ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

OBJECTIVE To establish refined medication rules for parenteral nutrition （PN） and evaluate its effectiveness. METHODS Refined medication rules for PN were constructed based on drug instructions， relevant guidelines， and expert consensus. Through the pre-approval review system of prescription automatic screening system （PASS）， PN prescription information for inpatients from January to December 2024 （referred to as “post-intervention”） was collected to analyze the post- intervention prescription review status. PN prescription information for inpatients at our hospital from January to December 2023 and January to December 2024 was collected through the medical order review system to evaluate the rationality rates of PN prescriptions. RESULTS The established refined medication rules for PN included system module rules （including nutrients， drug compatibility， PN concentration and osmotic pressure） and custom review rules （covering off-label drug use， drug compatibility， and other drug use conditions）. As of December 2024， the PASS pre-approval review system had established a total of 102 rules， comprising 55 system module rules and 47 custom review rules for PN. After intervention， when comparing with the first quarter of 2024， the number of PN reviewed and intervened by pharmacists decreased， the pharmacist intervention rate dropped， while the rate of physician modifications following pharmacist intervention increased in the fourth quarter. The primary types of irrational prescriptions identified by the system module rules were irrational PN concentration and osmotic pressure. The primary types of irrational prescriptions identified by the custom review rules were off-label drug use （specifically indications for amino acids） and irrational drug incompatibility. In 2024， the number of false-positive tasks and the false-positive rate initially increased and then decreased， while both the number of irrational prescriptions identified through manual review and the false-negative rate showed a declining trend. In 2024， the overall rationality rate after manual review PN refined medication rules for PN medical order review system significantly increased compared to that in 2023 （P＜0.01）. CONCLUSIONS The refined medication rules for PN in our hospital were established successfully， which can reduce the PN-induced risks and significantly improve the rationality of PN prescriptions.

ObjectiveTo investigate the therapeutic effect of Dayuanyin on acute lung injury induced by H1N1 infection and decipher the potential mechanism. MethodThe constituents in Dayuanyin were analyzed by ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry （UHPLC-Q-Exactive Orbitrap MS）. Forty-eight female BALB/c mice were randomized into normal， model， oseltamivir （19.5 mg·kg^-1）， and low-， medium-， and high-dose （2.73， 5.46， 10.92 g·kg^-1） Dayuanyin groups. The normal and model groups were administrated with deionized water by gavage， and the other groups were administrated with the corresponding drugs by gavage. On day 3 of drug administration， the normal group received nasal inhalation of normal saline， and the other groups were inoculated intranasally with A/RP/8/34 （H1N1） for the modeling of influenza virus infection. Mice were administrated with drugs continuously for 7 days and weighed daily. Sampling was performed 12 h after the last administration， and the lung tissue was weighed to calculate the lung index. Hematoxylin-eosin staining was performed to observe the pathological and morphological changes of the lung tissue and bronchi. The cytometric bead array （CBA） was used to measure the serum levels of interferon-gamma （IFN-γ）， C-X-C motif ligand 1 （CXCL1）， tumor necrosis factor-alpha （TNF-α）， chemokine ligand 2 （CCL2）， interleukin-12p70 （IL-12p70）， chemokine ligand 5 （CCL5）， interleukin-1β （IL-1β）， chemokine （C-X-C motif） ligand 10 （CXCL10）， granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin-10 （IL-10）， interferon-beta （IFN-β）， interferon-alpha （IFN-α）， and interleukin-6 （IL-6）. According to the results of mass spectrometry and network pharmacology， we analyzed the mechanism of Dayuanyin in treating acute lung injury caused by H1N1. The protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， nuclear factor-kappa B （NF-κB）， and their phosphorylated forms were determined by Western blot. The mRNA levels of myeloid differentiation factor 88 （MyD88）， Toll-like receptor 3 （TLR3）， Toll-like receptor 7 （TLR7）， and Toll-like receptor 8 （TLR8） in the lung tissue were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultA total of 57 compounds， including paeoniflorin and baicalein， were detected in Dayuanyin. Compared with the normal group， the model group showed decreased body weight （P<0.01）， lung edema and hemorrhage， increased lung index （P<0.01）， and elevated levels of IFN-γ， IL-12p70， CCL5， IL-1β， CXCL10， GM-CSF， IFN-β， and IL-6 （P<0.01）. Compared with the model group， Dayuanyin attenuated alveolar wall thickening， capillary congestion， and immune cell infiltration， reduced the alterations in body weight and lung index （P<0.01）， and down-regulated the protein levels of IFN-γ， IL-12p70， CCL5， IL-1β， CXCL10， GM-CSF， IFN-β， and IL-6 （P<0.01）. A total of 57 key genes were predicted by network pharmacological analysis， of which the MAPK signaling pathway was the main target signaling pathway. Compared with the normal group， the model group showed up-regulation in the protein levels of phosphorylation （p）-ERK1/2， p-p38 MAPK， and p-NF-κB （P<0.01） and the mRNA levels of TLR7， TLR8， MyD88， and TLR3 （P<0.05， P<0.01）. Compared with the model group， Dayuanyin lowered the phosphorylation levels of ERK1/2， p38 MAPK， and NF-κB p65 in a dose-dependent manner （P<0.01） and down-regulated the mRNA levels of TLR3， TLR7， TLR8， and MyD88 （P<0.01）. ConclusionDayuanyin can prevent and control H1N1 infection-induced acute lung injury by inhibiting the TLR/MAPK/NF-κB signaling pathway.

Objective:To investigate the effect of staged operations with oral mucosa preimplantation urethral plate in the treatment of crippled hypospadias.Methods:The clinical records of patients with crippled hypospadias which were treated in the First People’s Hospital of Zunyi from March 2019 to March 2023 were retrospectively reviewed. Staged operations with oral mucosa preimplantation urethral plate were applied to all patients. The survival condition of preimplantation urethral plate, urethrocutaneous fistula, urethral dehiscence, urethral diverticulum, urethrostenosis, residual chordee, the appearance of penis and urinating condition were observed.Results:Twelve male children were enrolled, ranging in age from 5 years and 1 month to 14 years, with a median age of 8 years and 2 months. All of these patients had 2 to 4 times of urethroplasty surgeries with an average time of 3.2. All patients suffered from moderate to severe chordee and lack of prepuce, including 5 patients with urethral dehiscence, 3 cases with multiple urethrocutaneous fistulas and 4 cases with urethrostenosis. All patients were followed 6 to 36 months after surgery with an average of 25 months. One patient suffered from infection of preimplantation urethral plate after the first stage operation was cured by hyperbaric oxygen therapy and local dressing. Two patients complained of urethrocutaneous fistula after the second stage operation were cured by fistulectomy. No urethral dehiscence, urethral diverticulum, urethrostenosis or residual chordee was observed in other patients. Penile appearance was not bloated and the longitudinal slit urethral orifice was located in the head of the penis. Urination was smooth and the urine line was continuous.Conclusion:Staged operation with oral mucosa preimplantation urethral plate is an effective and safe method for the treatment of crippled hypospadias.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective:To investigate the effect of staged operations with oral mucosa preimplantation urethral plate in the treatment of crippled hypospadias.Methods:The clinical records of patients with crippled hypospadias which were treated in the First People’s Hospital of Zunyi from March 2019 to March 2023 were retrospectively reviewed. Staged operations with oral mucosa preimplantation urethral plate were applied to all patients. The survival condition of preimplantation urethral plate, urethrocutaneous fistula, urethral dehiscence, urethral diverticulum, urethrostenosis, residual chordee, the appearance of penis and urinating condition were observed.Results:Twelve male children were enrolled, ranging in age from 5 years and 1 month to 14 years, with a median age of 8 years and 2 months. All of these patients had 2 to 4 times of urethroplasty surgeries with an average time of 3.2. All patients suffered from moderate to severe chordee and lack of prepuce, including 5 patients with urethral dehiscence, 3 cases with multiple urethrocutaneous fistulas and 4 cases with urethrostenosis. All patients were followed 6 to 36 months after surgery with an average of 25 months. One patient suffered from infection of preimplantation urethral plate after the first stage operation was cured by hyperbaric oxygen therapy and local dressing. Two patients complained of urethrocutaneous fistula after the second stage operation were cured by fistulectomy. No urethral dehiscence, urethral diverticulum, urethrostenosis or residual chordee was observed in other patients. Penile appearance was not bloated and the longitudinal slit urethral orifice was located in the head of the penis. Urination was smooth and the urine line was continuous.Conclusion:Staged operation with oral mucosa preimplantation urethral plate is an effective and safe method for the treatment of crippled hypospadias.

Objective To analyze the epidemiological characteristics of imported cases with Plasmodium ovale infections in Jiangsu Province from 2012 to 2020, so as to provide insights into the development of the imported malaria control strategy in the province. Methods All data pertaining to cases with definitive diagnosis of P. ovale malaria in Jiangsu Province from 2012 to 2020 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China, including the date of going abroad and returning to China, time of malaria infections overseas, date of malaria onset, initial diagnosis and definitive diagnosis. All data pertaining to epidemic status were descriptively analyzed. Results A total of 347 cases of P. ovale malaria were reported in Jiangsu Province from 2012 to 2020, with the highest number seen in 2015 (71 cases). All cases were laboratory-confirmed overseas imported malaria cases, accounting for 14.32% of all reported malaria cases in Jiangsu Province during the period from 2012 to 2020. The 5 cities with the highest number of imported P. ovale malaria cases included Lianyungang City (53 cases, 15.27%), Nantong City (44 cases, 12.68%), Huai’an (44 cases, 12.68%), Taizhou City (44 cases, 12.68%) and Yangzhou City (36 cases, 10.37%). The highest number of imported P. ovale malaria cases was reported in October (39 cases, 11.24%), and the lowest number was seen in December (21 cases, 6.05%). P. ovale infections mainly occurred in were Equatorial Guinea (97 cases, 37.95%), Angola (60 cases, 17.29%) and Nigeria (40 cases, 11.53%). The median duration between returning to China and malaria onset was 64 (144) days, and 7.49% (26/347) of all cases developed malaria one year after returning to China. The initial diagnosis of P. ovale malaria was mainly made at county-level medical institutions (117 cases, 33.72%), and the definitive diagnosis was mainly made at city-level medical institutions (122 cases, 35.16%). The correct rate of initial diagnosis of P. ovale malaria increased from 0 in 2012 to 78.26% in 2020, appearing a tendency towards a rise year by year (χ² = 50.90, P < 0.01). Conclusions Imported P. ovale malaria cases were reported in Jiangsu Province each year from 2012 to 2020, and P. ovale infections predominantly occurred in Africa. Initial and definitive diagnoses of P. ovale malaria were mainly made at city- and county-level medical institutions. Training on the detection ability of malaria parasites is recommended among grassroots microscopists to improve the diagnostic ability of P. ovale malaria, and consolidate the achievements of malaria elimination in Jiangsu Province.

OBJECTIVE To improve the a pplicability of the prescription pre-review system to traditional Chinese medicine （TCM），and improve the quality of prescription review and rational drug use. METHODS The inappropriate pre-review rules of TCM prescription in prescription automatic screening system of our hospital were summarizd ，review rules were revised and the review process was standardized purposefully. The data of prescription review of Chinese patent medicine and TCM decoction pieces were collected from outpatient and emergency department of our hospital in the second quarter of 2020 （before the optimization of review rules ）and the fourth quarter of 2021（after the optimization of review rules ）. The reasonable rate of prescription and effective rate of intervention before and after the optimization of review rules were compared，and unreasonable problems were counted. RESULTS In our hospital ，the pre-review system had poor applicability in reviewing TCM prescriptions. There were some problems ，such as inconsistent or nonstandard names of TCM decoction pieces ，unreasonable dosage range settings，mechanical review of repeated drug use ，excessively strict review of “eighteen incompatible medicaments ”and“nineteen medicaments of mutual restraint ”and lack of safety warnings for special populations. In view of the above problems ，our hospital standardized the name of TCM decoction pieces ，and optimized the review rules such as dose range of TCM decoction pieces ， usage and dosage of Chinese patent medicine ，repeated medication ，drug interaction ，drug taboos for special people ，etc. After the revision of the rules ，the qualification rate of Chinese patent medicine prescriptions increased from 97.38％ to 98.17％（P＞0.05）， and the rate of effective intervention increased from 42.86％ to 79.71％（P＜0.05）；the qualification rate of TCM decoction pieces prescriptions increased from 47.98％ to 79.29％（P＜0.05），and the rate of effective intervention increased from 11.17％ to 29.13％（P＜0.05）. The number of unreasonable problems such as excessive daily dosage of TCM ，excessive dosage range ，drug interaction and drug contraindications for special groups decreased significantly in our hospital （P＜0.05）. There was no statistical significance in the number of unreasonable problems of repeated medication between 2 groups （P＞0.05），but there was a downward trend. T he total number of unreasonable problems had also decreased significantly （P＜0.05）. CONCLUSIONS The optimization measures of review rules in our hospital canimprove the applicability of the review system for TCM prescriptions，and improve the quality of prescription review and the level of rational drug use. However ，review rules of indications and the effectiveness of prescription intervention still needs to be further improved.

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
Androgen Antagonists/adverse effects* ; Exanthema/chemically induced* ; Far East ; Humans ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Thiohydantoins/adverse effects*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*