OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group， model group， Runchang granules low-dose and high-dose groups （5， 10 g/kg）， mosapride group （0.003 g/kg， positive control）， with 6 mice in each group. The latter 4 groups were given loperamide intragastrically （0.004 g/kg）， twice a day， for 3 consecutive days. Normal control group and model group were given purified water intragastrically， and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication， fecal moisture content and intestinal motility of mice were determined， while the structures of colon and ileum， and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor （c-kit）， mucin 2 （MUC2） and stem cell factor （SCF） were determined in colon； meanwhile， the mRNA expression levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， inducible nitric oxide synthase （iNOS）] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase （nNOS）， smooth muscle myosin light chain kinase （smMLCK）， 5-hydroxytryptamine 4 receptor （5-HT4R）， MUC2， SCF， c-kit] were determined. RESULTS Compared with model group， the fecal water content， intestinal propulsion rate， protein expression of c-kit in colon， relative expressions of MUC2 and SCF protein， and mRNA expressions of factors related to promoting intestinal motility （except for nNOS and SCF in Runchang granules low-dose group） were all increased significantly in Runchang granules low-dose and high-dose groups， and mosapride group （P＜0.05 or P＜0.01）. mRNA expression levels of inflammatory factors were decreased significantly（P＜0.05 or P＜0.01）. Both colon and ileum injuries improved， and the secretion of colon mucus was increased significantly in Runchang granules high-dose group （P＜0.01）. CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice， and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression， and the activation of SCF/c-kit signaling pathway.

Objective To analyze the prevalence and genetic characteristics of influenza A(H3N2) viruses in the city of Xiangyang in 2022-2023, and to provide a scientific basis for predicting the epidemic and mutation of influenza virus. Methods Throat swab specimens of the influenza like cases were collected from national influenza monitoring sentinel hospitals in Xiangyang every week. RNA was extracted from the specimens for influenza diagnosing using real-time RT-PCR．Viruses were isolated from H3N2 positive specimens, and HA and NA genes were amplified and sequenced．3D modeling analyses were conducted. Results The gene phylogenetic tree showed that the H3N2 isolates in 2022-2023 belonged to 3C.2a1b.2a1 and 3C.2a1b.2a2 branches, respectively. The A(H3N2) influenza virus strains all had amino acid point mutation sites on important antigenic determinants of HA protein. The epitope mutations of the 2022 A(H3N2) strain mainly occurred in regions B, C, and D. The epitope mutations of the A(H3N2) strain in 2023 mainly occurred in regions C and D. Different glycosylation sites of HA gene were found in 2022-2023 strains. No variation was found in key amino acid sites associated with neuraminidase inhibitor resistance. The difference of overall structure was not obvious in the three-dimensional simulation structure diagram. Conclusion The A(H3N2) influenza strains isolated in this study have shown antigenic drift, especially the mutation of HA, which may affect the protective effect of the vaccine on the local population and lead to influenza epidemic. The variations of HA and NA suggest that close attention should be paid to the epidemic and genetic variation of H3N2 subtype influenza virus, to provide a scientific basis for the selection of influenza virus vaccine strains and the prevention and control of influenza.

Objective To investigate the effect of orthokeratology(OK)lens decentration on peripheral retinal defo-cus in myopic eyes.Methods Totally 154 patients(234 eyes)continuously wearing OK lenses for one month or more were recruited in this study.According to the location of defocus rings in corneal topography,these eyes were divided into the centration group(118 eyes)and the decentration group(116 eyes).Peripheral retinal defocus data of each patient was collected by multispectral refraction topography,including total refraction difference value(TRDV),refraction difference value at 15°(RDV-15),refraction difference value at 30°(RDV-30),refraction difference value at 45°(RDV-45),superior refraction difference value(RDV-S),inferior refraction difference value(RDV-I),temporal refraction difference value(RDV-T)and nasal refraction difference value(RDV-N).An independent sample t-test was used to compare the differ-ences in these parameters between the two groups,and multivariate correlation analysis(generalized estimating equation,GEE)was conducted to analyze the relationship between clinical parameters and the amount of peripheral retinal defocus within the group.Results The RDV-N of patients in the decentration group was significantly lower than that in the cen-tration group(t=2.668,P=0.008),and there were no significant differences in other parameters(all P＞0.05).GEE showed that age was the determinant of RDV-S,and they were positively correlated;steep K was the determinant of RDV-I,and they were negatively correlated;gender was the determinant of RDV-T,and female OK lens wearers showed less RDV-T;the determinants of RDV-N include the alignment of OK lens,eye distribution and age,among which,RDV-N was positively corrected with age,and RDV-N of the left eyes was significantly superior to that of the right eyes.Conclusion Subclinical decentration of the OK lens may result in better RDV-N of myopia patients.The peripheral retinal defocus is influenced by factors such as age,gender,steep K,amount of decentration and eye distribution of OK lens wearers.

Objective To evaluate the survival of patients with diffuse large B-cell lymphoma(DLBCL)after chemotherapy using Fuzheng Jiedu Formula and to explore the intrinsic correlation between the lymphocyte subset level and the survival of patients with DLBCL.Methods A total of 234 patients with DLBCL who had completed chemotherapy and achieved complete or partial response in the Department of Hematology,Longhua Hospital Shanghai University of Traditional Chinese Medicine and Shanghai East Hospital,Tongji University from January 1,2013,to December 31,2023,were recruited.A cohort study design was adopted,with"whether to receive continuous Fuzheng Jiedu Formula treatment for≥6 months after chemotherapy"as the exposed factor.Patients meeting this exposed factor were divided into the traditional Chinese medicine(TCM)cohort,whereas those who did not meet this exposed factor were divided into the observation cohort.The 1-and 2-year progression-free survival(PFS)rate,overall survival(OS)rate,and duration of response(DOR)of the two cohorts were compared.The survival curves of PFS and OS of the two cohorts were drawn,and subgroup survival analysis was performed to determine factors affecting disease progression.The effect of Fuzheng Jiedu Formula on lymphocyte subset count level was observed.Results The study included 126 and 108 patients in the TCM and observation cohorts,respectively.Compared with the observation cohort,the 2-year PFS rate,2-year OS rate,and DOR were increased in the TCM cohort(P<0.05).The PFS in the TCM cohort was higher than that in the observation cohort[HR=0.542,95%CI(0.345-0.853),P<0.01].The result of subgroup analysis showed that PFS in the TCM cohort was higher than that in the observation cohort in the age≥60 years,AA stage Ⅲ-Ⅳ,CD4+

Objective To investigate the effects of remifentanil and dexmedetomidine controlled hypotension on coagulation function,cerebral oxygen metabolism and amino acid neurotransmitter levels in elderly patients undergoing orthopedic surgery.Methods The elderly patients who underwent lower extremity orthopedic surgery were divided into group A(given dexmedetomidine for hypotension),group B(given remifentanil for hypotension)and group C(given remifentanil combined with dexmedetomidine for hypotension)according to different anesthetic drugs.Systolic blood pressure(SBP),diastolic blood pressure(DBP)and heart rate(HR)were compared among the 3 groups.Cerebral oxygen metabolism[arterial oxygen content,(CaO2),oxygen saturation of internal jugular vein(SjvO2),oxygen content of internal jugular vein(CjvO2)],coagulation function[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),plasma fibrinogen(FIB)],amino acid neurotransmitters[glutamic acid(Glu),aspartate(Asp),gamma-aminobutyric acid(GABA)]were compared,and the occurrence of adverse drug reactions during the trial were compared.Results At 12 h after anesthesia,the APTT of group A,group B and group C were(17.26±2.77),(17.37±2.92)and(31.11±4.74)s,respectively.GABA were(18.74±2.71),(19.22±2.60)and(23.37±2.59)mmol·L-1,respectively.3 min after withdrawal,CaO2 in group A,group B and group C were(139.31±9.03),(140.90±8.70)and(131.75±10.11)mL·L-1,respectively;SjvO2 were(63.59±2.23)％,(63.40±2.44)％and(68.82±3.36)％,respectively.The above indexes of group C were compared with those of group A and group B,and the differences were statistically significant(all P＜0.05).The incidence of adverse drug reactions in group A,B and C were 12.82％,27.50％and 7.32％,respectively.The incidence of adverse drug reactions in group C were lower than that in group A and group B(P＜0.05).Conclusion Remifentanil combined with dexmedetomidine for controlled hypotension in elderly orthopedic surgery has better blood pressure control effect,can improve postoperative coagulation function,maintain cerebral oxygen metabolism balance,reduce cognitive function injury and anesthesia adverse drug reactions.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective:To analyze the clinical efficacy of arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip.Methods:A total of 30 patients (12 males and 18 females) with bilateral external snapping hip underwent arthroscopic transverse release of the iliotibial band through peritrochanteric space in Department of Sports Medicine, Senior Department of Orthopaedics, the Fourth Medical Center, Chinese PLA General Hospital were retrospectively analyzed from May 2021 and June 2022. The average age was 32.5±8.2 years (range, 17-51 years). At the same time, 30 patients who underwent arthroscopic external release of the iliotibial band through the external surface of the iliotibial band (external iliotibial band group) were selected as control group, including 13 males and 17 females, aged 29.5±6.8 years (range, 11-45 years). The visual analogue scale (VAS), modified Harris hip score (mHHS), and gluteal muscle contracture disability scale (GDS) were compared between the two groups at preoperative, 6 months postoperative, and final follow-up.Results:All patients successfully completed the operation and were followed up for 17.5±3.3 months (range, 12-25 months). The VAS scores of the two groups at the last follow-up were lower than those before operation ( P<0.05). The mHHS scores before operation, 6 months after operation and at the last follow-up in the peritrochanteric space group were 76.5 (67.0, 85.5), 98.5 (94.8, 100.0) and 100.0 (97.0, 100.0), respectively, and those in the external iliotibial band group were 80.5 (70.0, 86.0), 100.0 (96.0, 100.0) and 100.0 (99.5, 100.0). The differences in mHHS scores between the two groups were statistically significant for intragroup comparisons ( P<0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in mHHS scores between groups at different time points ( P>0.05). The GDS before operation, at 6 months after operation and at the last follow-up were 47.0 (35.8, 64.5), 90.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the peritrochanteric space group, and 51.0 (38.0, 64.5), 50.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the external iliotibial band group, respectively. The differences in GDS between the two groups were statistically significant for intragroup comparisons ( P< 0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in GDS between groups at different time points ( P>0.05). Conclusion:Arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip can effectively reduce hip pain and improve hip function, with satisfactory clinical results, and can be used as an alternative treatment to transverse release through the external surface of the iliotibial band.