Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To explore characteristics of co-infection of Chlamydia pneumoniae(Cpn)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and identify their effect on SARS-CoV-2-induced inflammatory response.Methods Patients with coronavirus disease 2019(COVID-19)who received treatment in a hospital in Chenzhou City from December 20,2022 to February 20,2023 were selected.According to the severity of COVID-19,severe and critical cases were classified as the severe symptom group,while mild and moderate cases were classified as the mild symptom group.Meanwhile,according to the age of patients(≥18 years old as adults,＜18 years old as juveniles),they were divided into the adult severe symptom group,adult mild symptom group,juvenile severe symptom group,and juvenile mild symptom group.Propensity score was adopted to match age,gender,and under-lying diseases of patients in severe symptom and mild symptom group in a 1∶1 ratio.Bronchoalveolar lavage fluid(BALF),throat swabs,and serum specimens of patients were collected.Cpn IgG/IgM antibody was detected by enzyme-linked immunosorbent assay(ELISA),levels of 12 common cytokines(including interleukin-8[IL-8])in BALF were detected by flow cytometry,differences among groups were compared.Results A total of 102 patients were included,with 61 severe and critical(severe symptom)patients,as well as 41 mild and moderate(mild symp-tom)patients.There were 71 patients aged ≥18 years and 31 juvenile patients aged＜18 years.There were 39 pa-tients in the adult severe symptom group and 32 in the adult mild symptom group,and 30 pairs were successfully matched through propensity score analysis.There were 22 patients in the juvenile severe symptom group and 9 in the juvenile mild symptom group,and 8 pairs were successfully matched through propensity score analysis.Among COVID-19 patients,the positive rates of Cpn IgG and IgM were 36.27％(n=37)and 8.82％(n=9),respective-ly,with 1 case positive for both Cpn IgG and IgM.The level of interferon(IFN)-α in serum specimens from adult patients with severe symptom combined with positive Cpn IgG was higher than that of IgG negative patients(P=0.037).There was no statistically significant difference in the levels of other cytokines in BALF and serum speci-mens between the two groups of patients(all P＞0.05).The levels of IL-8 and IL-17 in serum specimens of patients with positive Cpn IgG in the adult mild symptom group were both higher than those in Cpn IgG negative patients(both P＜0.05).The levels of IL-8 in both BALF and serum specimens from Cpn IgM positivity patients in the ju-venile mild symptom group were higher than those from patients with negative Cpn IgM(both P＜0.05).Logistic regression analysis results showed that Cpn IgG and IgM positivity were not risk factors for the development of se-vere COVID-19.Conclusion Combined Cpn infection is not a risk factor for the development of severe symptom in COVID-19 patients,and Cpn infection has limited impact on the secretion of inflammatory factors caused by SARS-CoV-2.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of hyperoside,kaempferol-3-O-rutinoside,esculin,chlorogenic acid,berberine,quercetin,rehmannioside D,palmatine,leonurin A,paeoniflorin,timosaponin BⅡand rutin in Guanhuangmu Granules.METHODS The analysis was performed on a 40℃ thermostatic Acquity UPLC HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.05%formic acid(containing 2 mmol/L ammonium acetate)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.RESULTS Twelve constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 93.46%-102.01%with the RSDs of 2.13%-3.65%.CONCLUSION This rapid,accurate,stable and sensitive method can be used for the quality control of Guanhuangmu Granules.

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1β(IL-1β) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1β showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.
Rats ; Animals ; Chondrocytes ; Osteoarthritis, Knee/pathology* ; RNA, Circular/pharmacology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; MicroRNAs/metabolism* ; Apoptosis ; Autophagy/genetics* ; Collagen/metabolism*