In 1861, the missionary William Lockhart founded the Peking Hospital in Beijing. From 1861 to 1863, William Lockhart not only cured a large number of patients in the Peking Hospital but also introduced western surgical techniques, hygiene and disinfection concepts, and medical record management systems. During its operation, the Peking Hospital's unique value can be seen in its sources and modes of financing, scope of services, number of patients treated, and missionary functions. The Peking Hospital served as a vital bridge for the exchange of medical knowledge between the East and the West, and it played a pivotal role in transforming China's modern medical system and modern health concepts, exerting a profound influence on the development of modern medicine.

Objective:To investigate the clinical manifestations and genetic characteristics of a Chinese Han family with Axenfeld-Rieger syndrome (ARS).Methods:A pedigree study was conducted.Three people from a Chinese Han family with ARS who visited Henan Eye Hospital in January 2024 were included, including 1 patient.Clinical data of the proband and her parents were collected.Comprehensive ophthalmic examination and general physical examination were performed on the proband and her parents.Peripheral blood samples were obtained from family members for DNA extraction.Whole exome sequencing was performed on the proband, and the copy number of the ZBED1P1, ENPEP, PITX2, and FAM241A genes in family members were validated using the real-time fluorescent quantitative PCR.Axenfeld-Rieger syndrome, Axenfeld-Rieger Syndrome, and PITX2 were used as keywords to search across databases such as OMIM, ClinVar, PubMed, CNKI, Wanfang, VIP, DECIPHER, and Google Scholar.The clinical manifestations and microdeletion types of different patients in ARS literature related to PITX2 microdeletions in China population were summarized, and the relationship between genotype and clinical phenotype was analyzed.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2024[34]).All subjects understood the purpose of the study and voluntarily signed the informed consent form. Results:The proband was a 25-year-old female, exhibiting diminutive cornea in both eyes, polycoria, deformation and displacement of pupils, a flat mid-face, maxillary dysplasia, tooth loss, and a protruding umbilicus, among other symptoms.Parents of the proband were phenotypically normal.DNA sequencing identified a 1.06 MB microdeletion on chromosome 4q25 in the proband.Real-time quantitative PCR confirmed that this microdeletion encompassed the PITX2 and ENPEP genes, and it was absent in the proband's parents.The ClinGen CNV pathogenicity scoring indicated that the deletion involving the PITX2 gene represented a novel pathogenic copy number variation (CNV).Five studies related to 4q25 microdeletion in Chinese families with Axenfeld-Rieger syndrome was screened, including 13 patients.Clinical manefestations of the 13 patients included corneal disorders (accounting for 100%), umbilical hernia and dental anomalies (accounting for 92%), irregular intraocular pressure (accounting for 62%), iris atrophy (accounting for 46%), and posterior corneal embryotoxon (accounting for 31%). Conclusions:For this Chinese family diagnosed with ARS, a novel pathogenic 4q25 microdeletion variant encompassing the PITX2 gene was found in the proband, which is associated with characteristic phenotypes including microcornea, congenital iris dysplasia, polycoria, tooth loss, and a protruding umbilicus.

Objective:To investigate the clinical manifestations and genetic characteristics of a Chinese Han family with Axenfeld-Rieger syndrome (ARS).Methods:A pedigree study was conducted.Three people from a Chinese Han family with ARS who visited Henan Eye Hospital in January 2024 were included, including 1 patient.Clinical data of the proband and her parents were collected.Comprehensive ophthalmic examination and general physical examination were performed on the proband and her parents.Peripheral blood samples were obtained from family members for DNA extraction.Whole exome sequencing was performed on the proband, and the copy number of the ZBED1P1, ENPEP, PITX2, and FAM241A genes in family members were validated using the real-time fluorescent quantitative PCR.Axenfeld-Rieger syndrome, Axenfeld-Rieger Syndrome, and PITX2 were used as keywords to search across databases such as OMIM, ClinVar, PubMed, CNKI, Wanfang, VIP, DECIPHER, and Google Scholar.The clinical manifestations and microdeletion types of different patients in ARS literature related to PITX2 microdeletions in China population were summarized, and the relationship between genotype and clinical phenotype was analyzed.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2024[34]).All subjects understood the purpose of the study and voluntarily signed the informed consent form. Results:The proband was a 25-year-old female, exhibiting diminutive cornea in both eyes, polycoria, deformation and displacement of pupils, a flat mid-face, maxillary dysplasia, tooth loss, and a protruding umbilicus, among other symptoms.Parents of the proband were phenotypically normal.DNA sequencing identified a 1.06 MB microdeletion on chromosome 4q25 in the proband.Real-time quantitative PCR confirmed that this microdeletion encompassed the PITX2 and ENPEP genes, and it was absent in the proband's parents.The ClinGen CNV pathogenicity scoring indicated that the deletion involving the PITX2 gene represented a novel pathogenic copy number variation (CNV).Five studies related to 4q25 microdeletion in Chinese families with Axenfeld-Rieger syndrome was screened, including 13 patients.Clinical manefestations of the 13 patients included corneal disorders (accounting for 100%), umbilical hernia and dental anomalies (accounting for 92%), irregular intraocular pressure (accounting for 62%), iris atrophy (accounting for 46%), and posterior corneal embryotoxon (accounting for 31%). Conclusions:For this Chinese family diagnosed with ARS, a novel pathogenic 4q25 microdeletion variant encompassing the PITX2 gene was found in the proband, which is associated with characteristic phenotypes including microcornea, congenital iris dysplasia, polycoria, tooth loss, and a protruding umbilicus.

Objective To investigate the effect of BIS-guided closed-loop target-controlled infusion on perioperative Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy under different anesthesia and sedation depths. Methods We applied random number table method to divide 73 elderly patients undergoing elective laparoscopic radical gastrectomy into BIS closed-loop target-controlled infusion group with BIS value of 55(group H, n=36) and BIS value of 45(group L, n=37).Intravenous blood samples were collected immediately before surgery (T1), 2h after surgery (T2), 24h after surgery (T3) and 72h after surgery (T4).IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were determined by flow cytometry microsphere array.We compared operation duration, postoperative PACU stay time and postoperative hospitalization time between two groups. Results Compared with T1, IL-6 and IL-10 concentration in group H at T2, T3 and T4 significantly increased (P < 0.05), IL-4 and TNF-α in group H at T4 were significantly increased (P < 0.05), IL-2 and IFN-γ in group H at T2 and T4 were significantly increased (P < 0.05), the concentration of IL-6 and IL-10 in group L at T2, T3 and T4 were increased (P < 0.05), IL-2 in group L at T4 was decreased (P < 0.05), and IFN-γ/IL-6 in two groups were decreased at T2, T3 and T4(P < 0.05).Compared with group L, IL-6 and IL-10 in group H were significantly increased at T2(P < 0.05), IFN-γ/IL-6 in group H was significantly decreased (P < 0.05), IL-2 and IL-10 in group H were significantly increased at T4(P < 0.05).Operation duration, postoperative PACU stay time and postoperative hospitalization time had no statistical significance between two groups (P > 0.05). Conclusion The anesthesia and sedation depth of BIS-guided closed-loop target-controlled infusion set at 45 is better than 55 in maintaining Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy, but it has no obvious effect on long-term prognosis.

Background: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. Methods: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. Results: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. Conclusions Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

Background: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. Methods: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. Results: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. Conclusions Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

Remimazolam is a new ultra-short-acting sedative, with rapid onset and recovery, metabolism independent of liver and kidney function, light respiratory inhibition, stable hemodynamics, long time application without accumulation. Carboxylic acid metabolites have no pharmacological effects, and can be rapidly reversed by antagonist flumazenil, which is expected to become a new choice of clinical sedative. In this paper, pharmacological characteristics and recent research progress of remimazolam are reviewed, which can provide reference for clinical safe drug use.

Objective To evaluate the effect of epidural block on postoperative cognitive dysfunction in elderly patients undergoing laparoscopic radical operation for gastric cancer under general anesthesia.Methods Sixty ASA physical status Ⅰ or Ⅱ patients,aged 65-75 yr,with preoperative Mini-Mental State Examination (MMSE) score ＞ 23,scheduled for elective laparoscopic radical operation for gastric cancer under general anesthesia,were randomized into epidural block group (group E,n =30) and control group (group C,n =30) using a random number table.Epidural block was performed at T8,9 interspace before induction of anesthesia.Anesthesia was induced with iv injection of midazolam 0.03 mg/kg,propofol 1.0-1.5 mg/kg,fentanyl 3-4 μg/kg and rocuronium 0.9 mg/kg.The patients were endotracheally intubated and mechanically ventilated.Anesthesia was maintained with iv infusion of remifentanil 0.15-0.25 μg· kg-1· min 1 and propofol target-controlled infusion (target plasma concentration 2.5-3.0μg/ml).In group E,10 ml of mixture of 0.25％ ropivacaine and 0.04 mg/ml butorphanol was injected via the epidural catheter at 30 min before skin incision.In the two groups,the mixture 10 ml mentioned above was administered via the epidural catheter at 10 min before the end of operation followed by patientcontrolled epidural analgesia.The development of postoperative cognitive dysfunction (MMSE score ＜ 21) was recorded within 72 h after operation.Blood samples were collected from the internal jugular vein to detect the concentration of serum protein S-100β.Results The concentration of serum protein S-100β was significantly lower at 6,12 and 24 h after operation,and the incidence of postoperative cognitive dysfunction within 72 h after operation was lower in group E than in group C (P ＜ 0.05).Conclusion Epidural block can decrease the development of postoperative cognitive dysfunction in elderly patients undergoing laparoscopic radical operation for gastric cancer under general anesthesia.

Objective To investigate the effects of positive end-expiratory pressure (PEEP) after recruitment maneuvers (RM) on respiratory mechanics and gas exchange during laparoscopy in obese patients.Methods Sixty-three ASA physical status Ⅱ or Ⅲ patients,aged 42-64 yr,with body mass index 30-40kg/m2,were randomly allocated into 3 groups (n=21 each):PEEP0 group,PEEP5 group and PEEP10 group.PEEP was not given after RM in PEEP0 group.In PEEP5 and PEEP10 groups,a recruiting maneuver was followed by PEEP 5 and 10 cm H2 O,respectively,until the end of pneumoperitoneum.The intraabdominal pressure was set at 12mmHg in the three groups.Parameters of respiratory mechanics including peak airway pressure (Ppeak),airway plateau pressure (Peat),chest wall plateau pressure (PplatCW),airway resistance (Raw),elastance of respiratory system (ERS),elastanc of chest wall (ECW) and elastance of lung (EL) and parameters of gas exchange including oxygenation index (PaO2/FiO2),arterial to end-tidal difference in carbon dioxide (Da-ETCO2),alveolar-arterial oxygen tension difference (DA-aO2),and dead space/tidal volume ratio (VD/VT) were measured before pneumoperitoneum (T0),at 20 min of pneumoperitoneum (T1),at 10 min after the end of recruitment (T2),and at the end of pneumoperitoneum (T3).Results Da-ETCO2,ERS and Raw were decreased at T2,ECW and EL were decreased at T3 in PEEP5 group,and Da-ETCO2,VD/VT,DA-aO2,Pplatcw Raw and EL were decreased at T2.3,and PaO2/FiO2 was increased at T2,ECW was decreased at T3 in group PEEP10 as compared with that in group PEEP0 (P ＜ 0.05).Da-ETCO2 and VD/VT were decreased and PaO2/FiO2 was increased at T2,3,Raw was increased and EL was decreased at T2 in group PEEP10 as compared with that in group PEEP5 (P ＜ 0.01).Conclusion PEEP after RM can improve respiratory mechanics and gas exchange during laparoscopy in obese patients and PEEP maintained at 10 cm H2O after RM provides better efficacy than PEEP at 5 cm H2 O.

Objective To evaluate the effects of different doses of dexmedetomidine on propofol-induced inhibition of responses to laryngeal mask airway (LMA) insertion when combined with fentanyl in patients undergoing gynecological operation.Methods One hundred and twenty-five ASA Ⅰ-Ⅱ female patients,aged 20-60 yr,scheduled for elective short-time surgery,were randomly divided into 5 groups (n =25 each):normal saline group (group NS) and different doses of dexmedetomidne groups (groups D1-4).Normal saline 40 ml and dexmedetomidne 0.4,0.6,0.8,1.0 μg/kg (in 40 ml of normal saline) were infused over 10 min in groups NS and D1-4,respectively.1％ propofol was then given by target-controlled infusion.The concentration of propofol was determined by using modified Dixon's up-and-down method.The initial plasma concentration of propofol was 3.0 μg/ml and the ratio between the 2 successive concentrations was 1.1.Fentanyl 1.5 μg/kg was injected intravenously when the effect-site concentration of propofol reached the preset plasma concentration.LMA was inserted 4 min later.When LMA insertion was successful,the concentration of propofol was decreased in the next patient and when LMA insertion failed,the concentration of propofol was increased in the next patient.Failure of LMA insertion was defined as difficulty in inserting LMA or body movement,corner of mouth movement,biting LMA,swallowing and/or lacrimation during insertion.The median effective target effect-site concentration and 95％ confidence interval of propofol blunting responses to LMA insertion when combined with fentanyl were calculated.Results The median effective target effect-site concentration (95％ confidence interval) of propofol blunting responses to LMA insertion when combined with fentanyl were 3.09 (2.83-3.36),2.48 (2.26-2.73),2.29 (2.18-2.41),2.04 (1.95-2.12) and 1.67 (1.55-1.81) μg/ml in groups NS and D1 4,respectively.Conclusion Dexmedetomidine can enhance propofol-induced inhibition of responses to LMA insertion when combined with fentanyl in dose-dependent manner in patients undergoing gynecological operation.