival margin recession, gingival papilla change, and thickness change of the labial side of the soft tissues at each postoperative point in time were measured at each postoperative time point, as well as evaluating the esthetic effect by the pink esthetic score (PES). Results: No adverse events occurred in all the implants during the 12-month follow-up period. The recession level of the gingival margin of the implant site (GL) was 0.08 (0.07) mm, the recession level of the mesial papilla (ML) was 0.19 (0.25) mm, and the recession level of the distal papilla (DL) was 0.19 (0.10) mm. The average collapse thickness of the soft tissue contour on the labial side of the implant (ΔD) was (0.39±0.09) mm, mainly occurring within 2 mm of the root of the gingival margin. The height of the alveolar bone was reduced by (0.17±0.08) mm. The thickness of the labial alveolar bone at 1, 3, and 5 mm root side of the implant shoulder was reduced by (0.13±0.08), (0.12±0.10) and 0.04 (0.17) mm, respectively. The postoperative pink esthetic score was 13.00 (2.25) points at 12 months, which suggested that all implant sites achieved ideal esthetic results. Conclusions: The labial soft tissue contour at implant sites shows minimal change following immediate implant placement and provisionalization using the modified socket-shield technique for 1 year in the esthetic zone.

[Patient-derived parotid gland pleomorphic adenoma organoid model and its preliminary histological and functional characterization].

Objective: To establish patient-derived organoid models of pleomorphic adenomas (PAs) of the parotid gland and preliminarily characterize their histology, related biomarkers and functions. Methods: Fresh tumor tissue specimens were collected from surgical procedures of Oral and Maxillofacial Department. The harvested tissues were processed and cultured in a head and neck tumor organoid culture system, resulting in the successful establishment of organoid models from four cases of parotid gland pleomorphic adenomas. The in vitro growth of PA organoids was recorded by light microscopy. The successfully established organoids were passaged and cryopreserved, and the cryopreserved PA organoids were revived and re-cultured to observe their viability and organoid regeneration ability. Histological characterization, as well as characterization and detection of related markers and functional proteins, were performed on the organoids, comparing them with the patient-derived tissues. Results: The constructed organoid model of pleomorphic adenoma exhibited a dense and compact three-dimensional spherical structure. Hematoxylin and eosin staining indicated morphological similarities between the organoid and its tissue of origin. Immunohistochemistry showed positive cytoplasmic staining for Calponin, CK7, and EMA in both the organoid and the source tumor tissue, suggesting consistent histopathological characteristics between the organoid and its tissue of origin. Periodic acid-Schiff staining of the organoid showed positive staining for glycogen, with positive staining located in the interior and periphery of the organoid, indicating that the organoid possessed secretory functions like the salivary gland. Conclusion: We successfully constructed organoids of pleomorphic adenoma derived from patient samples. This model faithfully replicates the tissue morphology and biomarkers of the source tissue and exhibits biological functions associated with mucus secretion. It serves as a valuable in vitro model for studying the development and progression of salivary gland tumors.

Deep Learning-Based Facial and Skeletal Transformations for Surgical Planning.

The increasing application of virtual surgical planning (VSP) in orthognathic surgery implies a critical need for accurate prediction of facial and skeletal shapes. The craniofacial relationship in patients with dentofacial deformities is still not understood, and transformations between facial and skeletal shapes remain a challenging task due to intricate anatomical structures and nonlinear relationships between the facial soft tissue and bones. In this study, a novel bidirectional 3-dimensional (3D) deep learning framework, named P2P-ConvGC, was developed and validated based on a large-scale data set for accurate subject-specific transformations between facial and skeletal shapes. Specifically, the 2-stage point-sampling strategy was used to generate multiple nonoverlapping point subsets to represent high-resolution facial and skeletal shapes. Facial and skeletal point subsets were separately input into the prediction system to predict the corresponding skeletal and facial point subsets via the skeletal prediction subnetwork and facial prediction subnetwork. For quantitative evaluation, the accuracy was calculated with shape errors and landmark errors between the predicted skeleton or face with corresponding ground truths. The shape error was calculated by comparing the predicted point sets with the ground truths, with P2P-ConvGC outperforming existing state-of-the-art algorithms including P2P-Net, P2P-ASNL, and P2P-Conv. The total landmark errors (Euclidean distances of craniomaxillofacial landmarks) of P2P-ConvGC in the upper skull, mandible, and facial soft tissues were 1.964 ± 0.904 mm, 2.398 ± 1.174 mm, and 2.226 ± 0.774 mm, respectively. Furthermore, the clinical feasibility of the bidirectional model was validated using a clinical cohort. The result demonstrated its prediction ability with average surface deviation errors of 0.895 ± 0.175 mm for facial prediction and 0.906 ± 0.082 mm for skeletal prediction. To conclude, our proposed model achieved good performance on the subject-specific prediction of facial and skeletal shapes and showed clinical application potential in postoperative facial prediction and VSP for orthognathic surgery.

[Clinical features and follow-up study on 55 patients with adolescence-onset methylmalonic acidemia].

Objective: To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies. Methods: This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months. Results: Among the 55 patients, 31 were males and 24 were females. The median age of onset was 12 years old (range 10-18 yearsold). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work. Conclusions: Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

[Feasibility analysis of the application of programmed process endoscopic lateral neck dissection via chest-breast approach in papillary thyroid carcinoma surgery].

Objective: To explore the feasibility of endoscopic lymph node dissection(LND) with programmed breast approach for the treatment of papillary thyroid cancer. Methods: A case series study. The clinical data of 39 patients with papillary thyroid cancer who underwent endoscopic LND treatment with programmed breast approach in Shenzhen People's Hospital from January to November 2022 were retrospectively analyzed. There were 10 males and 29 females, aged (35.95±10.17) years. LND time, total surgical time, intraoperative bleeding volume, postoperative drainage volume, postoperative hospital stay and postoperative complications were analyzed. Results: Among 39 patients, there were 18 cases of unilateral thyroid cancer, 21 cases of bilateral thyroid cancer, 35 cases of unilateral LND, and 4 cases of bilateral LND. The maximum diameter of thyroid cancer lesions was (1.48±0.69) cm, and the maximum diameter of lymph node metastases was (1.63±0.58)cm. The operative time of unilateral neck dissection was (124.11±19.92) min (102-170 min), and the total operative time was (226.42±55.68) min (110-390 min). The number of lymph nodes cleaned was (32.40±10.44)(12-54), the number of metastasis and detection was 207/1 393. The postoperative drainage volume was (174.64±82.33) ml(41-350 ml). There were no neck hematomas, no skin burns or no shrugging disorders in the postoperative period. There were 7 cases of numbness and discomfort in neck skin sensation, which gradually relieved after half a year. Postoperative discharge time (4.77±1.94) d(3-15 d). Conclusion: It is safe and feasible to treat papillary thyroid cancer with endoscopic LND with programmed breast approach, which can improve surgical efficiency and clinical application value.

The complexity of glucose time series is associated with short- and long-term mortality in critically ill adults: a multi-center, prospective, observational study.

BACKGROUND: The wealth of data taken from continuous glucose monitoring (CGM) remains to be fully used. We aimed to evaluate the relationship between a promising new CGM metric, complexity of glucose time series index (CGI), and mortality in critically ill patients. METHODS: A total of 293 patients admitted to mixed medical/surgical intensive care units from 5 medical centers in Shanghai were prospectively included between May 2020 and November 2021. CGI was assessed using intermittently scanned CGM, with a median monitoring period of 12.0 days. Outcome measures included short- and long-term mortality. RESULTS: During a median follow-up period of 1.7 years, a total of 139 (47.4%) deaths were identified, of which 73 (24.9%) occurred within the first 30 days after ICU admission, and 103 (35.2%) within 90 days. The multivariable-adjusted HRs for 30-day mortality across ascending tertiles of CGI were 1.00 (reference), 0.68 (95% CI 0.38-1.22) and 0.36 (95% CI 0.19-0.70), respectively. For per 1-SD increase in CGI, the risk of 30-day mortality was decreased by 51% (HR 0.49, 95% CI 0.35-0.69). Further adjustment for HbA1c, mean glucose during hospitalization and glucose variability partially attenuated these associations, although the link between CGI and 30-day mortality remained significant (per 1-SD increase: HR 0.57, 95% CI 0.40-0.83). Similar results were observed when 90-day mortality was considered as the outcome. Furthermore, CGI was also significantly and independently associated with long-term mortality (per 1-SD increase: HR 0.77, 95% CI 0.61-0.97). CONCLUSIONS: In critically ill patients, CGI is significantly associated with short- and long-term mortality.

Campothecin suppresses cell proliferation and migration in head and neck squamous cell carcinoma by blocking RAB27A-mediated phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway.

Camptothecin (CPT), a naturally occurring alkaloid derived from the Camptotheca acuminate plant, exerts anti-tumor properties. However, its specific impact on head and neck squamous cell carcinoma (HNSCC) remains uncertain. The study was to explore the action and mechanism of CPT on HNSCC cells. First, two HNSCC cell lines (FaDu and TU686) and a normal immortalized keratinocyte (HEK001) cell line, were exposed to a spectrum of CPT concentrations (ranging from 10 to 50 µM) for durations of 24 h and 48 h. Cell viability, proliferation, migration, and invasion were assessed by CCK-8 assay, EdU incorporation assay, wound healing assay and transwell assay. Subsequently, si-RAB27A or negative control (NC) was introduced into FaDu and TU686 cells through transfection, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was manipulated with L740Y-P, an activator of this pathway. The expression of proliferating cell nuclear antigen (PCNA), E-cadherin, PI3K/AKT signaling factors and RAB27A were determined by Western blot analysis. RAB27A was detected by immunofluorescence assay. It was found that CPT significantly hindered the viability, proliferation (p<0.01), migration (p<0.001), and invasion (p<0.001) of FaDu and TU686 cells. At the molecular level, administration of CPT caused a decline in the expression of PCNA, P-PI3K, P-AKT, and RAB27A, alongside an elevation in E-cadherin levels within HNSCC cells (p<0.05, p<0.01 and p<0.001). Reducing RAB27A expression enhanced the suppressive impacts of CPT on HNSCC cell viability (p<0.05 and p<0.01), migration (p<0.001) and invasion (p<0.01), these effects that were reversed upon treatment with L740Y-P in HNSCC cells (p<0.001). In summary, our study highlights the efficacy of CPT in HNSCC, demonstrating its influence on cell processes via the RAB27A-mediated PI3K/AKT pathway.

Modulation of the microRNA-6089/E2F transcription factor2 axis by querceting: implications for osteoblast viability, proliferation, migration, and osteogenic differentiation in fracture healing.

Quercetin is widely distributed in plants as a flavonol compound with multiple biological activities. It has been found that quercetin can regulate bone homeostasis through multiple pathways and targets. This study investigated the role and specific molecular mechanisms of quercetin in regulating osteoblast viability, proliferation, migration and osteogenic differentiation. A mouse model of traumatic fracture was established and then 100 mg/kg quercetin corn oil suspension was gavaged at the same time every day for 28 days. miR-6089 and E2F transcription factor 2 (E2F2) expression levels in mice were measured. Fracture healing in mice was observed. MC3T3-E1 cells were transfected with plasmids targeting miR-6089 and E2F2, and cell viability, proliferation, migration, apoptosis, and osteogenic differentiation were determined. The targeting relationship between miR-6089 and E2F2 was verified. In vivo experiments showed that quercetin significantly increased osteocalcin (OCN) expression (P<0.05) and promoted fracture healing in traumatic fracture (TF) mice. miR-6089 expression was down-regulated (P<0.05) and E2F2 expression was up-regulated (P<0.05) in TF mice. Quercetin promoted miR-6089 expression and inhibited E2F2 expression (both P<0.05). In vitro results showed that quercetin promoted miR-6089 expression and inhibited E2F2 expression in a dose-dependent manner (both P<0.05). Quercetin dose-dependently promoted MC3T3-E1 cell viability, proliferation, migration, and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). Up-regulating miR-6089 further promoted MC3T3-E1 cell viability, proliferation, migration and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). miR-6089 targeted and regulated E2F2 expression. Up-regulating E2F2 attenuated the promoting effect of up-regulated miR-6089 on MC3T3-E1 cell viability, proliferation, migration, osteogenic differentiation, and inhibition of apoptosis (all P<0.05). We conclude that quercetin enhances osteoblast viability, proliferation, migration, and osteogenic differentiation by modulating the miR-6089/E2F2 axis, thereby promoting fracture healing.