[Objective]To do textual research on the meaning of"Fanteng"(烦疼)and"Tengfan"(疼烦)in Treatise on Febrile Diseases and Synopsis of the Golden Chamber.[Methods]By reviewing the annotations and commentaries from different scholars throughout history,the paper summarizes and analyzes their different viewpoints.Additionally,through philological research and references to medical and non-medical literature from the Qin and Han Dynasties,the paper seeks to ascertain the semantic meaning of the word"Fan"(烦).Furthermore,by analyzing ZHANG Zhongjing's original text,the paper explores the intended meanings of these two symptoms.[Results]Scholars throughout history have interpreted these two symptoms as intense pain,pain accompanied by restlessness and inappropriate pain caused by heat.In addition to expressing the uncomfortable feeling of mind,"fan"(烦)also means numerous and frequent.In ZHANG Zhongjing's original texts,these two symptoms are used in conjunction with specific body parts,in dampness disease,malaria and Shaoyang disease,etc.,indicating frequent and recurring pain.[Conclusion]In ZHANG Zhongjing's original texts,"Fanteng"(烦疼)and"Tengfan"(疼烦)actually refer to the concept of"frequent pain".

Objective:To compare the effects of citrate and heparin anticoagulation on coagulation function and efficacy in children with septic shock undergoing continuous blood purification (CBP), and to provide guidance for CBP anticoagulation in children with septic shock.Methods:A case control study was conducted. Thirty-seven children with septic shock admitted to the pediatric intensive care unit (PICU) of the First Affiliated Hospital of Gannan Medical University from July 2019 to September 2022 were enrolled as the research subjects. The patients were divided into citrate local anticoagulation group and heparin systemic anticoagulation group according to different anticoagulation methods. The baseline data, the level of coagulation indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), D-dimer] before treatment and 1 day after weaning from CBP, serum inflammatory mediators [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitivity C-reactive protein (hs-CRP), procalcitonin (PCT)], bleeding complications during CBP and 7-day mortality were collected.Results:A total of 37 cases were enrolled finally, including 17 cases with citric acid local anticoagulation and 20 cases with heparin systemic anticoagulation. There was no statistically significant difference in general data such as gender, age, and body weight of children between the two groups. There were no statistically significant differences in baseline levels of coagulation indicators and inflammatory mediators before treatment of children between the two groups. One day after weaning from CBP, both groups showed varying degrees of improvement in coagulation indicators compared with those before treatment. Compared with before treatment, the PT of the heparin systemic anticoagulation group was significantly shortened after 1 day of weaning (s: 11.82±2.05 vs. 13.64±2.54), APTT and TT were significantly prolonged [APTT (s): 51.54±12.69 vs. 35.53±10.79, TT (s): 21.95±4.74 vs. 19.30±3.33], D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 4.94±3.94), with statistically significant differences (all P < 0.05). While in the citrate local anticoagulation group, only APTT was significantly prolonged after treatment compared with that before treatment (s: 49.28±10.32 vs. 34.34±10.32, P < 0.05). There were no statistically significant differences in other coagulation indicators compared with before treatment. Compared with the citric acid local anticoagulation group, the PT of the heparin systemic anticoagulation group was significantly shortened after treatment (s: 11.82±2.05 vs. 13.61±3.05, P < 0.05), and the D-dimer level was significantly reduced (mg/L: 1.92±1.58 vs. 3.77±2.38, P < 0.01). The levels of inflammatory mediators in both groups were significantly reduced 1 day after CBP weaning compared with those before treatment [citric acid local anticoagulation group: hs-CRP (mg/L) was 12.53±5.44 vs. 22.65±7.27, PCT (μg/L) was 1.86±1.20 vs. 3.30±2.34, IL-6 (ng/L) was 148.48±34.83 vs. 202.32±48.62, TNF-α (ng/L) was 21.38±7.71 vs. 55.14±15.07; heparin systemic anticoagulation group: hs-CRP (mg/L) was 11.82±4.93 vs. 21.62±8.35, PCT (μg/L) was 1.90±1.08 vs. 3.18±1.97, IL-6 (ng/L) was 143.81±33.41 vs. 194.02±46.89, TNF-α (ng/L) was 22.44±8.17 vs. 56.17±16.92, all P < 0.05]. However, there was no statistically significant difference between the two groups (all P > 0.05). There was no statistically significant difference in bleeding complication during CBP and 7-day mortality in children between the citrate local anticoagulation group and the heparin systemic anticoagulation group (5.9% vs. 30.0%, 17.6% vs. 20.0%, both P > 0.05). Conclusions:Heparin for systemic anticoagulation and regional citrate anticoagulation can significantly reduce the levels of IL-6, TNF-α, hs-CRP and PCT in children with septic shock, and relieve inflammatory storm. Compared with citric acid local anticoagulation, heparin systemic anticoagulation can shorten the PT and reduce the level of D-dimer in children with septic shock, which may benefit in the prevention and treatment of disseminated intravascular coagulation (DIC).

ObjectiveThe functional model of six major components of Astragali Radix-Angelicae Sinensis Radix combination against the proliferation of vascular smooth muscle cells （VSMCs） was constructed by uniform design， the relationship between the compatibility of these six main components and the inhibition of VSMCs proliferation was analyzed， and the effect of the compatibility of these main components of Astragali Radix-Angelicae Sinensis Radix on the proliferation of VSMCs as well as the feasibility of uniform design test in the study of multi-component compatibility of Chinese medicines were discussed. MethodCell proliferation and toxicity assay kit （CCK-8） method was used to determine the inhibitory effect of the six components of Astragali Radix-Angelicae Sinensis Radix on platelet derived growth factor-BB （PDGF-BB）-induced VSMCs proliferation in rats and the half inhibitory concentration （IC₅₀） of each component were obtained. Six chemical components of Astragali Radix-Angelicae Sinensis Radix （formononetin， astragaloside Ⅰ， astragaloside Ⅳ， calycosin， ferulic acid and calycosin-7-O-β-D-glucoside） were taken as the independent variables X₁， X₂， X₃， X₄， X₅， X₆， respectively， and the cell proliferation inhibition rate as the dependent variable Y. U24*（24⁹） uniform design table and mathematical models （including linear and quadratic polynomial） were selected， the stepwise regression method was used to screen the variables， and the better equations were obtained in theory. The actually better relationship equations were screened by setting the different dose compatibility of these six components for verification tests. According to the purpose of the experiment， the selected regression equation was processed by data centralization， so as to compare the regression coefficients of the data centralization equation and analyze the correlation between components and efficacy. ResultThe six components of Astragali Radix-Angelicae Sinensis Radix could inhibit abnormal proliferation of VSMCs in a dose-dependent manner. IC₅₀ values of formononetin， astragaloside Ⅰ， astragaloside Ⅳ， calycosin， ferulic acid and calycosin-7-O-β-D-glucoside were 123.453， 113.184， 81.655， 141.159， 101.187， 151.016 mg·L^-1， respectively. Two superior models were selected by experimental verification， including equation 1 of Y₁=73.137 897-0.207 888X₁+0.000 508X₂²+0.000 347X₁X₆ and equation 2 of Y₂=70.038 433-0.236 665X₁+0.000 577X₂²+0.000 260X₁X₄+0.000 415X₁X₆+0.000 370X₃X₅. After data centralization， equation 2 was adjusted to Y=-1.480 260-0.146 281X₁+0.000 673X₂²+0.000 314X₁X₄+0.000 456X₁X₆+0.000 737X₃X₅， the regression coefficients showed that the astragaloside Ⅰ had a positive effect on the inhibition rate of cell proliferation， formononetin-calycosin， formononetin-calycosin-7-O-β-D-glucoside and astragaloside Ⅳ-ferulic acid had an interaction effect on the inhibition rate of cell proliferation， and the synergistic effect of astragaloside Ⅳ and ferulic acid was higher than other interaction items. ConclusionThe combination of six main components of Astragali Radix-Angelicae Sinensis Radix can inhibit the abnormal proliferation of VSMCs， and it is demonstrated that the uniform test design can be used to predict the correlation between the chemical composition of Chinese medicines with their pharmacological effects， which can provide an experimental basis for the rational use of uniform design and regression analysis to construct mathematical models to study the compatibility relationship of Chinese medicines.

Objective:To investigate the expression of coronavirus disease 2019 (COVID-19) transmission-related receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human conjunctival tissue and its clinical significance.Methods:Fifty human conjunctival tissue specimens from 50 patients including 10 normal conjunctival tissues, 15 conjunctival papilloma tissues, 15 conjunctival nevus tissues and 10 conjunctival cyst tissues were collected from June 2019 to June 2020 at Xi'an People's Hospital.Ten corneal tissue samples from 10 patients with eyes removed due to trauma were collected as control.The distribution of ACE2 and TMPRSS2 in different corneal tissues was detected by the immunohistochemistry.The expression of ACE2 and TMPRSS2 was scored and compared.Reuse of the human samples and the research protocol was approved by an Ethics Committee of Xi'an People's Hospital (No.20190022). Written informed consent was obtained from each patient.Results:ACE2 and TMPRSS2 were both expressed in normal conjunctival epithelium, epithelial cells in conjunctiva papilloma and conjunctival nevus, and cells in conjunctiva cyst wall.ACE2 was mainly distributed in the superficial and intermediate cells of conjunctival epithelium, but not in the basal cells and goblet cells.TMPRSS2 was found in different layers of cells.The positive expression rates of ACE2 and TMPRSS2 in conjunctiva were both 100%.There was no significant difference in the expression intensity of ACE2 and TMPRSS2 among normal conjunctival tissue, conjunctival papilloma, conjunctival nevus and conjunctival cyst (all at P>0.05). Weakly expressed in corneal tissues, ACE2 and TMPRSS2 were more moderately and strongly expressed in conjunctival tissues.There were significant differences in the number of differently graded ACE2 and TMPRSS2 expression between normal conjunctival tissues, conjunctival papilloma, conjunctival nevus, conjunctival cyst and corneal tissues (ACE2: Z=-3.473, -4.183, -3.970, -3.873, all at P<0.01; TMPRSS2: Z=-4.119, -4.472, -4.443, -4.147, all at P<0.001). Conclusions:COVID-19 transmission-related receptors ACE2 and TMPRSS2 are expressed in human conjunctival tissue, which provides organological evidence for ocular surface transmission of COVID-19.

Objective:To compare the clinical characteristics of critically ill pregnant women admitted to the intensive care unit (ICU) with different admission methods, in order to make more effective and rational use of ICU resources.Methods:A retrospective study was conducted. The clinical data of critically ill pregnant women admitted to ICU of Peking University Third Hospital from January 2006 to July 2019 were analyzed. According to the admission mode to ICU, the pregnant women were divided into emergency admission group (transferred to ICU on the same day or the next day due to critical illness) and planned admission group (transferred to ICU 2 days after admitting in obstetric ward). The clinical characteristics of ICU critical pregnant women, such as the incidence, causes of admission, severity of the disease, main treatment measures, mortality, and medical expenses were collected, and a comparative analysis between the two groups was performed.Results:During the nearly 14 years, a total of 576 critical pregnant women in ICU were enrolled, accounting for 0.8% (576/71 790) of the total number of obstetric inpatients and 4.6% (576/12 412) of the total number of ICU inpatients. Seven maternal deaths accounted for 1.2% of all critically pregnant women transferred to ICU, and the overall mortality of pregnant women was 10/100 thousand. Of the 576 critically pregnant women, there were 327 patients (56.8%) in the emergency admission group and 249 patients (43.2%) in the planned admission group. Compared with the planned admission group, the proportion of elective cesarean section in the emergency admission group was significantly lower (17.7% vs. 94.0%, P < 0.01), and the proportion of emergency cesarean section was significantly higher (65.1% vs. 2.4%, P < 0.01), the acute physiology and chronic health evaluation (APACHE Ⅱ, APACHE Ⅲ) scores, simplified acute physiology score Ⅱ (SAPS Ⅱ) and Marshall score were significantly higher [APACHE Ⅱ score: 6.0 (4.0, 9.8) vs. 4.0 (3.0, 7.0), APACHE Ⅲ score: 14.0 (11.0, 20.3) vs. 12.0 (9.0, 16.0), SAPS Ⅱ score: 8 (0, 12) vs. 3 (0, 8), Marshall score: 2 (1, 4) vs. 1 (1, 3), all P < 0.01]. The length of ICU stay in the emergency admission group was significantly longer than that in the planned admission group [days: 2 (1, 5) vs. 2 (1, 3), P < 0.01], and the total length of hospital stay was significantly shorter [days: 9 (7, 13) vs. 13 (10, 18), P < 0.01]. Both in the emergency admission group and the planned admission group, obstetric factors were the main reason for admission, 60.9% (199/327) and 70.3% (175/249), respectively. The proportion of postpartum hemorrhage was the highest [35.2% (115/327) and 57.0% (142/249)], followed by preeclampsia/eclampsia [7.0% (23/327) and 7.6% (19/249)]. Only 7 of the 19 critically pregnant women with puerperal infection were planned admission. All 21 patients with acute fatty liver of pregnancy (AFLP) during pregnancy were emergency admission. Among the emergency and planned admission patients, 73 patients (22.3%) and 42 patients (16.9%) required mechanical ventilation (duration of mechanical ventilation > 24 hours), 99 patients (30.3%) and 35 patients (14.1%) needed vasoactive agents, 67 patients (20.5%) and 20 patients (8.0%) received hemodynamic monitoring, and 123 patients (37.6%) and 154 patients (61.8%) were given anticoagulation therapy, respectively. In terms of severity score of critical pregnant women, there were significant differences in APACHE Ⅱ, APACHE Ⅲ, SAPS Ⅱ and Marshall scores of pregnant women with different diseases. Among them, the APACHE Ⅲ, SAPS Ⅱ and Marshall scores of AFLP were the highest [21.0 (15.0, 32.5), 12.0 (6.0, 16.5) and 6.0 (3.5, 8.0), respectively]. The APACHE Ⅱ and APACHE Ⅲ scores of postpartum hemorrhage were the lowest [4.0 (3.0, 7.0), 12.0 (10.0, 16.0)]. The SAPS Ⅱ score of pneumonia was the lowest [2.0 (0, 14.0)]. The Marshall score for puerperal infection was the lowest [1.0 (0, 3.0)]. In terms of the total medical expenses, the cost in the emergency admission group was significantly lower than that in the planned admission group [10 thousand Yuan: 3.1 (2.0, 4.7) vs. 4.1 (2.9, 5.8), P < 0.05]. Conclusions:Compared with the critically ill pregnant women who planned to be admitted to ICU, the patients emergency admitted to ICU were more complicated and urgent, and the severity of the condition was scored higher. At present, the severity scoring system commonly used in ICU can only partly evaluate the severity of critically ill pregnant women, therefore, it is necessary to design the specific severity scoring system for critically ill pregnant women to effectively and rationally use the precious ICU resources.

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis

Objective: To understand the mechanism of chemotherapy resistance in nasopharyngeal carcinoma under hypoxic conditions through the perspective of protein SUMOylation modification. Methods: Cobalt chloride (CoCl₂) was used to establish the hypoxic model of human nasopharyngeal carcinoma CNE1 cells. Then, the cell cycle was detected by flow cytometry, and the expression level of small ubiquitin-related modifier(SUMO) and cyclin-dependent kinase 6 (CDK6) proteins were detected by western blotting. MTT assay was used to determine the median lethal dose (IC₅₀) of cancer cells against cisplatin, and enzyme-linked immunosorbent assay (ELISA) was used to determine lactate dehydrogenase (LDH) level. Results: The cell cycle of CNE1 induced by hypoxia was arrested in G0/G1 phase.The results of Western blot showed that the protein expression level of CDK6 in CNE1 cells was lower than that in the control group (0.83±0.25 vs. 0.43±0.21, t=14.67, P=0.003). The protein level of conjugated SUMO1 was significantly lower than that in the control group (2.69±0.48 vs. 1.38±0.31, t=17.22, P=0.001), while the level of free SUMO1 protein was significantly higher than that in the control group (2.01±0.43 vs. 2.60±0.59, t=15.45, P=0.002).The LC50 of CNE1 cells in the control group was significantly lower than that in the hypoxic group (29.44 μg/ml vs. 97.72 μg/ml, t=12.79, P=0.001). After CNE1 cells received 50 μg/ml cisplatin for 48 h, the LDH content in the supernatant of the control group was significantly higher than that in the hypoxic group ((541.49±64.59) ng/ml vs. (234.67±41.03) ng/ml, t=11.94, P=0.007)). The apoptosis rate of CNE1 cells in the control group was significantly higher than that in the hypoxic group ((76.64±5.37)% vs. (32.84±4.77) ng/ml, t=8.49, P=0.003)). Conclusion Hypoxia can dissociate the covalent modification of CDK6 and SUMO1, inhibit cell cycle and increase the chemotherapy resistance of nasopharyngeal carcinoma.

Objective To investigate the levels of T helper cell 17 (Th17), Th17-related cytokines in-terleukin 17 (IL-17) and interleukin 23 (IL-23) and regulatory T cell (Treg) in relapsing remitting multiple sclerosis (RRMS). Methods In a case-control study, plasma was collected from RRMS patients (n=20) and healthy subjects as control group (n=20). The percentages of Th17 and Treg cells and the levels of IL-17 and IL-23 were tested. The levels of Th17, Treg, IL-17 and IL-23 of the two groups were compared. Patients were treated with methylprednisolone. The levels of Th17, Treg, IL-17 and IL-23 of multiple sclerosis (MS) patients b efore and after treatment were compared. Expanded disability status scale (EDSS) score and the number of Gd-enhancing lesions were evaluated in the case group. Statistical analysis was made by body mass index (IBM) statistical program for social sciences (SPSS) 17.0 software. Independent sample t test was conducted to compare the measurement data of the case group and the healthy control group, and enumeration data were compared by χ2 test; paired sample t test was performed to compare the data of the case group before and after treatment; Pearson correlation analysis was made forthe variables of the MS group before treatment. Results In the RRMS group, the percentage of Th17 cells in peripheral blood was significantly higher than the control group [(2.10±0.45)％vs (1.09±0.20)％](t=9.130, P<0.01), the levels of Th17-related cytokines IL-17 and IL-23 were remarkably higher than the control group (IL-17:t=19.843, P<0.01;IL-23:t=22.747, P<0.01), and the percentage of Treg cells was significantly lower than the control group [(1.33 ±0.30)％vs (2.52±0.30)％], (t=12.422, P<0.01). The levels of Th17 and IL-17 were positively associated with EDSS score (Th17: r=0.458, P<0.05; IL-17: r=0.480, P<0.05), there was no significant-correlation between the level of IL-23 and EDSS score (r=0.368, P>0.05), and Th17, IL-17 and IL-23 were positively correlated with the number of Gd-enhancing lesions (Th17: r=0.446, P<0.05; IL-17: r=0.544, P<0.05; IL-23: r=0.461, P<0.05). The levels of Th17, IL-17 and IL-23 in the RRMS group after the treatment with methylprednisolone were obviously decreased than before treatment (Th17: t=5.747, P<0.01; IL-17: t=9.967, P<0.01; IL-23: t=14.697, P<0.01), while that of Treg was apparently increased (t=10.050, P<0.01). Compared with the control group, the levels of Th17, IL-17 and IL-23 in the RRMS group after treatment were higher (Th17: t=6.889, P<0.01;IL-17:t=7.185, P<0.01;IL-23:t=13.284, P<0.01), and the percentage of Treg was lower (t=7.622, P<0.01). EDSS score of the RRMS group after treatment was remarkably decreased than before treatment(t=6.190, P<0.01), but the number of Gd-enhanced lesions after treatment was no significantiy changed (t=1.453, P>0.05). Conclusion Th17/Treg expression imbalance and Th17-related cytokines IL-17, IL-23 may participate in the pathological process of MS, and they might be therapeutic target for MS.

Objective: To analyse the clinicopathologic features of gastric plexiform fibromyxoma (PF) including diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Eight cases of PF were collected from June 2006 to June 2017 at the Second Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University. The clinicopathologic findings of eight cases of PF were retrospectively analyzed, and immunohistochemistry (EnVision method) and molecular detection of glioma-associated oncogene homologue 1 (GLI1) gene translocation were performed. All cases were histologically reviewed with immunohistochemical staining for smooth muscle actin (SMA), CD10, CD117, DOG1, CD34, ER, PR, ALK and S-100. Fluorescence in situ hybridization (FISH) was used to detect the GLI1 gene translocation, and mutation of CKIT exons 9, 11, 13 and 17; and PDGFRA exons 12, 14 and 18 were identified by Sanger sequencing in four cases. Relevant literature was reviewed. Results: The study included four men and four women, age ranged from 26 to 72 years (mean 51 years). Histologically, the tumors were rich in small thin-walled blood vessels and myxoid matrix, and exhibited multiple nodular growth pattern in the gastric wall. The tumor cells were bland, spindled or oval. Immunohistochemically, all cases strongly expressed vimentin and SMA, and some expressed CD10 (4/8), desmin (3/8), H-caldesmon (5/8) and PR (5/8), but were negative for CD34, S-100, ER, ALK, CD117 and DOG1. The GLI1 gene translocation detection was performed in eight cases by FISH with three positive cases and five negative cases. Mutation analyses for exons 9, 11, 13, and 17 of CKIT genes and exons 12, 14, and 18 of the PDGFRA genes were performed and the tumors all of four tested cases were wild-type. Seven patients were followed up (ranged from 24 to 95 months, mean 50 months) after diagnosis and none of the patients had recurrence or metastasis. Conclusions PF is a rare novel mesenchymal tumor of the stomach. Its distinct clinicopathologic features and immunohistochemical positivity for SMA, CD10 and PR can help differentiating this entity from other gastrointestinal mesenchymal tumors. FISH detection of GLI1 gene translocation offers an additional molecular diagnostic marker for the diagnosis.

Objective: To study clinical and pathologic characteristics of leiomyomas of the gastrointestinal tract, and to investigate the distribution characteristics of interstitial cells of Cajal ( ICCs ) in gastrointestinal leiomyomas. Methods: One hundred and forty-seven cases of leiomyomas of gastrointestinal tract were collected at the Second Affiliated Hospital of Zhengzhou University from June 2012 to June 2017. Clinical and pathologic findings were analyzed, combined with immunohistochemistry, Alcian blue-osafranin staining and molecular study. Results: The age of patients ranged from 13-82 years with mean age of 52 years. Male to female ratio was about 1∶2. Histologically, all tumors were composed of ovoid to spindle cells arranged in short intersecting fascicles. All tumors were diffusely and strongly positive for smooth muscle antibodies, desmin and h-caldesmon by immunohistochemical staining. A prominent interspersed subpopulation of elongated/dendritic-like cells with CD117 and DOG1 positivity (accounting for 1% to 30% of all tumor cells) and negative for Alcian blue-osafranin staining was identified in all esophageal leiomyomas, 16 of 20 (80%) gastric leiomyomas and 3 of 12 small bowel leiomyomas, but none in colonic/rectal leiomyomas. Mutational analysis in 16 cases showed absence of mutation in exons 9, 11, 13 or 17 of C-KIT and exons 12 or 18 of PDGFRA. Conclusions ICCs are identified in esophageal and gastric leiomyomas, as well as in small percentage of intestinal leiomyomas. Such findings may bring significant diagnostic pitfalls for misdiagnosis as gastrointestinal stromal tumor. Careful attention to the distribution of CD117 and DOG1 positive cells and molecular mutation analysis of C-KIT and PDGFRA may be necessary to establish the correct diagnosis.