OBJECTIVE: To assess the feasibility of first polar body transfer (PB1T) combined with preimplantation mitochondrial genetic testing for blocking the transmission of a pathogenic mitochondrial DNA 8993T>G mutation. METHODS: A Chinese family affected with Leigh syndrome which had attended the Reproductive Medicine Centre of the First Affiliated Hospital of Anhui Medical University in September 2021 was selected as the study subject. Controlled ovarian hyperstimulation was carried out for the proband after completing the detection of the mitochondrial DNA 8993T>G mutation load among the pedigree members. Mature MII oocytes were inseminated by intracytoplasmic sperm injection (ICSI), cultured in vitro for 5 to 6 days to the blastocyst stage, and trophoblastocytes were obtained by microbiopsy. Mitochondrial DNA testing (PGT-MT) and chromosomal aneuploidy (PGT-A) analyses were carried out after whole-genome amplification, and the embryos with zero mutation load were selected for transfer. Amniotic fluid and umbilical cord blood samples were collected during middle pregnancy and after birth respectively for mitochondrial DNA testing to verify the reliability of embryo screening. As an attempt, PB1 with good morphology of MII oocytes was selected for transfer into the enucleated oocytoplasm from healthy donors, followed by ICSI fertilization, blastocyst culture and PGT of embryos using the same procedure. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (No. 2021zhyx-B12). RESULTS: An antagonist protocol was used for ovarian stimulation, and a total of 19 oocytes were obtained, of which 14 MII were fertilized by ICSI, and 2 had developed into blastocysts. PGT-MT was carried out on biopsied trophoblastocytes, in which the mitochondrial DNA 8993T>G mutation load was not detected in one embryo, the other was 100% mutated, and the mutation loads of the remaining unfertilized eggs and developmentally arrested embryos ranged from 0% ~ 100%, presenting a clear biased distribution. With fully informed consent, one PGT-MT zero mutation load blastocyst was transferred and clinical pregnancy was achieved. Mitochondrial DNA and chromosomal testing of amniotic fluid cells during middle pregnancy had revealed no abnormalities. The proband had delivered a healthy boy through Caesarean section at 39⁺⁵ weeks of gestation, and no mutation was detected in the cord blood sample. Five well-formed PBs from 14 eggs were selected for PB1 transfer, followed by ICSI and culture, and two of the reconstituted embryos had formed blastocysts, with none of the above mutations detected in the biopsied samples. CONCLUSION The PGT-MT technology can help families affected with mitochondrial diseases to have healthy offspring. PB1 transfer in combination with ICSI and PGT-MT holds the promise of turning waste into treasure and providing an alternative means of fertility for such families.
Humans ; Preimplantation Diagnosis/methods* ; Female ; DNA, Mitochondrial/genetics* ; Genetic Testing/methods* ; Pregnancy ; Mitochondrial Diseases/genetics* ; Polar Bodies ; Adult ; Feasibility Studies ; Sperm Injections, Intracytoplasmic/methods* ; Embryo Transfer/methods* ; Mutation ; Male ; Blastocyst/metabolism* ; Pedigree

Objective:To evaluate the effect of the degree of neuromuscular blockade on the intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion.Methods:In this randomized controlled trial, 100 patients of either sex, aged 18-79 yr, with a body mass index of 18.5-35.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification < Ⅳ, scheduled for elective lumbar interbody fusion at the Affiliated Hospital of Xuzhou Medical University from August to October 2024, were allocated into 2 groups ( n=50 each) using stratified randomization based on the number of lumbar segments: deep neuromuscular blockade group (group D) and moderate neuromuscular blockade group (group M). The intraoperative post-tetanic count was maintained at 1 or 2 in group D, and the intraoperative train-of-four was maintained at 1 or 2 in group M. The scores for surgical conditions, duration of operation, blood loss, length of incision, occurrence of severe hypoxemia after extubation, requirement for rescue analgesia in post-anesthesia care unit, 15-item Quality of Recovery scale score and length of stay were recorded. Results:Compared with group M, the scores for surgical conditions were significantly increased, the rate of rescue analgesia in post-anesthesia care unit was decreased, 15-item Quality of Recovery scale scores were increased at 3 days after surgery ( P<0.05), and no significant changes were found in the duration of operation, blood loss, length of incision, incidence of severe hypoxemia after extubation and length of hospital stay in group D ( P>0.05). Conclusions:Compared with moderate neuromuscular blockade, deep neuromuscular blockade can provide better surgical conditions and improve the quality of early postoperative recovery for patients undergoing lumbar interbody fusion.

Congenital hyperinsulinism is the most common cause of hypoglycemia in children, characterized by a complex genetic basis, diverse pathogenic mechanisms, and significant clinical heterogeneity.Delayed diagnosis and treatment can lead to irreversible neurological sequelae, including epilepsy and psychomotor retardation.In this review, recent advancements in the molecular genetics, imaging localization, therapeutic strategies, and follow-up outcomes of congenital hyperinsulinism were summarized so as to offer valuable insights for its clinical management.

Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.

Objective:To evaluate the effect of the degree of neuromuscular blockade on the intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion.Methods:In this randomized controlled trial, 100 patients of either sex, aged 18-79 yr, with a body mass index of 18.5-35.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification < Ⅳ, scheduled for elective lumbar interbody fusion at the Affiliated Hospital of Xuzhou Medical University from August to October 2024, were allocated into 2 groups ( n=50 each) using stratified randomization based on the number of lumbar segments: deep neuromuscular blockade group (group D) and moderate neuromuscular blockade group (group M). The intraoperative post-tetanic count was maintained at 1 or 2 in group D, and the intraoperative train-of-four was maintained at 1 or 2 in group M. The scores for surgical conditions, duration of operation, blood loss, length of incision, occurrence of severe hypoxemia after extubation, requirement for rescue analgesia in post-anesthesia care unit, 15-item Quality of Recovery scale score and length of stay were recorded. Results:Compared with group M, the scores for surgical conditions were significantly increased, the rate of rescue analgesia in post-anesthesia care unit was decreased, 15-item Quality of Recovery scale scores were increased at 3 days after surgery ( P<0.05), and no significant changes were found in the duration of operation, blood loss, length of incision, incidence of severe hypoxemia after extubation and length of hospital stay in group D ( P>0.05). Conclusions:Compared with moderate neuromuscular blockade, deep neuromuscular blockade can provide better surgical conditions and improve the quality of early postoperative recovery for patients undergoing lumbar interbody fusion.

Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To assess the feasibility of first polar body transfer (PB1T) combined with preimplantation mitochondrial genetic testing for blocking the transmission of a pathogenic mitochondrial DNA 8993T>G mutation.Methods:A Chinese family affected with Leigh syndrome which had attended the Reproductive Medicine Centre of the First Affiliated Hospital of Anhui Medical University in September 2021 was selected as the study subject. Controlled ovarian hyperstimulation was carried out for the proband after completing the detection of the mitochondrial DNA 8993T>G mutation load among the pedigree members. Mature MII oocytes were inseminated by intracytoplasmic sperm injection (ICSI), cultured in vitro for 5 to 6 days to the blastocyst stage, and trophoblastocytes were obtained by microbiopsy. Mitochondrial DNA testing (PGT-MT) and chromosomal aneuploidy (PGT-A) analyses were carried out after whole-genome amplification, and the embryos with zero mutation load were selected for transfer. Amniotic fluid and umbilical cord blood samples were collected during middle pregnancy and after birth respectively for mitochondrial DNA testing to verify the reliability of embryo screening. As an attempt, PB1 with good morphology of MⅡ oocytes was selected for transfer into the enucleated oocytoplasm from healthy donors, followed by ICSI fertilization, blastocyst culture and PGT of embryos using the same procedure. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (No. 2021zhyx-B12). Results:An antagonist protocol was used for ovarian stimulation, and a total of 19 oocytes were obtained, of which 14 MⅡ were fertilized by ICSI, and 2 had developed into blastocysts. PGT-MT was carried out on biopsied trophoblastocytes, in which the mitochondrial DNA 8993T>G mutation load was not detected in one embryo, the other was 100% mutated, and the mutation loads of the remaining unfertilized eggs and developmentally arrested embryos ranged from 0% ~ 100%, presenting a clear biased distribution. With fully informed consent, one PGT-MT zero mutation load blastocyst was transferred and clinical pregnancy was achieved. Mitochondrial DNA and chromosomal testing of amniotic fluid cells during middle pregnancy had revealed no abnormalities. The proband had delivered a healthy boy through Caesarean section at 39+ 5 weeks of gestation, and no mutation was detected in the cord blood sample. Five well-formed PBs from 14 eggs were selected for PB1 transfer, followed by ICSI and culture, and two of the reconstituted embryos had formed blastocysts, with none of the above mutations detected in the biopsied samples.Conclusion:The PGT-MT technology can help families affected with mitochondrial diseases to have healthy offspring. PB1 transfer in combination with ICSI and PGT-MT holds the promise of turning waste into treasure and providing an alternative means of fertility for such families.

OBJECTIVE: To investigate the feasibility and prognostic implications of assessing volume status during early fluid resuscitation in septic patients based on estimated plasma volume status (ePVS). METHODS: A prospective study was conducted. Patients with sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of Kunming Medical University from March to December in 2023 were enrolled. The general information and laboratory indicators at ICU admission were recorded, and ePVS, sequential organ failure assessment (SOFA) score, acute physiology and chronic health status evaluation II (APACHE II) score were calculated. The vital signs, arterial blood gas analysis and volume status related indicators before liquid resuscitation (T0h) and 3 hours (T3h) and 6 hours (T6h) of fluid resuscitation were recorded. The diameter and variability of the inferior vena cava (IVC) were measured by ultrasound, and ePVS, percentage change value of estimated plasma volume status (ΔePVS%), difference in central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO₂), and lactate clearance rate (LCR) were calculated. Patients were divided into sepsis group and septic shock group based on the diagnosis at ICU admission, and septic patients were subdivided into survival group and death group based on their 28-day survival status. The differences in clinical data between the groups were compared. The correlation between ePVS or ΔePVS% and volume status related indicators during early liquid resuscitation was analyzed by Spearman rank sum correlation test. The predictive value of each variable for 28-day survival in patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve), and 28-day death risk factors were analyzed by Logistic regression method. RESULTS: Fifty-four septic patients were enrolled in the final analysis, including 17 with sepsis and 37 with septic shock; 34 survived at 28 days and 20 died, with a 28-day survival rate of 63.0%. Compared with the sepsis group, the septic shock group had a lower venous ePVS at ICU admission [dL/g: 4.96 (3.67, 7.15) vs. 7.55 (4.36, 10.07), P < 0.05]. Compared with the death group, the survival group had higher T6h arterial and venous ΔePVS%, and albumin [Alb; T6h arterial ΔePVS% (%): 11.57% (-1.82%, 31.35%) vs. 0.48% (-5.67%, 6.02%), T6h venous ΔePVS%: 9.62% (3.59%, 25.75%) vs. 1.52% (-9.65%, 7.72%), Alb (g/L): 27.57±4.15 vs. 23.77±6.97, all P < 0.05], lower SOFA score, APACHE II score, AST, T0h Lac, and T3h and T6h norepinephrine dosage [SOFA score: 9.00 (8.00, 10.00) vs. 11.50 (9.25, 14.50), APACHE II score: 18.00 (14.75, 21.25) vs. 25.50 (21.00, 30.00), AST (U/L): 34.09 (23.20, 56.64) vs. 79.24 (25.34, 196.59), T0h Lac (mmol/L): 1.75 (1.40, 2.93) vs. 3.25 (2.33, 5.30), norepinephrine dosage (mg): 0.98 (< 0.01, 3.10) vs. 4.60 (1.05, 8.55) at T3h, 1.82 (0.38, 5.30) vs. 8.20 (2.80, 17.73) at T6h, all P < 0.05]. While there were no significantly differences in other basic data and ePVS at all of the time points before and after resuscitation between the two groups. Correlation analysis showed that T6h venous ePVS was significantly positively correlated with T6h IVC variability in septic patients (r = 0.360, P < 0.05), T0h arterial ePVS was significantly negatively correlated with T3h and T6h liquid intake volume (r₁ = -0.367, r₂ = -0.280, both P < 0.05), and venous ePVS at ICU admission was significantly positively correlated with NT-proBNP at ICU admission (r = 0.409, P < 0.05). T6h venous ΔePVS% was significantly positively correlated with T3h liquid intake volume and T6h LCR (r₁ = 0.286, r₂ = 0.286, both P < 0.05), and significantly negatively correlated with T6h urine volume and T6h change value of Pcv-aCO₂ (ΔPcv-aCO₂; r₁ = -0.321, r₂ = -0.371, both P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of T6h venous ΔePVS% for predicting 28-day survival in septic patients was 0.726 [95% confidence interval (95%CI) was 0.578-0.875, P = 0.006], with a sensitivity of 82.4%, a specificity of 60.0%, and an optimal cut-off value of 3.09%. Binary multifactorial Logistic regression analysis showed that an increase in T6h venous ΔePVS% was a protective factor for 28-day death in patients with sepsis on early fluid resuscitation [odds ratio (OR) = 0.900, 95%CI was 0.834-0.972, P = 0.007]. CONCLUSIONS ePVS may have potential for assessing the volume status of septic patients during early fluid resuscitation. The ΔePVS% during early fluid resuscitation may help to identify septic patients with a poor prognosis.
Humans ; Prognosis ; Fluid Therapy ; Sepsis/physiopathology* ; Prospective Studies ; Plasma Volume ; Intensive Care Units ; Resuscitation ; Male ; Female ; Middle Aged ; Shock, Septic/therapy*

Congenital hyperinsulinism is the most common cause of hypoglycemia in children, characterized by a complex genetic basis, diverse pathogenic mechanisms, and significant clinical heterogeneity.Delayed diagnosis and treatment can lead to irreversible neurological sequelae, including epilepsy and psychomotor retardation.In this review, recent advancements in the molecular genetics, imaging localization, therapeutic strategies, and follow-up outcomes of congenital hyperinsulinism were summarized so as to offer valuable insights for its clinical management.