Objective:To compare the characteristics of corneal stromal demarcation line after different surgical methods of riboflavin/ultraviolet A corneal collagen cross-linking (CXL) in early keratoconus, and analyze the influence of the demarcation line on the cross-linking effect.Methods:A non-randomized controlled clinical study was conducted.Sixty-nine eyes of 69 patients treated with riboflavin/ultraviolet A CXL in the Eye Hospital of Shandong First Medical University from May 2019 to February 2021 were included.According to the cross-linking methods, the patients were divided into epithelium-on treatment group (21 eyes) and epithelium-off treatment group (48 eyes). There were 25 eyes in 5.4 J energy group and 44 eyes in 7.2 J energy group.The morphology and changes of corneal stromal cross-linking reaction (corneal stromal demarcation line) were observed at 2 weeks, 1, 3 and 4 months after operation.Changes in the thinnest corneal thickness (TCT), uncorrected visual acuity (UCVA, LogMAR), best corrected visual acuity (BCVA, LogMAR) and corneal maximum curvature (Kmax) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.2019.05). Written informed consent was obtained from each subject.Results:Of the 69 eyes after operation, 44 eyes (63.77%) had demarcation lines, and 25 eyes (36.23%) had no demarcation lines.The occurrence rate of demarcation lines in the epithelium-on treatment group was 79.17%(38/48), which was significantly higher than 28.57%(6/21) in the epithelium-off treatment group ( χ2=16.186, P<0.01). The occurrence rate of demarcation line in 5.4 J energy group was 72.00%(18/25), and the 7.2 J energy group was 56.80%(25/44), with no significant difference ( χ2=1.565, P=0.302). Slit lamp microscopy and anterior segment-optical coherence tomography showed that the demarcation line appeared at 1-2 weeks after operation, gradually converged and strengthened after 1 month, turned diffuse, blurred and faded by degrees after 2-3 months, and basically disappeared after 4 months.The depth of the demarcation line reached 141-423 μm, with an average depth of (263.44±84.22)μm.Scanning laser confocal microscopy showed that corneal stromal cells were activated and light reflection was enhanced after CXL.Collagen fibers extended vertically and horizontally, crisscrossed, and were in a reticular arrangement.The TCT decreased from preoperative (458.69±38.28)μm to (443.86±36.54)μm at 4 months after operation, showing a statistically significant difference ( t=6.705, P<0.001). There was no significant difference in the TCT reduction between groups with and without demarcation lines ( t=1.684, P=0.100). At 4 months postoperatively, the UCVA of all eyes increased from preoperative 0.74±0.37 to 0.69±0.38, and the difference was statistically significant ( t=2.109, P=0.039). There was no significant difference in BCVA between before and after operation ( t=1.006, P=0.319). There was no significant difference in change of UCVA and BCVA between groups with and without demarcation lines ( t=0.065, P=0.949; t=0.346, P=0.730). There was no significant difference in Kmax in all patients between before and after operation ( t=0.050, P=0.950). There was no significant difference in the Kmax change between groups with and without demarcation lines ( t=-0.739, P=0.464). The change in TCT in the epithelium-off treatment group was significantly greater than that in the epithelium-on treatment group ( t=2.815, P=0.008). There was no significant difference in UCVA, BCVA and Kmax changes between epithelium-on and epithelium-off treatment groups (all at P>0.05). There was no obvious corneal scarring, infectious keratitis, corneal endothelial decompensation or other complications. Conclusions:The demarcation line after CXL may be a sign of the depth of cross-linking reaction, which is more prone to occur after the epithelium-off operation method.Both the epithelium-on and epithelium-off operation methods have similar therapeutic effects.Demarcation line after different cross-linking methods has no significant influence on the cross-linking effect in keratoconus.

The stability of cell genetic material is influenced by a variety of factors, both internal and external, which can cause various types of DNA damage, such as DNA alkylation, oxidation, mismatching, loop structure, atypical DNA structure, single-strand break, and double-strand break.These DNA damages disrupt cellular homeostasis and dynamic equilibrium, which cause gene mutations, chromosomal abnormalities, and even degradation, aging, and death at different biological levels.By searching and identifying DNA damage sites, the cell activates a series of biochemical pathways, coordinates the progress of DNA replication and transcription, and then repairs the DNA damage.In this way, the cell maintains its independence and stability.While radiotherapy plays a role in eliminating tumors by DNA damages, it also initiates DNA damage responses.Among the responses, base excision repair, nucleotide excision repair, mismatch repair, double-strand break repair, and post-translesion synthesis repair play a key role in repairing the damages.The dysfunction of these repair pathways will cause differences in tumor radiation sensitivity.This paper summarizes recent research results in DNA damage repair, and focuses on the types of DNA damage and their repair mechanisms, so as to promote the understanding of the great significance of this field and to provide a theoretical basis for exploring the application of DNA damage repair pathways in tumor therapy.

This study was aimed to establish the pharmacokinetics-pharmacodynamics (PK-PD) model of ginsenoside Rb1 following the intravenous administration of Shengmai injection in subjects with stable angina pectoris.A total of stable angina pectoris were selected and received Shengmai injection for 14 days.Plasma samples were collected at different time points.Plasma concentrations of ginsenoside Rb1 were determined by liquid chromatography-mass spectrometry (LC/MS).The concentration-time curves (AUC) were drawn,and then the PK parameters were calculated.The systolic pressure and diastolic pressure were monitored,and the combined PK-PD model was established based on the theory of effect compartment.The results showed that PK of ginsenoside Rb1 conformed to a mono-compartment model.The effect of Shengmai injection lagged behind the concentrations of ginsenoside Rb1 in plasma.The effect exhibited good correlation with ginsenoside Rb1 in effect compartment.The relationship between effect and plasma concentrations fits the Inhibitory Effect Imax model.It was concluded that the study successfully established the combined PK-PD model of ginsenoside Rb1 in subjects with angina pectoris.The model can efficiently evaluate the effective substance of Shengmai injection.

This study was aimed to compare the pharmacokinetics (PK) of Shengmai injection and Shenmai injection with a single injection administration using a constant speed in subjects with stable angina pectoris.A total of 20 subjects with stable angina pectoris were divided into two groups.Each group was administered with Shengmai and Shenmai injection.The liquid chromatography-mass spectrometry (LC/MS) was adopted to determine concentrations of ginsenosides in plasma at different time points.PK parameters were calculated for comparison.The results showed that after a single intravenous infusion of Shengmai and Shenmai injection,the Cm.of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in Shenmai group were higher than those of the Shengmai group with statistical significance (P ≤0.05).There were differences on the T1/2 of ginsenoside Rg1,AUC0-144h and CL of ginsenoside Rc,as well as Tmax of ginsenoside Rd (P ≤ 0.05).However,there was no significant difference shown on other PK parameters.It was concluded that after a single Shengmai or Shenmai injection,there were PK differences of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in the human body.The clinical medication selection should be based on syndrome differentiation and treatment of patients.

OBJECTIVE:To study the pharmacokinetics of the active ingredients of Shenmai injection,including ginsenoside Rg1 and ginsenoside Re,in normal Beagle dogs and those with myocardial ischemia. METHODS:6 Beagle dogs were given isopro-terenol hydrochloride (1.1 mg/kg) sc to establish the model of myocardial ischemia (model group). Another 6 Beagle dogs were given isometric normal saline (2.2 ml/kg) sc as controls group. The two groups of dogs respectively received corresponding drugs sc at 8:00 am and 13:00 pm on day 1 and at 8:00 am on day 2. Each group of dogs were given Shenmai injection(1.6 ml/kg)iv 1 h after administration on day 2,and such intravenous drip lasted for about 1 h. Blood was collected from each group 0,0.25, 0.5,0.75,1(the end of iv),1.5,2,3,4,6,8,12 and 24 h from the start of iv. Liquid chromatography-mass spectrometry was adopted to determine the concentrations of ginsenoside Rg1 and ginsenoside Re in blood,and WinNonlin 6.3 was used to calculate pharmacokinetic parameters for comparison. RESULTS:For ginsenoside Re in the dogs of the model group,t1/2 was(2.69±1.12) h,AUC0-24 h was(2 060.78±812.18)h·μg/L,Vz was(46.16±20.98)ml and CL was(9.02±4.45)ml/h;compared to the normal control group,AUC0-24 h was much greater and Vz and CL were significantly lower,showing a statistically significant difference(P<0.05). No significant difference in the pharmacokinetic parameters of ginsenoside Rg1 was shown between 2 groups(P>0.05). CON-CLUSIONS:Myocardial ischemia may affect the removal of ginsenoside Re in Beagle dogs,but has no effect on the pharmacoki-netic process of ginsenoside Rg1.

Objective To investigate the length of preserved ileocecum in surgical treatment of slow transit constipation ( STC) by sub-total colectomy with antiperistaltic cecorectal anastomosis .Methods A total of 82 patients with STC were divided into two groups according to the random number table method ,with 41 cases in each group ,all the patients of the two groups underwent subtotal colectomy ,intraopera-tive ileocecum was preserved length of group A was 10~15 cm,group B was 2~3 cm.The operation time,intraoperative bleeding volume, postoperative exhaust time and length of hospital stay were compared .Wexner constipation score and gastrointestinal quality of life index ,ab-dominal pain ,frequency score and emptying time of ileocecus before and after 6 months and 12 months between the two groups were com-pared.Results There was no statistically significant difference in the operation time ,intraoperative bleeding volume ,postoperative exhaust time and hospitalization time of two groups (P>0.05).Wexner constipation score,abdominal pain,frequency score of the two groups after 6 months and 12 months decreased significantly (P<0.05,P<0.01),of which the group B was lower than that of the group A (P<0.05,P<0.01). The gastrointestinal quality of life index after operation significantly increased (P<0.01),of which the group B was higher than that of the group A (P<0.01).Ileocecal emptying time of the group B 12 months after operation was shorter than that of the group A (P<0.01),the differences were statistically significant .Conclusion Subtotal colectomy with antiperistaltic cecorectal anastomosis is an effective method to treat STC,which can reduce the length of preserved ileocecum and improve the prognosis of patients .

Objective: To investigate the effect of losartan on angiotensin II (Ang II) expression and myocardial remodeling in myocardial infarction (MI) rats’ model.
Methods: A total of 32 SD male rats were divided into 4 groups, Sham operation group, MI group, MI with losartan 10mg/(kg·d) group and MI with losartan 20mg/(kg·d). n=8 in each group. MI model was established and the electrocardiogram changes before and after MI were recorded, hemodynamic indexes were detected at 4 weeks after MI, pathological changes of myocardial tissue were examined by HE staining. The myocardial mRNA and protein expressions of ACE2 and Ang II were detected by RT-PCR and Western Blot analysis.
Results: Compared with Sham operation group, MI group showed increased LVMI and decreased LVEF P<0.05;the above changes were getting better in both MI with losartan groups in a dose-dependent manner. The pathological examination presented that MI group had myocardial cell swelling, fracture, hyperplasia and inflammatory cell infiltration, those damages were less in MI with losartan groups in a dose-dependent manner, Sham operation group had no pathological changes. Compared with Sham operation group, the mRNA and protein expressions of Ang II were obviously higher in MI group, P<0.05 and the expressions were decreased in MI with losartan groups in a dose-dependent manner;the mRNA and protein expressions of ACE2 were slightly increased in MI group and the expressions were further increased in MI with losartan groups in a dose-dependent manner.
Conclusion: Losartan could increase ACE2 expression and therefore, inhibit Ang II expression and improve the ventricular remodeling in MI rats’ model.

Objective To investigate the feasibility and safety of retroperitoneal laparoendoscopic single-site (LESS) donor nephrectomy using home-made single-port device.Methods From January 2011 to June 2012,11 consecutive LESS left donor nephrectomies using home-made single-port device with conventional laparoscopic instrument were performed through retroperitoneal access in our center.Results The procedures were completed and no complications occurred in all donors.Mean operative time was 149.5 min.Estimated blood loss was 30-350 ml.Warm ischemia time was 2-4 min.The urine output was prompt in all cases.Recipient graft function was normal within 2 weeks.Donor hospital stay was 5-6 days after operation.Conclusion LESS donor nephrectomy using home-made single-port device in our initial experience is feasible and safe.It is also cost-effective and minimally invasive with conventional laparoscopic donor nephrectomy.This technique is a good option for living donor nephrectomy.

Retroperitoneal laparoscopic live donor nephrectomy offers an intrinsic advantage over conventional transperitoneal laparoscopic nephrectomy because of the potentially lower risk for early and late donor intraperitoneal complications. Herein we presented our experience performing retroperitoneal laparoscopic live donor nephrectomy in 105 donors. All donor nephrectomy was successful. There were no donor deaths and no conversion to open surgery. Mean operation time was 112 min (range, 70-200 min). Intraoperative blood loss was 10-150 mL with an average of 30 mL. Warm ischemia time was 1.3 to 6 min with an average of 3.1 min. Postoperative retroperitoneal hematoma occurred in only one case and there were no other surgical complications. Donors were discharged from the hospital 5 to 10 days postoperation. Average postoperative hospital stay was 6.4 days. One graft was removed due to acute rejection. Delayed graft function occurred in two recipients but renal function returned to normal within four weeks. The other recipients had normal renal function in two weeks except three recipients in four weeks. We believe that retroperitoneal laparoscopic live donor nephrectomy is safe, reliable, and less invasive.

Retroperitoneal laparoscopic live donor nephrectomy offers an intrinsic advantage over conventional transperitoneal laparoscopic nephrectomy because of the potentially lower risk for early and late donor intraperitoneal complications.Herein we presented our experience performing retroperitoneal laparoscopic live donor nephrectomy in 105 donors.All donor nephrectomy was successful.There were no donor deaths and no conversion to open surgery.Mean operation time was 112 min (range,70—200 min).Intraoperative blood loss was 10—150 mL with an average of 30 mL.Warm ischemia time was 1.3 to 6 min with an average of 3.1 min.Postoperative retroperitoneal hematoma occurred in only one case and there were no other surgical complications.Donors were discharged from the hospital 5 to 10 days postoperation.Average postoperative hospital stay was 6.4 days.One graft was removed due to acute rejection.Delayed graft function occurred in two recipients but renal function returned to normal within four weeks.The other recipients had normal renal function in two weeks except three recipients in four weeks.We believe that retroperitoneal laparoscopic live donor nephrectomy is safe,reliable,and less invasive.