ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Objective To determine the difference in blood microcirculation recovery between normal frostbite and high-altitude frostbite during the wound healing.Methods Twenty four male rats were randomly divided into control group (n=8), normal frostbite group (n=8), and high-altitude group (n=8). The normal frostbite group rats were frozen to produce mid-degree frostbite models by controlling the freezing time with liquid nitrogen penetration equipment. The high-altitude frostbite group rats were acclimated to a hypoxic and low-pressure environment for 1 week, and then the high-altitude frostbite models were constructed by the same way with liquid nitrogen penetration apparatus. On days 3, 7, 11, 15, 19, and 23 after modeling, the recovery situation of blood circulation of each group was observed with contrast ultrasonography by injecting SonoVue micro-bubble into rats' tail. Finally, the micro-bubble concentration (MC) was calculated to confirm the blood circulation recovery with software Image Pro. ResultsAt different time points, the wound area of the high-altitude frostbite group was bigger than that of the normal frostbite group, and the MC of control group was always about (27±0.2)×109/ml. On day 3, 7, 11, 15, 19, and 23, the MC was significantly lower in the high-altitude frostbite group than in the control group and normal frostbite group (P<0.05). The MC of normal frostbite group was significantly lower than that of the control group on day 3, 7, 11, 15 and 19 (P<0.05). In addition, no obvious difference in MC was found between normal group and control group on the 23th day (P<0.05).Conclusion The blood microcirculation recovery after high-altitude frostbite is significantly slower than the normal frostbite.

Objective To determine the effects of non-thermal biological effect of low frequency pulsed electromagnetic field (LFPEF) with 15 Hz and 30 mT on ulcer wound during the plateau stress ulcer cure.Methods Thirty male Sprague-Dawley rats were assigned to three equal groups:control,normal cure group (NC) and exposure treatment groups (ET).The plateau rats stress ulcer models were constructed with the combination method of a hypoxic and low-pressure acclimation and the stimulation of absolute ethyl alcohol irrigating stomach.The LFPEF equipment generated the LFPEF of 15 Hz,40％ duty cycle and 30 mT to expose and treat the rats' stomach of ET group with the frequency of 3 hours each day.After 6 days of exposure treatment,the stress ulcer cure situation of each group was evaluated by the methods of macroscopic observation,the gastric juice pH values detection and ulcer index (UI) measurement.Results After 6 days of model,the macroscopic observation showed that the ulcer of NC group was worse than the that of ET group (P＜0.05).The pH values and UI of ET group were significantly different with those of NC group,and closed to those of the control group.Conclusion The nonthermal biological effect of LFPEF could promote the plateau stress ulcer cure.

BACKGROUND:Epidermal stem cels are the source of cels for repairing the skin and its appendages. To study differentiation and migration of epidermal stem cels is crucial for perfect healing.
Objective: To investigate the effects of substance P in skin wound repair.
METHODS:Thirty Wistar rats were randomized into groups of substance P, capsaicin and control (n=10 per group). After the establishment of skin defect models, exogenous neuropeptide substance P, capsaicin, and normal saline were daily injected at the wound for continuous 5 days. Skin thickness, skin wound area, BrdU-positive cels were detected in the three groups at different time after injection.
Results and conclusions:No difference n the skin thickness was found in the three groups at 14 days after injection (P > 0.05), but with time, the epidermal thickness was reduced. At 42 days, the epidermal thickness was reduced remarkably in the substance P group and decreased certainly in the capsaicin group, but unchanged in the control group. The wound area of the substance P group was significantly lower than that in the control and capsaicin groups at 3, 5, 7 days after injection (P < 0.05), but there was no difference between the control and capsaicin group (P > 0.05). The BrdU positive rates in the three groups were significantly different at 3, 5, 7, 12 days after injection: the substance P group > the control group > the capsaicin group (P < 0.05). These results show that substance P can promote epidermal cel proliferation and accelerate wound healing.

BACKGROUND:There is no clear understanding on the effects of subcutaneous fat and stem cels on wound healing. OBJECTIVE:To explore the therapeutic effects of skin composite prepared with adipose tissue-derived stem
cels on skin defects. METHODS: Epidermal cels, fibroblasts, adipose tissue-derived stem cels as seed cels and bovine colagen gel as a scaffold were used to build a complex with a variety of cels. A 6-mm diameter circular skin defect was made on the both sides of the rat back. The right side as experimental side was implanted with an 8-mm diameter multilayer skin composite, and the left side (control side) was only treated with a simple dressing. RESULTS AND CONCLUSION: For the constructed multi-layer skin composite, the epidermal layer was continuously merged into the multi-layer, the fibroblasts evenly distributed in the corium layer, and lipid droplets existed in the fat layer in which the cels distributed uniformly. Cel aggregation was obviously observed at the junction of different layers. In the experimental side, the rate of wound healing, granulation tissue thickness, the thickness of dermis and the capilary density were significantly higher than those in the control side. Taken together, we can construct multilayer skin composites with a variety of cels as seed cels, such as epidermal cels, fibroblasts and adipose tissue-derived stem cels, and bovine colagen gel as a scaffold, which promote wound healing and increase the thickness of dermis.