Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Objective To evaluate the patient-reported outcome(PRO)of patients with breast cancer who underwent autologous breast reconstruction and implant breast reconstruction.Methods Patients who underwent breast reconstruction in Shanghai Cancer Center,Fudan University from Jan 2020 to Jun 2021 were selected,including 111 patients who underwent autologous breast reconstruction and 108 patients who underwent implant breast reconstruction.Chinese version Breast-Q2.0 scale,breast cancer specificity scale QLQ-BR23 and EORTC quality of life scale QLQ-C30 were used to investigate the PRO of the two groups 18 months after operation.Results The rate of stage Ⅲ breast cancer in the self-weight construction group was higher than that in the implant reconstruction group(64.9%vs.44.4%,P<0.001).The preoperative neoadjuvant therapy and postoperative radiotherapy in the autologous reconstruction group were higher than those in the implant reconstruction group(P<0.001).Postoperative chemotherapy and endocrine therapy in the autologous reconstruction group were lower than those in the implant reconstruction group(P<0.001).The study based on Breast-Q scale showed that the breast satisfaction of autologous reconstruction group was higher than that of implant reconstruction(59.28±17.20 vs.54.94±14.48,P<0.05).The study based on QLQ-BR23 showed that the self-weight construction group was higher than the implant reconstruction group in the field of arm symptoms(20.02±20.80 vs.12.65±16.18,P<0.05).The study based on QLQ-C30 scale showed that there was no significant difference in all functional areas and symptom areas of patients.There was no significant difference in the number and time of social regression between the two groups.Conclusion Breast reconstruction can improve the PRO of breast cancer patients,and oncology factors will affect the choice of breast reconstruction.Patients with autologous breast reconstruction are more satisfied with breast appearance,but upper limb symptoms such as swelling and pain are more obvious than implant reconstruction,which is related to the higher proportion of axillary lymph node dissection in patients with autologous reconstruction.There is no significant difference in quality of life and social regression between the two groups.

Objective: To explore the feasibility of moving epidemic method (MEM) in the assessment of seasonal influenza (influenza) activity intensity from the perspective of urban agglomeration, assess influenza activity intensity in the Beijing-Tianjin-Hebei region from 2019 to 2021 and evaluate the reliability of surveillance data and the effectiveness of the MEM model application. Methods: The weekly reported incidence rate (IR) of influenza and the percentage of influenza-like illness (ILI%) from 2011-2021 in Beijing-Tianjin-Hebei region were collected to establish MEM models respectively. The model fitting effect and the reliability of the two data were evaluated for the purpose of establishing an optimal model to assess the influenza activity intensity in Beijing-Tianjin-Hebei region from 2019-2021. A cross-validation procedure was used to evaluate the performance of the models by calculating the Youden's index, sensitivity and specificity. Results: The MEM model fitted with weekly ILI% had a higher Youden's index compared with the model fitted with weekly IR at both Beijing-Tianjin-Hebei region level and provincial level. The MEM model based on ILI% showed that the epidemic threshold in Beijing-Tianjin-Hebei region during 2019-2020 was 4.42%, the post-epidemic threshold was 4.66%, with medium, high and very high intensity thresholds as 5.38%, 7.22% and 7.84%, respectively. The influenza season during 2019-2020 had 10 weeks (week 50 of 2019 to week 7 of 2020). The influenza season started in week 50 of 2019, and the intensity fluctuated above and below medium epidemic level for six consecutive weeks. The high intensity was observed in week 4 of 2020, the threshold of very high intensity was excessed in week 5, and the intensity gradually declined and became lower than the threshold at the end of the influenza season in week 8. The epidemic threshold was 4.29% and the post-epidemic threshold was 4.35% during 2020-2021. Influenza activity level never excessed the epidemic threshold throughout the year, and no epidemic period emerged. Conclusions: The MEM model could be applied in the assessment of influenza activity intensity in Beijing-Tianjin-Hebei region, and the use of ILI% to assess influenza activity intensity in this region was more reliable than IR data. Influenza activity intensity in Beijing-Tianjin-Hebei region was higher during 2019-2020 but significantly lower in 2020-2021.
Humans ; Beijing/epidemiology* ; Influenza, Human/epidemiology* ; Seasons ; Reproducibility of Results ; Epidemics ; China/epidemiology*

This paper introduced the overview of the "eight trends" of Chinese medicinal materials(CMM) industry in 2021, analyzed the problems of CMM production, and put forward development suggestions. Specifically, "eight trends" could be summarized as follows.(1) The growing area of CMM tended to be stable, and some provinces began to release the local catalog of Dao-di herbs.(2) The protection process of new varieties accelerated, and a number of excellent varieties were bred.(3) The theory of ecological cultivation was further enriched, and the demonstration effect of ecological cultivation technology was prominent.(4) Some CMM realized complete mechanization and formed typical model cases.(5) The number of cultivation bases using the traceability platform increased, and provincial internet trading platforms were set up.(6) The construction of CMM industrial clusters accelerated, and the number of provincial-level regional brands increased rapidly.(7) Many new agricultural business entities were founded nationwide, and a variety of methods were used to drive the intensified development of CMM.(8) A number of local TCM laws were promulgated, and the management regulation of food and medicine homology substances catalogs was issued. On this basis, four suggestions for CMM production were proposed.(1) It is suggested to speed up the formulation of the national catalog of Dao-di herbs and carry out the certification of Dao-di herbs production bases.(2) Ecological planting of forest and grassland medicine should be further strengthened in terms of technical research and promotion based on the principle of ecological priority.(3) The basic work of disaster prevention should be paid more attention and technical measures for disaster mitigation should be developed.(4) The planted area of commonly used CMM should be incorporated into the national regular statistical system.
Agriculture ; Certification ; Commerce ; Industry ; China

OBJECTIVES: To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). METHODS: A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. RESULTS: Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). CONCLUSIONS Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.
Child ; Humans ; Valproic Acid/therapeutic use* ; HMGB1 Protein ; Pilot Projects ; Tumor Necrosis Factor-alpha ; Neuroinflammatory Diseases ; NLR Family, Pyrin Domain-Containing 3 Protein ; Prospective Studies ; Brain Injuries, Traumatic/pathology*

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli