OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy （abbreviated as “national centralized procurement policy”） in Guangxi Zhuang Autonomous Region prefecture， and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators （such as availability， affordability， and drug safety） and eighteen third-level indicators （such as completion rate of agreed purchase volume， affordability level， drug revenue proportion） were introduced， guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation （in 2019 and 2020） in terms of differences and change trends. RESULTS In terms of accessibility， the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%， the proportion of diseases involved and median completed procurement rate were 40.16%， and 287.82% respectively， and the total centralized delivery rate was 97.20%. In terms of affordability， the total reduction amplitude in drug price was 74.80% from 2019 to 2022； the charge for medicine per capita in hospitalization， the proportion of medicine used for outpatient service and hospitalization， decreased by 17.61%， 10.22%， and 20.10% in order； the burden levels on medical fares for patients were all below 1 in addition to chronic diseases， and anti-tumor drugs. In terms of the impact on medicine， the ratio of adverse drug reaction event cases in 2022 was 66.00%， an increase of 1.29% compared to the previous； since the implementation of the policy， 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation， and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance， the public medical institutions achieved generic substitution for originator drugs mostly until 2022； about 9.12% of drugs that were non- centrally purchased in the same category were used； 63.39% of people under investigation did not show a need for a second dressing change； drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand， attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic， conducting clinically comprehensive evaluation of selected drugs， and improving reasonable allocation strategy， etc.

Objective To investigate the optimal adaptation period for mice at different developmental stages during metabolic cage experiments, aiming to provide a reference for conducting metabolic research using mice. Methods A total of 80 male C57BL/6J mice at three developmental stages (weaning period M1, adolescent M2, and adulthood M3) were subjected to a 7-day metabolic cage experiment. Data on food intake, water intake, energy expenditure, respiratory quotient, body weight, and activity levels were recorded every five minutes. The collected data were processed using time series decomposition and comprehensive cluster analysis. Statistical differences were compared using repeated measures ANOVA combined with t-test to determine the optimal adaptation period. Results Significant differences in metabolism were observed among mice in different developmental stages (P<0.01). Compared with adolescent (M2) and adult (M3) mice, weaned mice (M1) exhibited lower activity level (P<0.01) and less distinct circadian rhythm. M1 mice had higher oxygen consumption, carbon dioxide production, and energy expenditure, as well as a lower respiratory quotient (all P<0.001), indicating that they mainly relied on fat as an energy source. Analysis of food intake, water intake, and energy expenditure revealed significant differences between the first light cycle (0-12 h) and the second light cycle (24-36 h) across all developmental stages (all P<0.05) . However, there was no significant difference in daily food intake or water intake after 24 hours (both P>0.05). Comprehensive cluster analysis of multiple indicators showed that the overall indicators of mice during the first 24 hours in the metabolic cages did not cluster with those of the subsequent 6 days, demonstrating significant differences. Conclusion Metabolic cage experiment can be used to detect continuous physiological changes in mice. The results suggest that mice can adapt to new metabolic cages environment within 24 hours, providing a theoretical basis for the design of metabolic experiments using mice.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

OBJECTIVE To explore the effect and mechanism of warming channels and activating blood circulation external treat-ment to alleviate peripheral hyperalgesia in knee osteoarthritis(KOA)based on NGF/TrKA signaling pathway.METHODS 30 SD rats were randomly divided into normal group,KOA group and Yiceng group.KOA model was established by anterior cruciate ligament transection(ACLT).14 days after model establishment,rats in Yiceng group were treated with Yiceng patch.The peripheral pain threshold of rats was measured at different time points.The cartilage sections were stained with HE,Aggrecan and type II collagen.The synovial sections were stained with HE,Sirius red,silver and performed with immunostaining.The protein expression of key molecules NGF and TrKA of NGF/TrKA signaling pathway,inflammatory index IL-1β,pain mediator TRPV1,pan-neural mark-ers PGP9.5 and S100 in synovium and complexes transported to dorsal root ganglia(DRG)tissues via nerve endings was determined by Western Blot.The corresponding gene expression was determined by qPCR.The levels of NGF and SP in peripheral blood of rats were determined by ELISA.RESULTS Compared with the KOA group,the cold allodynia and mechanical allodynia thresholds of the rats in the Yiceng group increased(P<0.05,P<0.01);the protein and gene expression of NGF,TrKA,TRPV1,IL-1β,PGP9.5 in the synovial tissue decreased(P<0.05,P<0.01);the protein and gene expression levels of TRPV1,PGP9.5,S100 in the DRG tissue were downregulated(P<0.05,P<0.01).CONCLUSION The warming channels and activating blood circulation external treatment can inhibit the NGF/TrKA signaling pathway,downregulate the gene and protein expressions of NGF,TrKA,TRPV1,IL-1β,PGP9.5,and may inhibit the sprouting of sensory nerve fibers and improve the peripheral hyperalgesia state of rats with KOA.

Based on the view of the correspondence between nature and man in traditional Chinese medicine TCM),TCM master Professor Xia Guicheng attaches importance to the transformation of yin and yang in the female reproductive rhythm and created the"menstrual cycle rhythm regulation method".Women's special physiological phenomena are manifested in the periodic rhythm.The bi-ological clock is the internal mechanism for producing and regulating the physiological behavior and laws of organisms.The biological clock gene is widely expressed in ovarian granulosa cells,theca cells and corpus luteum cells,and is involved in the synthesis of ster-oid hormones,differentiation of follicular somatic cells,follicle development and ovulation and other physiological processes,playing an important role in female reproductive endocrine.Circadian rhythm disorders can lead to reproductive diseases such as menstrual disor-ders,ovarian dysfunction,and endocrine metabolic disorders.There are similarities between TCM time medicine and the biological clock rhythm system.Fully understanding the impact of the biological clock on female ovarian function,revealing its scientific connota-tion,and clarifying the regulatory method and mechanism will have a positive role in resisting reproductive disorders and optimizing fer-tility.

Objective:To evaluate the effect of esketamine on postoperative acute lung injury (ALI) in pediatric patients undergoing living donor liver transplantation.Methods:Sixty pediatric patients of either sex with biliary atresia, aged 0-36 months, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, with cardiac function grade I or Ⅱ, with Child-Pugh grade B or C, undergoing living donor liver transplantation, were divided into 2 groups ( n=30 each) using a computer-generated table of random numbers: control group (group C) and esketamine group (group S). Combined intravenous-inhalational anesthesia was performed with propofol and sevoflurane in both groups, and in addition esketamine was intravenously infused continuously after induction in group S. After anesthesia induction (T 0), at 60 min after start of surgery (T 1), at 10 min after anhepatic phase (T 2), at 60 min after portal vein opening (T 3), and immediately after abdominal closure (T 4), central venous blood samples were collected for determination of the serum concentrations of Clara cell secretory protein 16, surface active protein D, soluble receptor for advanced glycation end-products, high mobility group protein B1, interleukin-1beta and tumor necrosis factor-alpha (using enzyme-linked immunosorbent assay), concentrations of malondialdehyde (using TBA method), and activity of superoxide dismutase (using hydroxylamine method). The dynamic lung compliance was recorded from T 0 to T 4. Blood samples were taken from the radial artery at T 0 and 24 h after surgery (T 5) for blood gas analysis, and oxygenation index and respiratory index were calculated. Lung ultrasound scores were recorded at 24 h before surgery and T 5. The postoperative mechanical ventilation time and duration of intensive care unit stay were recorded. The occurrence of ALI within 7 days after liver transplantation was observed. Results:Compared with group C, the serum concentrations of Clara cell secretory protein 16, surface active protein D, soluble receptor for advanced glycation end products, high mobility group protein B1, interleukin-1beta, tumor necrosis factor-alpha and malondialdehyde were significantly decreased, and the activity of superoxide dismutase was increased at T 3, 4, the oxygenation index was increased and respiratory index was decreased at T 3-T 5, lung ultrasound C score and B score were decreased at T 5, the postoperative mechanical ventilation time and duration of intensive care unit stay were shortened, and the incidence of ALI was decreased in group S ( P<0.05). Conclusions:Esketamine can alleviate postoperative ALI in pediatric patients undergoing living donor liver transplantation.

Objective:To compare the effects of different anesthesia methods on perioperative lung injury in pediatric patients with biliary atresia undergoing living donor liver transplantation.Methods:Ninety-one American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients with biliary atresia, regardless of gender, aged 0-36 months, with cardiac function grade of Ⅰ or Ⅱ and Child-Pugh grade of B or C, undergoing elective living donor liver transplantation, were selected. According to the anesthesia method, the pediatric patients were divided into 3 groups: propofol-based anesthesia group (P group, n=30), sevoflurane-based anesthesia group (S group, n=30) and propofol-sevoflurane-based anesthesia group (PS group, n=31). Group P received intravenous infusion of 1% propofol 9-15 mg·kg -1·h -1. In group S, sevoflurane was inhaled and the end-tidal concentration was maintained at 2.6%-4.0%.In PS group, 1% propofol 9-15 mg·kg -1·h -1 was intravenously infused and sevoflurane was inhaled, maintaining an end-tidal concentration at 1.0%-2.5%. Remifentanil 0.1-1.0 μg·kg -1·min -1 was intravenously infused during operation for analgesia, and cisatracurium besylate 1-2 μg·kg -1·min -1 was intravenously infused to maintain muscle relaxation in three groups. Immediately after anesthesia induction (T 0), at 60 min after start of surgery (T 1), at 10 min of anhepatic phase (T 2), at 60 min after portal vein opening (T 3), and immediately after abdominal closure (T 4), the concentrations of serum Clara cell secretory protein 16 (CC16), surfactant protein (SP-D), soluble receptors for advanced glycation end products (s-RAGE), high mobility group protein B1 (HMGB1), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were measured using enzyme-linked immunosorbent assay method, and lung compliance (Cdyn) was simultaneously recorded. At T 0-T 4 and 24 h after surgery (T 5), the arterial blood gas analysis was performed to calculate the oxygenation index (OI) and respiratory index (RI). Lung ultrasound scores (LUS scores) were assessed at 24 h before surgery and T 5. The occurrence of pulmonary complications was recorded within 7 days after surgery. The survival was observed for 6 months after surgery. Results:There were no statistically significant differences in serum concentrations of CC16, SP-D and s-RAGE concentrations and LUS scores at different time points between group S and group P ( P>0.05). Compared with S group and P group, the serum CC16 concentrations at T 3 and s-RAGE concentrations at T 3, 4 were significantly decreased, and the C and B scores were decreased at T 5 in PS group ( P<0.05). There were no statistically significant differences in the concentrations of serum HMGB1, IL-1β and TNF-α, Cydn and incidence of ALI/ARDS, pulmonary infection, pleural effusion, and atelectasis within 7 days after surgery among the three groups( P>0.05). The 6-month survival rate was 100% in the three groups. Conclusions:Propofol-sevoflurane-based anesthesia has a better efficacy in reducing perioperative lung injury than propofol-based anesthesia and sevoflurane-based anesthesia in the perioperative period of liver transplantation.

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative acute lung injury (ALI) in the pediatric patients undergoing living-related liver transplantation.Methods:Sixty pediatric patients of either sex, aged 4-24 months, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association (NYHA) class Ⅰ or Ⅱ, with Child-Pugh B or C, scheduled to undergo elective left external lobe piggyback living-related liver transplantation, were divided into 2 groups ( n=30 each) using a computer-generated table of random numbers: control group (group C) and TEAS group (group T). In group T, bilateral Zusanli (ST36), Neiguan (PC6), and Feishu (BL13) acupoints were stimulated with disperse-dense waves at the initial intensity of 0.5 mA and frequency of 2/15 Hz, the current intensity was gradually increased until local slight muscle shaking appeared, and continuous stimulation lasted for 30 min at a 30-min interval (a cycle) until the end of operation. TEAS was performed for 30 min at the same time every day up to 1 week after surgery. Stimulus locations in group C were selected at 0.5 cm lateral to the acupoints, and the electrodes with inert medium were attached to the location, with no effective current output from acupuncture treatment instrument. The peak inspiratory pressure, plateau pressure, and pulmonary compliance were recorded before skin incision (T 0), at 30 min after portal vein occlusion (T 1), at 1 h after portal vein opening (T 2), at the end of operation (T 3), and the difference between peak inspiratory pressure and plateau pressure was calculated. Blood samples from the jugular vein were collected at T 0-3 to determine the levels of plasma club cell protein 16 (CC16), surfactant protein D (SP-D), soluble receptor for advanced glycation end products (sRAGE), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) by enzyme-linked immunosorbent assay. Blood samples from the radial artery were collected at T 0-3 for blood gas analysis, PaO 2 and A-aDO 2 were recorded, and oxygenation index (OI) and respiratory index (RI) were calculated. The indwelling time of postoperative tracheal tube and length of ICU stay were also recorded. The lung injury was assessed and scored using ultrasound at 48 h after surgery. The occurrence of ALI within 1 week after operation was also recorded. Results:Compared with baseline at T 0, OI was significantly decreased, RI was increased, and plasma IL-10 concentrations were increased at T 2, 3, and the plasma concentrations of TNF-α, CC16, sRAGE and SP-D were increased at T 1-3 in both groups ( P<0.05). Compared with group C, OI was significantly increased, RI was decreased, the plasma concentrations of sRAGE were decreased, and the plasma concentrations of IL-10 were increased at T 2, 3, and the concentrations of plasma TNF-α, CC16 and SP-D were decreased at T 1-3, the indwelling time of postoperative tracheal tube and length of ICU stay were shortened, the ultrasound score of lung injury was decreased ( P<0.05), and no significant change was found in the incidence of ALI in group T ( P>0.05). Conclusions:TEAS can alleviate ALI in the pediatric patients after living-related liver transplantation.

The ectopic salivary gland refers to the presence of salivary gland tissue in an area other than the site where salivary glands normally exist. They often occur near the line connecting the external ear canal and the medial border of the clavicle. It is extremely rare to occur in the urogenital system. This paper retrospectively analyzed the clinicopathological data of a patient with ectopic salivary glands accidentally discovered due to testicular torsion. Patients are generally asymptomatic. If there is no fistula leading to the skin or mucosal surface, it is difficult to find clinically. The diagnosis depends on postoperative pathological examination. For ectopic salivary glands, surgery is required regardless of the location.