This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans ; Ribosomes/physiology* ; Ribosomal Proteins/metabolism* ; Mutation ; Animals ; Cell Nucleolus/metabolism* ; Protein Biosynthesis ; Phase Separation

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

OBJECTIVE: To observe the characteristics of changes in non-invasive hemodynamic parameters in neonates with septic shock so as to provide clinical reference for diagnosis and treatment. METHODS: A observational study was conducted. The neonates with sepsis complicated with septic shock or not admitted to neonatal intensive care unit (NICU) of the First Affiliated Hospital of Shantou University Medical College were enrolled as the study subjects, who were divided into preterm infant (< 37 weeks) and full-term infant (≥ 37 weeks) according to the gestational age. Healthy full-term infants and hemodynamically stable preterm infants transferring to NICU after birth were enrolled as controls. Electronic cardiometry (EC) was used to measure hemodynamic parameters, including heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), stroke volume index (SVI), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI), before treatment in the septic shock group, at the time of diagnosis of sepsis in the sepsis without shock group, and before the discharge from the obstetric department or on the day of transferring to NICU in the control group. RESULTS: Finally, 113 neonates with complete data and parental consent for non-invasive hemodynamic monitoring were enrolled, including 32 cases in the septic shock group, 25 cases in the sepsis without shock group and 56 cases in the control group. In the septic shock group, there were 17 cases at the compensated stage and 15 cases at the decompensated stage. There were 21 full-term infants (20 cured or improved and 1 died) and 11 premature infants (7 cured or improved and 4 died), with the mortality of 15.62% (5/32). There were 18 full-term infants and 7 premature infants in the sepsis without shock group and all cured or improved without death. The control group included 28 full-term infants and 28 premature infants transferring to NICU after birth. Non-invasive hemodynamic parameter analysis showed that SV, SVI, CO and CI of full-term infants in the septic shock group were significantly lower than those in the sepsis without shock group and control group [SV (mL): 3.52±0.99 vs. 5.79±1.32, 5.22±1.02, SVI (mL/m²): 16.80 (15.05, 19.65) vs. 27.00 (22.00, 32.00), 27.00 (23.00, 29.75), CO (L/min): 0.52±0.17 vs. 0.80±0.14, 0.72±0.12, CI (mL×s^-1×m^-2): 40.00 (36.67, 49.18) vs. 62.51 (56.34, 70.85), 60.01 (53.34, 69.68), all P < 0.05], while SVR and SVRI were significantly higher than those in the sepsis without shock group and control group [SVR (kPa×s×L^-1): 773.46±291.96 vs. 524.17±84.76, 549.38±72.36, SVRI (kPa×s×L^-1×m^-2): 149.27±51.76 vs. 108.12±12.66, 107.81±11.87, all P < 0.05]. MAP, SV, SVI, CO and CI of preterm infants in the septic shock group were significantly lower than those in the control group [MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 38.55±10.48 vs. 47.46±2.85, SV (mL): 2.45 (1.36, 3.58) vs. 3.96 (3.56, 4.49), SVI (mL/m²): 17.60 (14.20, 25.00) vs. 25.50 (24.00, 29.00), CO (L/min): 0.32 (0.24, 0.63) vs. 0.56 (0.49, 0.63), CI (mL×s^-1×m^-2): 40.01 (33.34, 53.34) vs. 61.68 (56.68, 63.35), all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 1 082.88±689.39 vs. 656.63±118.83, SVRI (kPa×s×L^-1×m^-2): 126.00±61.50 vs. 102.37±11.68, both P > 0.05]. Further analysis showed that SV, SVI and CI of neonates at the compensation stage in the septic shock group were significantly lower than those in the control group [SV (mL): 3.60±1.29 vs. 4.73±1.15, SVI (mL/m²): 19.20±8.33 vs. 26.34±3.91, CI (mL×s^-1×m^-2): 46.51±20.34 vs. 61.01±7.67, all P < 0.05], while MAP, SVR and SVRI were significantly higher than those in the control group [MAP (mmHg): 52.06±8.61 vs. 48.54±3.21, SVR (kPa×s×L^-1): 874.95±318.70 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 165.07±54.90 vs. 105.09±11.99, all P < 0.05]; MAP, SV, SVI, CO and CI of neonates at the decompensated stage in the septic shock group were significantly lower than those in the control group [MAP (mmHg): 35.13±6.08 vs. 48.54±3.21, SV (mL): 2.89±1.17 vs. 4.73±1.15, SVI (mL/m²): 18.50±4.99 vs. 26.34±3.91, CO (L/min): 0.41±0.19 vs. 0.65±0.15, CI (mL×s^-1×m^-2): 43.34±14.17 vs. 61.01±7.67, all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 885.49±628.04 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 114.29±43.54 vs. 105.09±11.99, both P > 0.05]. CONCLUSIONS Full-term infant with septic shock exhibit a low cardiac output, high vascular resistance hemodynamic pattern, while preterm infant with septic shock show low cardiac output and normal vascular resistance. At the compensated stage the hemodynamic change is low output and high resistance type, while at the decompensated stage it is low output and normal resistance type. Non-invasive hemodynamic monitoring can assist in the identification of neonatal septic shock and provide basis for clinical diagnosis and treatment.
Humans ; Shock, Septic/physiopathology* ; Infant, Newborn ; Hemodynamics ; Female ; Male ; Case-Control Studies ; Infant, Premature

Objective : To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC). Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay. Results : The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines. Conclusion The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.

Objective:To examine the therapeutic strategy and its impacting factors by analyzing the perioperative outcomes of total thoracoscopic repeat mitral valve surgery under moderate hypothermia-induced ventricular fibrillation with cardiopulmonary bypass.Methods:This study is a retrospective case series. Totally 63 patients who underwent repeat mitral valve surgery by the same surgeon from January 2021 to December 2023 in Department of Cardiovascular Surgery, the First Medical Center of People′s Liberation Army General Hospital were retrospectively enrolled. There were 28 males and 35 females with an age of (58.3±15.9) years (range: 13 to 84 years). Surgery was performed using a totally thoracoscopic approach under moderate hypothermia-induced ventricular fibrillation. Mitral valvuloplasty was completed in 32 cases and mitral valve replacement in 31 cases. Preoperative baseline data and perioperative outcomes of the patients were collected and Logistic regression was used to analyze independent influencing factors of premature ventricular contractions in the early postoperative period.Results:The intraoperative cardiopulmonary bypass time was (191.5±50.9) minutes (range: 95 to 286 minutes), and the hypothermic ventricular fibrillation time was (99.0±39.8) minutes (range: 34 to 203 minutes). The anal temperature before the start of cardiopulmonary bypass was (36.3±0.5) ℃ (range: 35.2 to 38.0 ℃), the lowest intraoperative anal temperature was (27.3±1.3) ℃(range: 23.7 to 30.1 ℃), and the anal temperature at the time of the cessation of cardiopulmonary bypass was (36.3±0.4) ℃ (range: 35.2 to 37.0 ℃), and excessive rewarming was observed in 33 cases. Six cases applied the artificial heart assist device. Seventeen cases developed premature ventricular contractions in the early postoperative period. Two cases developed neurologic complications. Five cases developed respiratory complications. One case developed urological systemic complications. Six cases were mechanically ventilated for more than 3 days, and the duration of ICU stay in 16 cases was more than 3 days and the postoperative discharge time of ( M(IQR)) 8.0 (3.5) days (range: 3 to 26 days). Two cases died or were discharged voluntarily. Logistic regression results showed that persistent preoperative atrial fibrillation ( OR=11.424, 95% CI: 1.477 to 144.564, P=0.033) and excessive rewarming ( OR=15.249, 95% CI: 1.357 to 279.571, P=0.038) were independent risk factors for the appearance of premature ventricular contractions in the early postoperative period. Conclusions:The technique of total thoracoscopic surgery under induced moderate hypothermic ventricular fibrillation with cardiopulmonary bypass could be applied to repeated mitral valve surgeries with less trauma and faster recovery. Persistent preoperative atrial fibrillation and excessive rewarming are independent risk factors for the occurrence of premature ventricular contractions in the early postoperative period.

Objective:To examine the therapeutic strategy and its impacting factors by analyzing the perioperative outcomes of total thoracoscopic repeat mitral valve surgery under moderate hypothermia-induced ventricular fibrillation with cardiopulmonary bypass.Methods:This study is a retrospective case series. Totally 63 patients who underwent repeat mitral valve surgery by the same surgeon from January 2021 to December 2023 in Department of Cardiovascular Surgery, the First Medical Center of People′s Liberation Army General Hospital were retrospectively enrolled. There were 28 males and 35 females with an age of (58.3±15.9) years (range: 13 to 84 years). Surgery was performed using a totally thoracoscopic approach under moderate hypothermia-induced ventricular fibrillation. Mitral valvuloplasty was completed in 32 cases and mitral valve replacement in 31 cases. Preoperative baseline data and perioperative outcomes of the patients were collected and Logistic regression was used to analyze independent influencing factors of premature ventricular contractions in the early postoperative period.Results:The intraoperative cardiopulmonary bypass time was (191.5±50.9) minutes (range: 95 to 286 minutes), and the hypothermic ventricular fibrillation time was (99.0±39.8) minutes (range: 34 to 203 minutes). The anal temperature before the start of cardiopulmonary bypass was (36.3±0.5) ℃ (range: 35.2 to 38.0 ℃), the lowest intraoperative anal temperature was (27.3±1.3) ℃(range: 23.7 to 30.1 ℃), and the anal temperature at the time of the cessation of cardiopulmonary bypass was (36.3±0.4) ℃ (range: 35.2 to 37.0 ℃), and excessive rewarming was observed in 33 cases. Six cases applied the artificial heart assist device. Seventeen cases developed premature ventricular contractions in the early postoperative period. Two cases developed neurologic complications. Five cases developed respiratory complications. One case developed urological systemic complications. Six cases were mechanically ventilated for more than 3 days, and the duration of ICU stay in 16 cases was more than 3 days and the postoperative discharge time of ( M(IQR)) 8.0 (3.5) days (range: 3 to 26 days). Two cases died or were discharged voluntarily. Logistic regression results showed that persistent preoperative atrial fibrillation ( OR=11.424, 95% CI: 1.477 to 144.564, P=0.033) and excessive rewarming ( OR=15.249, 95% CI: 1.357 to 279.571, P=0.038) were independent risk factors for the appearance of premature ventricular contractions in the early postoperative period. Conclusions:The technique of total thoracoscopic surgery under induced moderate hypothermic ventricular fibrillation with cardiopulmonary bypass could be applied to repeated mitral valve surgeries with less trauma and faster recovery. Persistent preoperative atrial fibrillation and excessive rewarming are independent risk factors for the occurrence of premature ventricular contractions in the early postoperative period.

Objective:To compare the clinical efficacy of ileocecal-preserving laparoscopic subtotal colectomy, antegrade peristaltic ascending colorectal anastomosis with antiperistalsis cecorectal anastomosis in the treatment of severe slow transit constipation.Methods:The clinical data of 42 patients with severe slow transit constipation undergoing surgery in Shulan (Hangzhou) Hospital from Jan 2016 to Oct 2021 were retrospectively analyzed. All 42 patients underwent ileocecal-preserving laparoscopic subtotal colectomy. Among them, 25 patients underwent antegrade peristaltic anastomosis of ascending colon and rectum, 17 patients underwent antiperistaltic anastomosis of cecum and rectum.Results:There was no significant difference in the operation time and hospitalization time between the two groups ( t=-0.464, P=0.645; t=0.010, P=0.992); Wexner constipation scores in both groups were significantly reduced at 6 and 12 months after surgery. There was no significant difference in the Wexner constipation scores ( t=-1.181, P=0.240; t=-1.717, P=0.090), the number of bowel movenents per day ( t=0.179, P=0.860; t=0.545, P=0.590) and stool shapes scores ( t=-0.316, P=0.750; t=0.447, P=0.660) between the two groups at 6 and 12 months after surgery. Gastrointestinal quality of life index scores in the antegrade peristaltic anastomosis group were significantly higher than those in the antiperistalsis anastomosis group at 6 and 12 months after surgery ( t=4.329, P<0.05; t=3.988, P<0.05), while abdominal pain scores were significantly lower than those in the antiperistalsis anastomosis group ( t=-4.386, P<0.05; t=-5.740, P<0.05). Conclusions:For patients with severe slow transit constipation, ileocecal-preserving laparoscopic subtotal colectomy has good surgical safety and near-to-medium-term clinical efficacy, whether it is antegrade peristaltic ascending colorectal anastomosis (the stump of the ascending colon is turned from front to back) or antiperistalsis cecorectal anastomosis. The antegrade peristaltic ascending colorectal anastomosis has lower abdominal pain score and better gastrointestinal quality of life than antiperistalsis cecorectal anastomosis, which should be recommended first. During the operation, the ileocolic mesentery should be fully separated to the root of mesentery and the ileocecal part should be turned from front to back to avoid the occurrence of mesenteric vascular torsion and small intestinal obstruction.