Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Objective To explore clinical outcomes and bone resection of interlaminar fenestration decompression and u-nilateral biportal endoscopic(UBE)technique in treating lumbar disc herniation(LDH).Methods A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021.Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3)years old,were treated with UBE,29 patients withL4.5and 25 patients with L5S1.There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of(39.9±10.0)years old,were treated with small fenestra-tion,25 patients with L4.5 and 26 patients with L5S1.Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups.Visual analogue scale(VAS)and Oswestry dis-ability index(ODI)were compared between two groups before operation and 1,3,6 and 12 months after operation,respective-ly;and modified MacNab evaluation criteria was used to evaluate clinical efficacy.Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups.Results All 105 patients were successfully completed operation.Both of two groups were followed up from 6 to 12 months with an average of(10.69±2.49)months.Oper-ation time,postoperative time of getting out of bed and hospital stay were(58.20±5.54)min,(2.40±0.57)dand(3.80±0.61)d in UBE group,and(62.90±7.14)min,(4.40±0.64)d and(4.40±0.64)d in small fenestrum group,respectively;and had sta-tistically difference between two groups(P＜0.05).Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery(P＜0.05).VAS of lumbar pain in UBE group(1.37±0.49)score was lower than that of small fenestration group(2.45±0.64)score,and had statistically difference(t=9.745,P＜0.05).Postoperative ODI in UBE group at 1 and 3 months were(28.54±3.31)％and(22.87±3.23)％,respectively,which were lower than those in small fenestra group(36.31±9.08)％and(29.90±8.36)％,and the difference was statistically significant(P＜0.05).There were no significant difference in VAS and ODI between two groups at other time points(P＞0.05).According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group.In small fenestration group,35 patients got excellent,12 good,and 4 fair.In UBE group,amount of bone resection on L4,5 segment was(0.45±0.08)cm3 and(0.31±0.08)cm3 on the segment of L5S1.In small fenestration group,amount of bone resection on L4.5 segment was(0.57±0.07)cm3 and(0.49±0.04)cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group(P＜0.05).In UBE group,retention rate of laminoid complex on L4,5 segment was(0.73±0.04)and L5S1 segment was(0.83±0.03),whileL4,5segment was(0.68± 0.06)and L5S1 segment was(0.74±0.04)in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P＜0.05).Conclusion Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher eficiency,faster postoperative recovery and less damage to bone structure.

Objective To explore the risk factors of early femoral head necrosis in patients with femoral neck fracture after operation,and to establish a nomogram prediction model.Methods A total of 167 patients with femoral neck fracture from Jan-uary 2020 to April 2022 were selected and divided into necrosis group and non-necrosis group according to whether femoral head necrosis occurred in the early postoperative period.There were 21 males and 17 females in the necrosis group,aged from 33 to 72 years old,with an average of(53.49±10.96)years old,and the time from injury to operation ranged from 40 to 67 hours,with average time of(53.46±7.23)hours.There were 72 males and 57 females in the non-necrosis group,aged from 18 to 83 years,with an average of(52.78±12.55)years old,and the time from injury to operation was 18 to 65 hours,with an aver-age time of(39.88±7.79)hours.The potential influencing factors,including patient gender,diabetes mellitus,hypertension,chronic liver disease,posterior inclination angle of the femoral head,operation mode,fracture displacement,fracture line loca-tion,preoperative braking traction,screw arrangement mode,reduction quality,age,body mass index(BMI),and injury to operation time were subjected to single factor analysis.Logistic multivariate regression analysis was conducted for factors with a significance level of P＜0.05.Results The incidence of femoral head necrosis in 167 patients with femoral neck fracture was 22.76％.The following factors were identified as independent risk factors for early postoperative femoral head necrosis in pa-tients with femoral neck fractures:coexisting diabetes[OR=5.139,95％CI(1.405,18.793),P=0.013],displaced fracture[OR=3.723,95％CI(1.105,12.541),P=0.034],preoperative immobilization[OR=3.444,95％CI(1.038,11.427),P=0.043],quality of reduction[OR=3.524,95％CI(1.676,7.411),P=0.001],and time from injury to surgery[OR=1.270,95％CI(1.154,1.399),P=0.000].The Hosmer-Lemeshow goodness-of-fit test(x2=3.951,P=0.862),the area under the receiver operator characteristic(ROC)curve was 0.944[P＜0.001,95％CI(0.903,0.987)],with a sensitivity of 89.50％,the specificity was 88.40％,the maxi-mum Youden index was 0.779,and the overall trend of the model correction curve was close to the ideal curve.Model regres-sion equation was Z=1.637 × diabetes+1.314× fracture displacement+1.237 × preoperative braking traction+1.260 × reduc-tion quality+0.239 ×injury to operation time-18.310.Conclusion The occurrence of early femoral head necrosis in patients with femoral neck fracture postoperatively is affected by multiple factors.The risk early warning model established according to the factors has good predictive efficacy.

Objective:To observe the effect and safety of the traditional Chinese medicine(TCM)Linggui Formula(LGF)in the treatment of asthenospermia with kidney deficiency and blood stasis.Methods:This randomized controlled trial included 90 ca-ses of asthenospermia with kidney deficiency and blood stasis treated in our hospital from September 2022 to September 2023,45 by oral medication with LGF(the trial group)and the other 45 with oral levocarnitine solution(the control group),all for 12 weeks.We followed up the patients for 12 weeks,recorded the semen parameters,TCM syndrome scores,sexual hormone levels,pregnancy rates,and DNA fragmentation index(DFI)of the patients,and compared them between the two groups before and after treatment.Re-sults:Totally,82 of the patients completed the study,42 in the trial and 40 in the control group.After treatment,the patients in the trial group showed significant increases in the percentage of progressively motile sperm(PMS)(from[19.25±3.08]% to[38.57±4.99]%,P<0.05),total sperm motility(from[32.29±3.64]% to[46.50±4.77]%,P<0.05)and sperm concentration(from[83.9±37.2]to[95.1±34.9]×106/ml],P<0.05),and so did the controls in PMS(from[19.75±4.28]% to[34.46±5.07]%,P<0.05),total sperm motility(from[33.02±4.93]% to[43.11±4.72]%,P<0.05)and sperm concen-tration(from[85.2±39.7]to[88.1±35.2]×106/ml,P<0.05),all even more significant in the trial than in the control group(P<0.05).No statistically significant difference was observed in the semen volume either in the trial(from[3.38±0.38]to[3.24±0.45]ml,P>0.05)or in the control group(from[3.46±0.52]to[3.30±0.37]ml,P>0.05),or between the trial and control groups(P>0.05),or in the sexual hormone levels,pregnancy rates,and sperm DFI between the two groups before and after treatment(P>0.05).Both groups of patients had good safety profiles without serious adverse reactions.Conclusion:Linggui Formula can improve the percentage of PMS in asthenospermia patients with kidney deficiency and blood stasis,potentially enhancing pregnancy rates and with a good safety.

The occurrence of male infertility is often related to the"kidney deficiency and kidney-essence chamber dysfunc-tion".This article proposes the application of the"kidney-essence chamber"theory in male infertility,outlines the origin of the theo-ry,and elucidates how the deficiency of essence,qi,yin and yang in the kidney affects fertility essence and leads to the dysfunction of the essence chamber manifested as the traditional Chinese medicine syndrome of mixed deficiency and excess.In clinical practice,fol-lowing the essence chamber-related principle of"keeping the six fu-organs unobstructed in function",targeting different types of syn-dromes and their pathogenesis,combined treatment of tonifying the kidney and dredging the essence chamber is conducive to the recov-ery of semen quality and improvement of male fertility.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.

Objective To investigate the effect and mechanism of transplantation of neuregulin1(NRG1)gene-modified bone marrow mesenchymal stem cells(BMSCs)on the repair of hemi-transected spinal cord injury(SCI)in rats.Methods Isolated and cultured rat BMSCs,followed by transfection with the NRG1 gene.The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method,and the proliferation activity of the BMSCs was detected by cell counting method.Forty-three healthy 8-week-old SD rats were randomly divided into control group(n=10),SCI model group(n=10),BMSCs group(n=10),and NRG1-BMSCs group(n=13).After establishing the spinal cord hemisection model,animals received in-situ transplantation of BMSCs or NRG1-BMSCs.On the 1,7,14,21,and 28 days after transplantation,the hind limb motor function was evaluated using BBB score and inclined plate test;on the 7th day after transplantation,the migration and distribution of transplanted cells was monitored using a fluorescence microscope;on the 28th day after transplantation,the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining;cell apoptosis using TUNEL staining,and levels of endoplasmic reticulum stress-related proteins[X-box binding protein 1(XBP1),C/EBP homologous protein(CHOP),activating transcription factor 4(ATF4),ATF6,glucose-regulated protein 78(GRP78)]and apoptosis-related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated protein X(Bax)]in rat spinal cord tissues using Western blotting.Results BMSCs were successfully isolated,cultured,and transfected with the NRG1 gene.ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner(P<0.05).The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs(P<0.05).On the 21 and 28 days after transplantation,the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group(P<0.05).However,it did not reverse to the level in control group(P<0.05).On the 28th day after transplantation,compared with the SCI model group and BMSCs group,neuronal pyknosis reduced,the Nissl body density increased,the expression levels of XBP1,CHOP,ATF4,ATF6,GRP78,and Bax,and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group(P<0.05),and the expression level of Bcl-2 significantly increased(P<0.05).Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats.The mechanism may be related to promoting the proliferation activity of BMSCs,inhibiting cell apoptosis,and mitigating endoplasmic reticulum stress.

Biliary tract cancer is a group of malignancies which originate from biliary epithelium, and adenocarcinoma is the main pathological type. Although surgical resection is the only radical treatment strategy, most biliary tract cancer patients are diagnosed at locally advanced stage or with distant metastasis. Biliary tract cancer is highly resistant to the conventional chemoradiotherapy and the emerging immunotherapy including immune checkpoint inhibitors, owing to the suppressive immune microenvironment. In a whole view, this paper discussed the anti-tumor and tumor-promoting immune responses of the various immune cells and stromal cells in the immune microenvironment of biliary tract cancer, as well as their correlation with prognosis. The understanding of the whole view of immune microenvironment in biliary tract cancer patients could further inform the design of clinical trials of immunotherapy or combination therapy.