Based on the clinical thinking of combining diseases and patterns， we combined disease identification， pattern differentiation， and constitution identification， and put forward the theory of identifying and treating critical hypertension， which is "examining the symptoms first， identifying the constitutions as reference， and combining the diseases and patterns". Firstly， the starting point of identifying the disease is to examine the symptoms， and those with precise diagnosis and strong specificity will be diagnosed with the disease， while those with relatively broad diagnosis and fuzzy characteristics will be emphasised on identifying constitutions and differentiating patterns. Focusing on the impact of constitution identification on disease identification and pattern differentiation， constitution identification could be the basis when no symptoms to identify， and based on the theory of "constitution-disease correlation" and "constitution-pattern correlation" to improve the understanding of borderline hypertension from the group and individual level， which helps to identify and predict the development of the diseases and patterns； if the symptoms are complicated and difficult to identify， it is necessary to take syndrome as the outline， use the syndrome to unify the disease， and then refer to the constitution to legislate and prescribe medications. This paper summarizes the traditional Chinese medicine clinical differentiation and treatment strategy of borderline hypertension clear and easy to grasp， with a view to provide a feasible and efficient reference for prevention and treatment of borderline hypertension with traditional Chinese medicine.

Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.

Objective To investigate the mechanism underlying the neuroprotective effect of linarin(LIN)against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury(SCI).Methods Fifty C57BL/6J mice(8-10 weeks old)were randomized to receive sham operation,SCI and linarin treatment at 12.5,25,and 50 mg/kg following SCI(n=10).Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale,inclined plane test,and footprint analysis,and spinal cord tissue damage and myelination were evaluated using HE and LFB staining.Nissl staining,immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue.In cultured BV2 cells,the effects of linarin against lipopolysaccharide(LPS)-induced microglia activation,inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining,Western blotting,RT-qPCR,and ELISA.In a BV2 and HT22 cell co-culture system,Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation.Results Linarin treatment significantly improved locomotor function(P<0.05),reduced spinal cord damage area,increased spinal cord myelination,and increased the number of motor neurons in the anterior horn of the SCI mice(P<0.05).In both SCI mice and cultured BV2 cells,linarin effectively inhibited glial cell activation and suppressed the release of iNOS,COX-2,TNF-α,IL-6,and IL-1β,resulting also in reduced neuronal apoptosis in SCI mice(P<0.05).Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF-κB signaling pathway.In the cell co-culture experiments,linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells(P<0.05).Conclusion The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF-κB signaling pathway,which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.

Objective To investigate the mechanism underlying the neuroprotective effect of linarin(LIN)against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury(SCI).Methods Fifty C57BL/6J mice(8-10 weeks old)were randomized to receive sham operation,SCI and linarin treatment at 12.5,25,and 50 mg/kg following SCI(n=10).Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale,inclined plane test,and footprint analysis,and spinal cord tissue damage and myelination were evaluated using HE and LFB staining.Nissl staining,immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue.In cultured BV2 cells,the effects of linarin against lipopolysaccharide(LPS)-induced microglia activation,inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining,Western blotting,RT-qPCR,and ELISA.In a BV2 and HT22 cell co-culture system,Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation.Results Linarin treatment significantly improved locomotor function(P<0.05),reduced spinal cord damage area,increased spinal cord myelination,and increased the number of motor neurons in the anterior horn of the SCI mice(P<0.05).In both SCI mice and cultured BV2 cells,linarin effectively inhibited glial cell activation and suppressed the release of iNOS,COX-2,TNF-α,IL-6,and IL-1β,resulting also in reduced neuronal apoptosis in SCI mice(P<0.05).Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF-κB signaling pathway.In the cell co-culture experiments,linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells(P<0.05).Conclusion The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF-κB signaling pathway,which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.

A 60-year-old female proband presented with recurrent erythema, blisters and erosions all over the body for 30 years, which had been aggravated 10 days prior to the presentation. Skin examination showed erythematous swelling of the bilateral eyelids with scattered dark red crusts, scattered erythema and erosions on the nasolabial folds and chin, large areas of erythema and erosions on the neck, bilateral axillae, left cubital fossa, perineum and perianal area, accompanied by bright red granulation tissues and positive Nikolsky′s sign. The proband had two sons, both of whom occasionally presented with erythema and erosions on the axillae and groin, and had not been diagnosed or treated. Blood samples were collected from the proband and her two sons, and genomic DNA was extracted and subjected to whole-exome sequencing. A heterozygous deletion mutation c.955_957del (p.A319del) was identified in the ATP2C1 gene in the proband and her two sons, which had not been previously reported. The patient was finally diagnosed with generalized familial benign chronic pemphigus.

OBJECTIVE To develop a whole-process intelligent model of pharmaceutical care for peritoneal dialysis （PD） patients， and to provide a reference for clinical pharmacists to provide standardized PD pharmaceutical care. METHODS The pharmaceutical care mode of PD patients at home and abroad was investigated and analyzed. Based on the actual situation of the First Affiliated Hospital of Soochow University （hereinafter referred to as “our hospital”）， with “home→PD center outpatient→ inpatient department” as the main node， the recycling process of medication reconciliation was optimized. The whole-process intelligent pharmaceutical care model of PD was illustrated by improving the Chinese version of the drug-related problems （DRPs） classification tool， developing the corresponding pharmaceutical care process， and presenting specific cases. RESULTS Based on the medication therapy management （MTM） platform， our hospital had built a closed-loop PD whole-process intelligent pharmaceutical care model of “in-hospital pharmaceutical care （building document）-PD outpatient MTM-home pharmaceutical care （online App management）”. A “double cycle” workflow of “admission→discharge→outpatient” medication reconciliation cycle and “discovery-analysis-intervention-follow-up-record-evaluation” DRPs cycle was formed. CONCLUSIONS The establishment of the whole-process intelligent pharmaceutical care model for PD in our hospital provides experience for standardizing pharmaceutical care for PD patients， and can reduce DRPs.

OBJECTIVE: To investigate the incidence and infection regularity of ventilator-associated pneumonia (VAP) in patients undergoing tracheal intubation and to provide reference for the prevention and treatment of VAP infection in the future. METHODS: A retrospective study was conducted to collect the microbial data of airway secretion cultures from 72 patients with endotracheal intubation admitted to the emergency ward of Shanghai Fifth People's Hospital from May 2020 to February 2021, and the species of microorganisms and intubation time were statistically analyzed. RESULTS: Among 72 patients with endotracheal intubation, males were more than females (58.33% vs. 41.67%); Patients over 60 years old accounted for 90.28%; pneumonia was the main primary disease, accounting for 58.33%. Pathogenic tests showed that: (1) 72 patients were infected with Acinetobacter baumannii (AB), Klebsiella pneumoniae (KP), and Pseudomonas aeruginosa (PA) 48 hours after intubation, 51.39% (37/72), 27.78% (20/72), and 26.39% (19/72), respectively. The infection rate of AB was significantly higher than that of KP and PA. Within 48 hours of intubation, the infection rates of AB, KP, and PA were 20.83% (15/72), 13.89% (10/72), and 4.17% (3/72), respectively. Of the 42 patients with primary pneumonia, 61.90% (26/42) were infected with one or more of the three pathogenic bacteria AB, KP, and PA 48 hours after intubation, indicating a change in the etiology of the pathogenic bacteria, with the main pathogenic bacteria transitioning from other pathogenic bacteria to AB, KP, and PA. (2) AB, KP, and PA were prone to cause late onset VAP (i.e., intubation ≥ 5 days). Respectively, among VAP patients infected with AB, late onset VAP accounted for 59.46% (22/37). Among patients infected with KP, 75.00% (15/20) had late onset VAP. Among patients infected with PA, late onset VAP accounted for 94.74% (18/19), indicating a higher proportion of late onset VAP caused by PA and KP. (3) Infection was closely related to intubation time, and the pipeline can be replaced according to the peak period of infection. AB and KP infections peaked within 4 days after intubation, reaching 57.69% (30/52) and 50.00% (15/30), respectively. It is recommended to replace the tubes or undergo sensitive antimicrobial therapy around 3-4 days after starting the machine. The proportion of PA infection after 7 days of intubation was 72.73% (16/22), and it was considered to replace the pipeline after 7 days. (4) Most of the three pathogenic bacteria, AB, KP, and PA were carbapenem resistant pathogens with multiple drug resistance. Except for PA, the infection rate of carbapenem resistant bacteria (CRAB, CRKP) was significantly higher than that of non-carbapenem resistant bacteria (AB, KP), accounting for 86.54% (45/52) and 66.67% (20/30) of the corresponding infection cases, respectively, while CRPA only accounts for 18.18% (4/22). CONCLUSIONS The main differences in VAP infection caused by AB, KP, and PA pathogens are infection time, infection probability, and carbapenem resistance. Targeted prevention and treatment measures can be implemented for patients with intubation.
Female ; Male ; Humans ; Middle Aged ; Pneumonia, Ventilator-Associated ; Retrospective Studies ; China ; Intubation, Intratracheal ; Acinetobacter baumannii ; Klebsiella pneumoniae

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Objective To explore the short-term efficacy in children with head and neck rhabdomyosarcoma (HN-RMS) treated by multidisciplinary therapy,and to analyze the prognostic factors,so as to guide the diagnosis and treatment.Methods Patients with HN-RMS admitted at Hematology Oncology Center of Beijing Children's Hospital (BCH),Capital Medical University between December 2012 and May 2017,were included in this case-observation study.The clinical characteristics were analyzed and the treatment effect and prognostic factors were summarized.Results A total of 48 cases were collected,including 36 boys and 12 girls,with a median age of 4.6 years.Primarysite parameningeal RMS(PM-RMS) (34 cases,70.8％),orbital (2 cases,4.2％) and non-orbital,non-parameningeal region(12 cases,25.0％) were found.Twenty cases belonged to alveolar type(41.7％),and 28 cases were of embryonaltype(58.3％).The diameter of the tumor was ＞5 cm(n =25,52.1％),and ≤5 cm(n =23,47.9％).IRS staging:there were 29 cases(60.4％) of stage Ⅱ-Ⅲ,19 cases (39.6％) of stage Ⅳ;29 cases (60.4％) of low-medium risk,and 19 cases (39.6％) of high risk.Twenty-three patients (47.9％) received surgery,and 25 cases (52.1％) received biopsy only.All patients (48 cases) received systemic chemotherapy.Twenty patients (41.6％) received external radiation,15 cases (31.3％) received 125I particle implantation,6 cases (12.5％) received proton therapy,but 3 cases (6.2％)did not receive radiation.The follow-up time lasted 13-57 months[(24.1 ± 12.3) months].The 2-year overall survival(OS) rate was (66.4 ± 7.2)％,and 2-year event free survival (EFS) rate was (59.9 ± 7.5) ％.Patients with tumor diameter ≤ 5 cm had higher OS and EFS than patients with tumor diameter ＞5 cm [2-year OS (87.4±6.8)％ vs.(42.9 ±6.8)％,2-year EFS (78.8 ±8.6％) vs.(38.5 ±10.8)％],and the differences were statistically significant (all P =0.006).Patients with orbital and non-orbital,non-parameningeal RMS had higher OS and EFS than PM-RMS [2-year OS 100％ vs.(87.5％ ± 11.7) ％ vs.(57.0 ± 8.8) ％;2-year EFS 100％ vs.(88.9 ± 10.5)％ vs.(51.1 ± 8.9)％],and the differences were statistically significant (P =0.008,P =0.030).Patients who received surgery had higher OS and EFS than those who did not received surgery [2-year OS (80.7±8.8)％ vs.(53.3 ± 10.4)％;2-year EFS (71.1 ±10.1)％ vs.(49.5±10.4)％],and the differences were statistically significant (P =0.008,P =0.026).COX regression analysis showed tumor diameter ＞ 5 cm was an adverse prognostic factor (OR =4.124,95％ CI:1.213-14.025,P =0.023).Conclusions PM-RMS accounted for a high proportion in RMS patients.The primary site and the size of the tumor are the main prognostic factors.Intensive therapy is expected to improve the prognosis of HN-RMS with meningeal invasion.

Objective To evaluate the effect of mild hypothermia combined with hydrogen-rich saline on cerebral injury after cardiac arrest and resuscitation in rats.Methods Healthy male Sprague-Dawley rats,aged 7-8 weeks,weighing 280-320 g,were divided into 5 groups (n=33 each) using a random number table method:sham operation group (group S),cardiac arrest and resuscitation group (group CAR),hydrogen-rich saline group (group H2),mild hypothermia group (group MH),and mild hypothermia plus hydrogen-rich saline group (group MH+H2).Cardiac arrest was induced with transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the cerebral injury model.Hydrogen-rich saline 5 ml/kg was intraperitoneally injected immediately after return of spontaneous circulation (ROSC) in H2 and MH+H2 groups,while the equal volume of normal saline was given instead in the other groups.The body temperature of rats was cooled down to 32-34℃ within 15 min starting from the time point immediately after ROSC and maintained for 4 h in MH and MH+H2 groups.Fifteen rats were selected at 24 h after ROSC to assess the neurological function score (NDS).Eighteen rats in each group were sacrificed at 24 h after ROSC,and brains were removed for microscopic examination of the pathological changes in hippocampal CA1 region after hematoxylin and eosin staining and for determination of pyramidal cell count and expression of glucose-regulated protein 78 (GRP78),C/EBP-homologous protein (CHOP),caspase-12,caspase-3,Bcl-2 and Bax in hippocampal CA1 region (by Western blot).Results Compared with group S,the NDS was significantly decreased,the pyramidal cell count was reduced,the expression of GRP78,CHOP,caspase-12,caspase-3 and Bax was up-regulated,and the expression of Bcl-2 was down-regulated in the other four groups (P＜0.05).Compared with group CA-R,the NDS and pyramidal cell count were significantly increased,the expression of GRP78 and Bcl-2 was up-regulated,and the expression of CHOP,caspase-12,caspase-3 and Bax was down-regulated in H2,MH and MH+H2 groups (P＜0.05).Compared with group H2 or group MH,the NDS and pyramidal cell count were significantly increased,the expression of caspase-3 and Bax was down-regulated,the expression of Bcl-2 was up-regulated (P＜0.05),and no significant change was found in the expression of GRP78,CHOP and caspase-12 in group MH+H2 (P＞ 0.05).Conclusion Combination of mild hypothermia and hydrogen-rich saline offers enhanced efficacy in reducing cerebral injury after cardiac arrest and resuscitation over mild hypothermia or hydrogen-rich saline alone in rats.