ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

OBJECTIVE To provide standardized guidance for the homogenization construction and management of pharmaceutical care in urban medical groups. METHODS This consensus was jointly initiated by the Therapeutic Drug Monitoring Professional Committee of the Chinese Pharmacological Society and the Expert Committee on Precision Clinical Medication of the Guangdong Pharmaceutical Association. Led by Guangzhou Red Cross Hospital， a drafting group of 7 members and an expert group of 36 members were organized. The outline of the Expert Consensus on Homogeneous Construction and Management of Pharmaceutical Care in Urban Medical Groups （hereinafter referred to as the “Consensus”） was discussed and finalized using the nominal group technique， and a preliminary draft was formed. The Delphi method was used for online c orrespondence review， and 12 external experts were invited for evaluation. After analyzing and revising expert opinions， the final Consensus was formed. RESULTS &CONCLUSIONS This Consensus defines the position setting and appointment procedures for the chief pharmacist， and establishes a three-tier professional guidance network of “chief pharmacist-regional/specialist pharmacist-pharmaceutical liaison of member institutions”. It formulates unified management standards for the drug supply catalog， establishes a full-process homogenization mechanism for prescription review， prescription commentation and comprehensive pharmaceutical care， and specifies the core functions and performance requirements of the prescription review system. It also supports by long-term mechanisms including cost allocation and performance assessment. This consensus can serve as a systematic reference for the homogeneous construction and management of pharmaceutical care systems in urban medical groups.

Objective:To explore the value of high resolution computed tomography（HRCT） combined with Magnetic Resonance Imaging（MRI） in the diagnosis of inner ear malformation. Methods:HRCT and MRI data of 82 patients with inner ear malformations were analyzed retrospectively. HRCT MPR and CPR reconstruction of the inner ear structure, facial nerve canal and oblique sagittal MRI reconstruction of the internal auditory canal were performed. The inner ear malformations were classified, the conditions of facial nerve canal and cochlear nerve were evaluated. The association between inner ear malformation and cochlear nerve dysplasia were analyzed by Chi-square test with continuity correction. Results:Among the 82 patients with inner ear malformations,there were 49 cases of bilateral symmetry, 11 cases of bilateral asymmetry and 22 cases of unilateral inner ear malformations. Respectively, the most prevalent types were IP-Ⅱ（42.96%）, dilatation of atrium aqueduct（18.31%） and malformations of atrium and semicircular canal 19.72%. Out of 50 cases of cochlear malformations,only 3 were isolated cochlear malformations, and the rest were accompanied by other malformations of varying degrees. In the 67 ears examined by MRI, 26（38.81%） had cochlear nerve deficiency（CND）, and the incidence of CND varied with different types of inner ear malformations. Out of 142 ears, 28（19.72%） had abnormalities of the facial nerve canal. Conclusion:HRCT combined with MRI can accurately distinguish the types of inner ear malformation and effectively evaluate the facial nerve canal and cochlear nerve, and further provides the important finger and Guide value for the clinician to formulate the reasonable treatment and the operation plan.
Humans ; Ear, Inner/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Female ; Male ; Tomography, X-Ray Computed/methods* ; Child ; Adolescent ; Adult ; Child, Preschool ; Cochlear Nerve/diagnostic imaging* ; Facial Nerve/abnormalities* ; Cochlea/abnormalities* ; Infant ; Young Adult

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

OBJECTIVE: To explore clinical effective and safety of subarachnoid block (SA), adductor canal block (ACB), and femoral nerve block (FNB) for early analgesia in anterior cruciate ligament (ACL) reconstruction. METHODS: From September 2022 to October 2023, 90 patients with ACL rupture who received unilateral knee arthroscopic ACL reconstruction were selected and divided into ACB group, FNB group and SA group according to different anesthesia methods, with 30 patients in each group. There were 12 males and 18 females in ACB group, aged from 18 to 60 years old with an average of (33.3±13.8) years old;14 patients with gradeⅠand 16 patients with gradeⅡaccording to American Society of Aneshesiologists (ASA);13 patients on the left side and 17 patients on the right side. There were 15 males and 15 females in FNB group, aged from 18 to 60 years old with an average of (33.5±12.9) years old;15 patients with gradeⅠand 15 patients with gradeⅡ;16 patients on the left side and 14 patients on the right side. There were 16 males and 14 females in SA group, aged from 18 to 60 years old with an average of (31.0±12.6) years old;18 patients with grade I and 12 patients with gradeⅡ;17 patients on the left side and 13 patients on the right side. In ACB and FNB groups, the nerve block of ACB and FNB were performed under ultrasound guidance before SA anesthesia with 15 ml of 0.3% ropivacaine. Visual analogue scale (VAS) and quadriceps muscle strength at rest and passive movement were recorded and compared among 3 groups at 4, 8, 12, 16, 24 and 48 h after operation, as well as the dosage of tramadol injection analgesics, incidence of nausea and vomiting, nerve block time and other complications within 48 h after operation were compared. RESULTS: All patients were followed up for 11 to 20 (15.8±2.4) months. VAS at 4, 8, 12, 16, 24 and 48 h after operation of SA group was significantly higher than that of ACB and FNB groups, with statistical significance (P<0.05). There were no significant difference in VAS of rest and passive movement at 4, 8, 12, 16, 24 and 48 h after operation between ACB group and FNB group(P>0.05). At 4, 8, 12 and 16 h after operation, the quadriceps muscle strength in SA and ACB groups was higher than that in FNB group, with statistical significance (P<0.05);but there was no statistical significance in quadriceps muscle strength among three groups at 24 and 48 h after operation(P>0.05). One patient occurred nausea and vomiting in ACB group, 2 patients in FNB group and 5 patients in SA group, and no significant difference among three groups (χ²=0.352, P=0.171). The dosage of tramadol in SA group was (300.00±136.50) mg, which was higher than that in FNB group (168.33±73.70) mg and ACB(163.33±70.70) mg, and the difference was statistically significant (P<0.05). There was no significant difference in nerve block time between ACB group and FNB group (t=1.964, P=0.054). There was no puncture site bleeding, local anesthesia drug poisoning and hematoma formation among three groups. CONCLUSION Both FNB and ACB could provide good early analgesia after ACL reconstruction, but ACB group has little effect on quadriceps muscle strength. Patients could have early postoperative functional training without pain, which is more beneficial to the recovery of knee joint function, and could reduce the use of analgesic drugs, without serious complications, which is safe and reliable method.
Humans ; Male ; Female ; Nerve Block/methods* ; Adult ; Anterior Cruciate Ligament Reconstruction ; Adolescent ; Middle Aged ; Young Adult ; Analgesia/methods* ; Pain, Postoperative/drug therapy* ; Femoral Nerve

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

OBJECTIVES: To develop a scale for evaluating responsive feeding behaviors among caregivers of children aged 0-24 months in China, and to examine its reliability and validity. METHODS: An initial item pool was constructed through literature review, expert panel discussions, and caregiver interviews. Items were screened and revised using expert consultation and item analysis. A total of 523 caregivers of children aged 0-24 months were randomly selected from urban community health service centers in Nanjing for a formal survey to assess the scale's reliability and validity. RESULTS: The scale comprised two age-specific subscales: 0-6 months (4 dimensions, 18 items) and 7-24 months (5 dimensions, 29 items). Cronbach's alpha values for the two subscales were 0.766 and 0.850, respectively; split-half reliability coefficients were 0.616 and 0.716. Content validity indices were 0.83 for the 0-6 months subscale and 0.86 for the 7-24 months subscale. Confirmatory factor analysis supported the structural validity of both subscales, with all fit indices within acceptable ranges. CONCLUSIONS The two age-specific subscales demonstrate good reliability and validity and can serve as practical tools for assessing caregivers' responsive feeding behaviors in children aged 0-24 months, suitable for clinical application and dissemination.
Humans ; Infant ; Caregivers/psychology* ; Male ; Female ; Feeding Behavior ; Child, Preschool ; Infant, Newborn ; Reproducibility of Results

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

OBJECTIVE To discuss the clinical application effect of free transplantation with anterolateral thigh flap repairing tissue defects after resection of head and facial tumors.METHODS A retrospective analysis was conducted on the patients from August 2018 to November 2023,diagnosed with head and facial tumors who underwent surgical resection and simultaneous repair with free anterolateral thigh flaps in Department of Burns and Plastic Surgery at the North District of Shanghai 9th People's Hospital,Shanghai Jiao Tong University School of Medicine.The survival of flaps and the healing of the donor site were observed,and postoperative follow-up was conducted for 6-12 months.The texture of flaps,scar formation in the surgical area,tumor recurrence,and patient satisfaction were evaluated.The Karnofsky Performance Status(KPS)scale was used to assess the patients'health status preoperatively and at the final postoperative follow-up.RESULTS 16 patients were enrolled,comprising 12 males and 4 females,aged from 31 to 67 years old.Pathological types of tumors included 9 cases squamous cell carcinoma,4 cases dermatofibrosarcoma protuberans,and 3 cases other malignancies.All 16 flaps survived completely.The follow-up period was 6-12 months,and the texture of flaps was good.All patients were satisfied with the surgical effect,and no tumor recurred.All incisions in the thigh donor area healed in one stage,and linear scars were observed during follow-up.The preoperative KPS score was 80±7.30,while the postoperative KPS score at the final follow-up was 88.13±6.55,showing a statistically significant difference(t=4.96,P<0.01).CONCLUSION Free transplantation of the anterolateral thigh flap is a reliable and effective method for patients with large-scale soft tissue defects after resection of head and facial tumors.