OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

Objective:To evaluate the efficacy and safety of 1 064 nm Nd:YAG picosecond laser of dual-mode with auxiliary functional product introduction in treatment of melasma.Methods:A prospective study was conducted from March 2022 to September 2023 at the Department of Cosmetic Dermatology, Guangzhou Zesee Plastic Surgery Hospital, including 46 female patients with melasma, aged 26-53 (38.5±7.0) years. Patients were randomly divided into two groups using a random number table: experimental group (1 064 nm Nd:YAG picosecond laser dual-mode treatment followed by the introduction of functional product) and control group (1 064 nm Nd:YAG picosecond laser of dual-mode treatment followed by the introduction of 0.9% NaCl), with 23 patients in each group. By using the melasma area and severity index (MASI) score, the physician′s global assessment and the patient′s satisfaction evaluation as evaluation indicators, the treatment effects were assessed at different time points. Adverse reactions were recorded in both groups.Results:At 4 and 12 weeks after the third treatment, the MASI scores in the experimental group were lower than those of the control group ( P<0.001). At 4 weeks after the third treatment, the rate of moderate or above improvement in pigment spots was 95.7% (22/23) in the experimental group, which was higher than the 69.6% (16/23) in the control group ( P=0.011). At 12 weeks after the third treatment, the rate of moderate or above improvement in the experimental group was 30.4% (7/23), which was higher than the 8.7% (2/23) in the control group ( P=0.006). At 24 weeks after the third treatment, the rate of moderate or above improvement in the experimental group was 13.0% (3/23), which was higher than the 0% (0/23) in the control group ( P=0.015). At 4 weeks after the third treatment, the satisfactory rate in the experimental group was 73.9% (17/23), which was higher than the 43.5% (10/23) in the control group ( P=0.009). At 12 weeks after the third treatment, the satisfactory rate in the experimental group was 69.6% (16/23), which was higher than the 39.1% (9/23) in the control group ( P=0.040). At 24 weeks after the third treatment, the satisfactory rate in the experimental group was 56.5% (13/23), which was higher than the 4.4% (1/23) in the control group ( P=0.002). One patient in the experimental group experienced mild itching on the cheek on the second day post-treatment. In the control group, two patients experienced mild itching and erythema on the second day post-treatment. No serious adverse reactions, such as blisters, scabs, or pigmentation, were observed in either group during the treatment or follow-up periods. Conclusion:The 1 064 nm Nd:YAG picosecond laser of dual-mode with auxiliary functional product introduction in treatment of melasma has a better efficacy, with a shorter recovery period and fewer adverse reactions.

Objective:To evaluate the efficacy and safety of 1 064 nm Nd:YAG picosecond laser of dual-mode with auxiliary functional product introduction in treatment of melasma.Methods:A prospective study was conducted from March 2022 to September 2023 at the Department of Cosmetic Dermatology, Guangzhou Zesee Plastic Surgery Hospital, including 46 female patients with melasma, aged 26-53 (38.5±7.0) years. Patients were randomly divided into two groups using a random number table: experimental group (1 064 nm Nd:YAG picosecond laser dual-mode treatment followed by the introduction of functional product) and control group (1 064 nm Nd:YAG picosecond laser of dual-mode treatment followed by the introduction of 0.9% NaCl), with 23 patients in each group. By using the melasma area and severity index (MASI) score, the physician′s global assessment and the patient′s satisfaction evaluation as evaluation indicators, the treatment effects were assessed at different time points. Adverse reactions were recorded in both groups.Results:At 4 and 12 weeks after the third treatment, the MASI scores in the experimental group were lower than those of the control group ( P<0.001). At 4 weeks after the third treatment, the rate of moderate or above improvement in pigment spots was 95.7% (22/23) in the experimental group, which was higher than the 69.6% (16/23) in the control group ( P=0.011). At 12 weeks after the third treatment, the rate of moderate or above improvement in the experimental group was 30.4% (7/23), which was higher than the 8.7% (2/23) in the control group ( P=0.006). At 24 weeks after the third treatment, the rate of moderate or above improvement in the experimental group was 13.0% (3/23), which was higher than the 0% (0/23) in the control group ( P=0.015). At 4 weeks after the third treatment, the satisfactory rate in the experimental group was 73.9% (17/23), which was higher than the 43.5% (10/23) in the control group ( P=0.009). At 12 weeks after the third treatment, the satisfactory rate in the experimental group was 69.6% (16/23), which was higher than the 39.1% (9/23) in the control group ( P=0.040). At 24 weeks after the third treatment, the satisfactory rate in the experimental group was 56.5% (13/23), which was higher than the 4.4% (1/23) in the control group ( P=0.002). One patient in the experimental group experienced mild itching on the cheek on the second day post-treatment. In the control group, two patients experienced mild itching and erythema on the second day post-treatment. No serious adverse reactions, such as blisters, scabs, or pigmentation, were observed in either group during the treatment or follow-up periods. Conclusion:The 1 064 nm Nd:YAG picosecond laser of dual-mode with auxiliary functional product introduction in treatment of melasma has a better efficacy, with a shorter recovery period and fewer adverse reactions.

Background Improper settings of outdoor smoking points in public places may increase the risk of secondhand smoke exposure among the population. Conducting research on air pollution in and around smoking spots and related influencing factors can provide valuable insights for optimizing the setting of outdoor smoking points. Objective To investigate the influence of the number of smokers at outdoor smoking points and the distance on the diffusion characteristics of surrounding air pollutants, in order to optimize the setting of outdoor smoking points. Methods Surrounding the exhibition halls in the China International Import Expo (CIIE), two outdoor smoking points were randomly selected, one on the first floor (ground level) and the other on the second floor (16 m above ground), respectively. At 0, 3, 6, and 9 m from the smoking points in the same direction, validated portable air pollutant monitors were used to measure the real-time fine particulate matter (PM_2.5) and carbon dioxide (CO₂) concentrations for consecutive 5 d during the exhibition, as well as the environmental meteorological factors at 0 m with weather meters including wind speed, wind direction, and air pressure. An open outdoor atmospheric background sampling point was selected on each of the two floors to carry out parallel sampling. Simultaneously, the number of smokers at each smoking point were double recorded per minute. The relationships between the number of smokers, distance from the smoking points, and ambient PM_2.5 and CO₂ concentrations were evaluated by generalized additive regression models for time-series data after adjustment of confounders such as temperature, relative humidity, and wind speed. Results The median numbers of smokers at smoking points on the first and second floors were 6 [interquartile range (IQR): 3, 9] and 9 (IQR: 6, 13), respectively. Windless (wind speed <0.6 m·s⁻¹) occupied most of the time (85.9%) at both locations. The average concentration of ambient PM_2.5 at the smoking points (0 m) [mean ± standard deviation, (106±114) μg·m⁻³] was 4.2 times higher than that of the atmospheric background [(25±7) μg·m⁻³], the PM_2.5 concentration showed a gradient decline with the increase of distance from the smoking points, and the average PM_2.5 concentration at 9 m points [(35±22) μg·m⁻³] was close to the background level (1.4 times higher). The maximum concentration of CO₂ [(628±23) μmol·mol⁻¹] was observed at 0 m, and its average value was 1.3 times higher than that of the atmospheric background [(481±40) μmol·mol⁻¹], and there was no gradient decrease in CO₂ concentration with increasing distance at 0, 3, 6, and 9 m points. The regression analyses showed that, taking smoking point as the reference, every 3 m increase in distance was associated with a decrease of ambient PM_2.5 by 24.6 [95% confidence interval (95%CI): 23.5, 25.8] μg·m⁻³ (23.2%) and CO₂ by 54.1 (95%CI: 53.1, 55.1) μmol·mol⁻¹ (8.6%). Every one extra smoker at the smoking point was associated with an average increase of PM_2.5 and CO₂ by 2.0 (95%CI: 1.7, 2.8) μg·m⁻³ and 1.0 (95%CI: 0.7，1.2) μmol·mol⁻¹, respectively. The sensitivity analysis indicated that, under windless conditions, the concentrations of PM_2.5 and CO₂ at the smoking points were even higher but the decreasing and dispersion characteristics remained consistent. Conclusion Outdoor smoking points could significantly increase the PM_2.5 concentrations in the surrounding air and the risks of secondhand smoke exposure, despite of the noticeable decreasing trend with increasing distance. Considering the inevitable poor dispersion conditions such as windless and light wind, outdoor smoking points are recommended to be set at least 9 m or farther away from non-smoking areas.

ObjectiveTo understand the experience， knowledge and attitudes of e-cigarette users in Shanghai， and to provide evidence for the development of intervention programs for e-cigarette use. MethodsThe Respondent-Driven Sampling （RDS） method was used to recruit 40 e-cigarette users for qualitative interviews from November 2020 to February 2021. NVivo （11.0） software was used to code interview records， and the thematic pattern and relationship analysis were conducted. ResultsIn terms of the reasons and user experience of e-cigarette use， most respondents used e-cigarettes for the first time after recommendation of friends； The reasons for the current use of e-cigarettes focus on the subjective feelings generated by the use of e-cigarettes （easy to use， replacing traditional tobacco， and having many flavors）. Compared with traditional tobacco use， respondents said e-cigarettes tasted good and had no physical impact （they could be used all the time without making them uncomfortable）. In terms of the awareness of e-cigarette use related knowledge， the respondents' opinions on whether e-cigarettes caused health risks were mostly based on their own experience of using them， and they said it was difficult to identify real information online. As for whether they were interested in relevant knowledge， most respondents said they wanted to learn about the professional knowledge related to e-cigarettes. Regarding the attitude related to the use of e-cigarettes， most respondents believed that e-cigarettes are addictive， e-cigarettes are not a safe alternative to traditional tobacco， ande-cigarettes couldn't help them quit smoking. Three out of ten respondents said they supported including e-cigarettes in the Regulation on Smoking Control in Public. ConclusionThere are certain characteristics of e-cigarette users' feelings， related knowledge and attitude towards e-cigarette use that should be targeted to carry out publicity， education and intervention.

Objective: To investigate the effects of denatured collagen type Ⅰ on differentiation of human fibroblasts into myofibroblasts. Methods: A small amount of normal skin donated by burn patients undergoing scar surgery was collected. Human fibroblasts were obtained by method of explant culture and then sub-cultured. The fourth passage of cells were used in the following experiments. (1) Fibroblasts were divided into normal collagen group and denatured collagen group according to the random number table, with 10 wells in each group. Fibroblasts in normal collagen group were cultured on normal collagen type Ⅰ coated coverslips. Fibroblasts in denatured collagen group were cultured on denatured type Ⅰ collagen coated coverslips. Expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemical method, and the percentage of PCNA positive cells was calculated. (2) Another batch of fibroblasts were grouped and treated as in (1), with 12 wells in each group. Proliferation activity of cells was determined with methyl-thiazolyl-tetrazolium colorimetry method. (3) Another batch of fibroblasts were grouped and treated as in (1), and the microfilament morphology of cells was observed by rhodamine-phalloidin staining. (4) Another batch of fibroblasts were grouped and treated as in (1). Expression of α smooth muscle actin (α-SMA) of cells was detected by immunohistochemical method, and expression of OB-cadherin of cells was detected by immunofluorescence method. (5) Another batch of fibroblasts were divided into normal collagen, denatured collagen, and common coverslips groups according to the random number table, with 6 wells in each group. Fibroblasts in normal collagen and denatured collagen groups were treated as in (1), while fibroblasts in common coverslips group were cultured on coverslips without collagen coating. Expressions of α-SMA and OB-cadherin of cells were determined with Western blotting. (6) Another batch of fibroblasts were grouped and treated as in (5), and then the mRNA expressions of collagen type Ⅰ, collagen type Ⅲ, and α-SMA of cells were determined with real-time fluorescent quantitative reverse transcription polymerase chain reaction. Data were processed with t test, one way analysis of variance, and least-significant difference test. Results: (1) The percentage of PCNA positive cells in denatured collagen group was (83±9)%, significantly higher than (29±9)% in normal collagen group (t=13.53, P<0.01). (2) The proliferation activity of fibroblasts in denatured collagen group was 0.32±0.06, significantly higher than 0.25±0.05 in normal collagen group (t=3.06, P<0.01). (3) The microfilament of fibroblasts in normal collagen group was arranged vertically and in parallel way, paralleling the long axis of cells. The microfilament of fibroblasts in denatured collagen group was denser and thicker. (4) Most fibroblasts in normal collagen group showed long shuttle-like shape typically. Morphology of fibroblasts in denatured collagen group changed, and cells were obviously spreading. Expressions of α-SMA and OB-cadherin of fibroblasts in denatured collagen group were stronger than those in normal collagen group. (5) Expressions of α-SMA of fibroblasts in denatured collagen, normal collagen, and common coverslips groups were respectively 1.69±0.41, 0.89±0.27, and 1.46±0.42. Expression of α-SMA of fibroblasts in denatured collagen group was significantly higher than that in normal collagen group (P<0.01). Expressions of OB-cadherin of fibroblasts in denatured collagen, normal collagen, and common coverslips groups were respectively 5.17±0.28, 2.21±0.10, and 4.01±0.56. Expression of OB-cadherin of fibroblasts in denatured group was significantly higher than that in normal collagen group (P<0.01). (6) There was no significant difference in mRNA expression of collagen type Ⅰ of fibroblasts in denatured collagen, normal collagen, and common coverslips groups (F=2.71, P>0.05). The mRNA expressions of collagen type Ⅲ and α-SMA of fibroblasts in normal collagen group were significantly lower than those in denatured collagen group (P<0.01). Conclusions Denatured collagen type Ⅰ may influence the activity of fibroblasts, thus inducing fibroblasts differentiating into myofibroblasts.

Objective To evaluate the diagnostic value of the heparin-binding protein (HBP),procalcitonin (PCT),C-reactive protein (CRP),white blood cell (WBC) in respiratory tract bacterial infection.Methods 66 respiratory tract bacterial infection patients,37 respiratory tract non-bacterial infection patients and 39 control group in the Third Xiangya Hospital from October 2015 to March 2017 was selected as objects in this prospective study.The levels of HBP,PCT and CRP in blood of the objects were tested with ELESA,immunofluorescence assay,immunoturbidimetry respectively;WBC counts were taken by Sysmex XE-5000 blood analyzer.The difference among the three groups was analyzed by Student's t test,one-way ANOVA or Wilcoxon test.Receiver operating characteristic curve was utilized to analyze the diagnostic value of HBP,PCT,CRP and WBC in respiratory tract bacterial infection.Results The plasma level of HBP were 36.30 (7.78-89.36) ng/ml,5.57 (4.37-8.23) ng/ml,2.84 (1.53-6.51) ng/ml in respiratory tract bacterial infection group,respiratory tract non-bacterial infection group and control group respectively.The socre of PCT were 0.08 (0.04-0.83) ng/ml,0.09 (0.04-0.30) ng/ml,0.04 (0.03-0.08) ng/ml.The socre of CRP were 56.20 (19.33-76.23) mg/L,34.40 (2.15-83.95) mg/L,(2.20 ± 0.99) mg/L.The socre of WBC count were (10.59 ±4.58) × 109/L,8.40 (5.80-11.88) × 109/L,(6.14± 1.31) × 109/L.There were statistically significant differences in HBP scores between respiratory tract bacterial infection group and respiratory tract non-bacterial infection group or control group (Z =-4.828,P ＜0.001;Z =-5.685,P ＜ 0.001).There were no statistically significant differences in PCT,CRP and WBC scores between respiratory tract bacterial infection group and non-bacterial infection group (F =0.045,P ＞ 0.05;F =0.100,P ＞ 0.05;F =2.417,P ＞ 0.05),but significant differences between respiratory tract bacterial infection group and control group (Z =-2.881,P ＜ 0.05;Z =-6.595,P ＜ 0.001;t =6.499,P ＜ 0.001).The area under curve (AUC) of HBP,PCT,CRP and WBC diagnosing respiratory tract bacterial infection was 0.89,0.69,0.95 and 0.85 respectively.The AUC of HBP differential diagnosising was 0.80.Conclusion HBP can be used as an efficient supplementary indicator for respiratory tract bacterial infection,the differential diagnostic value is superior to PCT,CRP and WBC.

Objective To observe NLS-KALA-SA-PTX (NKSP) for lung adenocarcinoma cell line A549 in vitro with paclitaxel monotherapy, and the mechanism thereof. Methods MTT assay was used to detect A549 cell proliferation influ-enced by different concentrations of NKSP (20, 40, 80, 100μg/L) and paclitaxel monotherapy (20, 40, 80, 100μg/L) for 24 h, 48 h and 72 h.. Subsequent experiments were divided into four groups, namely, group A (without any drug treatment), group B (added polypeptide 80μg/L of self-assembled nanoparticles, NKS), group C (80μg/L paclitaxel monotherapy) and group D (80μg/L NKSP). Flow cytometry was used to detect the cell apoptotic rates after 48 h and 72 h treatment in four groups. Western blot assay was used to analyse the protein expressions of bax and caspase-3 after 48 h and 72 h treatment in four groups. Results Both paclitaxel monotherapy and NKSP can inhibit the proliferation of A549 cells. The inhibitory rates of paclitaxel monotherapy group at 48 h and 72 h and NKSP group at 72 h showed an increasing trend in a dose-depen-dent manner (P<0.05). After treatment for 48 hours, the apoptotic rate was significantly higher in D group than that of C group (P<0.05). But the apoptotic rate at 72 h was lower in D group than that of C group (P<0.05). The protein expressions of bax and caspase-3 at 48 h were significantl lower in D group than those of C group, which were higher at 72 h in D group than those of C group (P<0.05). Conclusion Compared to paclitaxel monotherapy group, NKS promotes slow release of pa-clitaxol, which reduces the cytotoxicity and extends the antitumor effects.

Objective To investigate the differences of clinical efficacy and untoward reaction of different chemotherapy regi‐mens for patients with malignant glioma on different expression levels of O6‐methylguanine‐DNA‐methyltransferase(MGMT) ,in order to provide references for clinical treatment .Methods Totally 90 cases of patients with malignant glioma in our hospital from January 2011 to January 2013 were selected ,among them ,64 cases of MGMT negative expressing patients were divided into group A and group B with 32 cases in each group ,and 26 cases of MGMT positive expressing patients were enrolled into the group C . Group A was treated with combination of radiotherapy ,teniposide and nimustine ,group B was treated with radiotherapy‐temozolo‐mide combination regimen ,group C was treated with combination of radiotherapy ,teniposide and nimustine .The untoward reactions of the three groups were compared ,and the survival rate was observed after one year follow‐up .Results The hemoglobin ,leuko‐cyte ,granulocyte ,platelet ,bleeding ,alanine aminotransferase ,creatinine ,urea nitrogen ,peripheral neuritis ,untoward reactions a‐mong the three groups had no statistically significant differences (P>0 .05);the incidence rates of nausea and vomiting ,diarrhea , constipation among the three groups had statistically significant differences(P<0 .05) ,in which group C was significantly higher than that of group A and group B(P<0 .05) .Only one case in the group C was lost in the one year follow‐up .The median survival time was 10 months in group A and group B ,and was 7 months in group C .The median survival time in group C was significantly lower when compared with that in group A and group B(χ2 =7 .673 ,P=0 .006 ;χ2 =6 .395 ,P=0 .011) ,while there was no signifi‐cant difference of median survival time between group A and group B(χ2 =0 .063 .P=0 .802) .Conclusion The long‐term prognosis of patients with negative MGMT expression might be significantly worse than that of patients with negative MGMT expression in glioma .

OBJECTIVETo observe the fibrosis of skin after damage to the fat dome structure in skin of pig.

METHODSTotally 4 pieces of skin grafts of intermediate thickness in the size of 5 cm × 5 cm were obtained from both sides beside the spine of back in each of the 4 female red Duroc pigs with pedicle on one side with Humby knife performed by burn specialists, who were rich in clinical experience. These skin grafts were assigned as thin dermis group (TD). Pedicled tissue grafts in the size of 5 cm × 5 cm with the thickness of 1.5 mm were obtained within the wounds resulted from former incision with the same method mentioned above, and these tissue grafts were set as fat dome group (FD). The above-mentioned two groups of skin grafts were sutured back in situ immediately after completion of the former procedures. On post surgery day (PSD) 7, 14, and 21, 5 wounds were respectively selected according to the random number table for gross observation of the surgical areas. Tissue samples were obtained from corresponding surgical area deep to the deep fascia after gross observation at above-mentioned time points. Some of the tissue samples were used for observation of distribution of collagen fibers in the regions of operation of both groups of skin grafts with HE staining, and the breadth of fibrosis was measured; some of the tissue samples were used for observation of distribution of type I or III collagen fibers in the regions of incision of both two groups of skin grafts with Sirius red staining. Data were processed with two independent sample t test.

RESULTSA little scab on the edge of wounds was observed on PSD 7; all the wounds were healed on PSD 14; a few hairs were observed growing in the surgical area on PSD 21. HE staining showed that traces of incision were observed in the superficial layer of dermis and at the junction between dermis and fat dome at each time point; profuse hyperplasia of collagen fibers with parallel and orderly arrangement were observed in the region of incision of skin grafts in groups TD and FD at each time point. The breadth of fibrosis of the region of incision of skin grafts was respectively (251 ± 31), (240 ± 3 7), and (342 ± 69) µm in group TD, (239 ± 36), (286 ± 61), and (332 ± 28) µm in group FD on PSD 7, 14, 21, without significantly statistical difference (with t values respectively 0.750, -1.971, and 0.375, P values above 0.05). Sirius red staining showed that large amount of type III collagen fibers and small amount of type I collagen fibers arranging parallelly were present in the region of incision of skin grafts in groups TD and FD at each time point.

CONCLUSIONSUnder the circumstances of relatively intact restoration of dermal tissue, no excessive fibrosis was observed after simple incisional injury of fat dome in skin of pig.

Animals ; Burns ; surgery ; Dermis ; surgery ; transplantation ; Female ; Fibrosis ; complications ; Graft Survival ; Male ; Skin ; Skin Transplantation ; methods ; Skin, Artificial ; Swine ; Wound Healing