Robotic anatomical resection for hepatocellular carcinoma located within segment 7 using the Glissonean approach.

Worldwide use of robotic-assisted hepatectomy has increased dramatically over the past two decades. The role of robotic liver surgery is still controversial, especially with respect to its long-term oncological outcomes in treating early-stage hepatocellular carcinoma (HCC). The Glissonean approach is a fundamental technique for anatomical resection using open and laparoscopic liver surgery. To our knowledge, there have been few reports on purely robotic anatomical segmentectomy 7 for HCC using the Glissonean approach have been described. The present study describes the technical details and surgical outcomes of totally robotic segmentectomy 7 using the Glissonean approach. Fourteen patients with HCC limited to segment 7 underwent segmentectomy 7 from January 2019 through April 2023 in our hospital. The surgical techniques, peri-operative, and oncological outcomes were analyzed. Purely robotic anatomical segmentectomy 7 using the Glissonean approach was safe and feasible with the technology described herein in all of the 14 patients. The peri-operative and oncological outcomes were better and/or comparable with those of other similar hepatic resections using open approach and/or laparoscopic approach. The median follow-up time was 18 months. Intrahepatic recurrence occurred in 2 (14.3%) patient within one year following surgery. The 3-year overall survival rate was 81%. Although technically challenging, the purely robotic segmentectomy 7 could be performed safely and simultaneously with oncological radicality using the Glissonean approach.

Lattice Strain in High Entropy Oxides Promote CO2 Photomethanation.

Lattice strain is widely investigated to improve the performance of heterogeneous catalysts, however, the effect of lattice strain is under-explored in high-entropy oxide based photocatalyst. In this study, noble-metal-free (CoCrMnFeNi)Ox with lattice strain is synthesized using a temperature-controlled, template-free and salt-assisted strategy. In the presence of lattice strain, an intensive internal electric field is formed in (CoCrMnFeNi)Ox, promoting the separation of photoinduced charge carriers. The size of the (CoCrMnFeNi)Ox can be tuned by varying the calcination temperature. Specifically, (CoCrMnFeNi)Ox prepared at a higher temperature possesses a smaller grain size exposing more active sites, resulting in an enhanced CO2 photomethanation performance. This work provides valuable insights for the rational design of the photocatalysts and highlights the promising role of high-entropy oxides in heterogeneous photocatalysis.

Multifactorial risk prediction analysis of liver metastasis in colorectal cancer: incorporating programmed cell death ligand 1 combined positive score and other factors.

BACKGROUND: The occurrence of liver metastasis significantly affects the prognosis of colorectal cancer (CRC). Existing research indicates that primary tumor location, vascular invasion, lymph node metastasis, and abnormal preoperative tumor markers are risk factors for CRC liver metastasis. Positive expression of programmed cell death ligand 1 (PD-L1) may serve as a favorable prognostic marker for nasopharyngeal and gastric cancers, in which combined positive score (CPS) quantifies the level of PD-L1 expression. This study aimed to explore CPS as a potential risk factor for CRC liver metastasis and integrate other independent risk factors to establish a novel predictive model for CRC liver metastasis. METHODS: A retrospective analysis was conducted on 437 patients with CRC pathologically diagnosed at The Second Xiangya Hospital of Central South University from January 1, 2019, to December 31, 2021. Data were collected, including CPS, age, gender (male and female), primary tumor location, Ki-67 expression, pathologic differentiation, neural invasion, vascular invasion, lymph node metastasis, and preoperative tumor markers. The optimal cutoff point for the continuous variable CPS was determined using the Youden index, and all CPSs were dichotomized into high- and low-risk groups based on this threshold (scores below the threshold were considered high risk, and score above the threshold were considered low risk). Univariate logistic regression analysis was employed to identify risk factors for CRC liver metastasis, followed by multivariate logistic regression analysis to integrate the selected risk factors. The predictive model was validated through the construction of receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A nomogram was constructed for visualization. RESULTS: The determined cutoff point for PD-L1 CPS was 4.5, with scores below this threshold indicating a high risk of CRC liver metastasis. In addition, primary tumor origin other than the rectum, presence of pericolonic lymph node metastasis, and abnormal levels of tumor markers carcinoembryonic antigen and cancer antigen 19-9 were identified as independent risk factors for CRC liver metastasis. The constructed clinical prediction model demonstrated good predictive ability and accuracy, with an area under the ROC curve of 0.871 (95% CI, 0.838-0.904). CONCLUSION: The exploration and validation of CPS as a novel predictor of CRC liver metastasis were performed. Based on these findings, a new clinical prediction model for CRC liver metastasis was developed by integrating other independent risk factors. The DCA, clinical impact curve, and nomogram graph constructed on the basis of this model have significant clinical implications and guide clinical practice.

Unraveling the Enantiomeric Distribution of Glycosidically Bound Linalool in Teas (Camellia sinensis) and Their Acidolysis Characteristics and Pyrolysis Mechanism.

Glycosidically bound linalool plays important roles in the formation of excellent tea flavor, while their enantiomeric distribution in teas and the actual transformations with free linalool are still unclear. In this study, a novel chiral ultrahigh performance liquid chromatography-mass spectrometry/mass spectrometry approach to directly analyze linalyl-ß-primeveroside and linalyl-ß-d-glucopyranoside enantiomers in teas was established and then applied in 30 tea samples. A close transformation relationship existed between the two states of linalool for their consistent dominant configurations (most S-form) and corresponding distribution trend in most teas (r up to 0.81). The acidolysis characterization indicated that free linalool might be slowly released from linalyl-ß-primeveroside with stable enantiomeric ratios during long-term withering of white tea in a weakly acidic environment, along with other isomerized products, e.g., geraniol, nerol, α-terpineol, etc. Furthermore, a novel online thermal desorption-gas chromatography-mass spectrometry approach was established to simulate the pyrolysis releasing of linalyl-ß-primeveroside during tea processing. Interestingly, free linalool was not the selected pyrolysis product of linalyl-ß-primeveroside but rather trans/cis-2,6-dimethyl-2,6-octadiene during the high-fire roasting or baking step of oolong and green teas. The identification of above high-fire chemical marks presented great potential to scientifically evaluate the proper thermal conditions in the practical production of tea.

Investigations of the highly efficient processing technique, chemical constituents, and anti-inflammatory effect of N-ethyl-2-pyrrolidinone-substituted flavan-3-ol (EPSF)-enriched white tea.

N-Ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) are a newly discovered compound class in tea with various bioactivities. This study aimed to develop a novel processing technique to enhance EPSF contents in white tea efficiently. Using optimal processing parameters of 125 °C and 30 min in a high-temperature sterilizing oven, total EPSF content significantly increased by 1.42-18.80-fold to 1.57-6.22 mg/g without impacting sensory characteristics. Metabolomics analysis revealed elevated levels of nucleosides, nucleotides, bases, theaflavins, flavonol aglycones, EPSFs, and most flavone-C-glycosides, as well as decreased levels of amino acids, procyanidins, theasinensins, several flavanols, and flavonol-O-glycosides after EPSF-enrichment treatment. Furthermore, the EPSF-enriched white tea exhibited notable anti-inflammatory effects, mitigating xylene-induced ear edema in mice and carrageenan-induced paw edema and cotton ball-induced granulomas in rats. This study developed a new processing technique for highly efficient enhancement of EPSFs in white tea and demonstrated that EPSF-enriched white tea has a potential to serve as effective anti-inflammatory dietary supplement.

Dynamic Hydroxylation Enhances Hydrogen Atom Abstraction from Water for Nitrogen Fixation Revealed by Isotope Labeling in Situ Fourier-Transform Infrared Spectroscopy.

Employing water as a hydrogen source to participate in the hydrogen atom transfer (HAT) process is a low-cost and carbon-free process demonstrating great economic and environmental potential in catalysis. However, the low efficiency of hydrogen atom abstraction from water leads to slow kinetics of HAT for most hydrogenative reactions. Here, we prepared ultrathin Bi4O5Cl2 nanosheets where the surface can be in situ reconstructed via hydroxylation under light illumination to facilitate the abstraction of hydrogen atoms from pure water for efficient nitrogen fixation. Consequently, the isotope labeling in situ Fourier-transform infrared spectroscopy (FT-IR) involving H2O and D2O has clearly revealed that the hydroxyl groups tend to be adsorbed on the chloride vacancy sites on the Bi4O5Cl2 surface to form hydroxylated surfaces, where the hydroxylated photocatalyst surface enables partial dehydrogenation of water into H2O2, allowing the utilization of H atoms for efficient of N2 hydrogenation via HAT steps. This work elucidates the in-depth reaction mechanism of hydrogen atom extraction from H2O molecules via the light-generated chloride vacancy to promote photocatalytic nitrogen fixation, ultimately enabling the inspiration and providing crucial rules for the design of important functional materials that can efficiently deliver active hydrogen for chemical synthesis.

Comprehensive comparison of aroma profiles and chiral free and glycosidically bound volatiles in Fujian and Yunnan white teas.

The Fujian and Yunnan provinces in China are the most representative origins of white tea. However, the key differences in the chemical constituents of the two white teas have rarely been revealed. In this study, a comprehensive comparison of the aroma profiles, chiral volatiles, and glycosidically bound volatiles (GBVs) in Fujian and Yunnan white teas was performed, and 174 volatiles and 28 enantiomers, including 22 volatiles and six GBVs, were identified. Linalool, linalyl-ß-primeveroside (LinPrim), and α-terpineol presented the opposite dominant configurations in Fujian and Yunnan white teas, and the chiral GBVs were firstly quantified with significant differences in the contents of R-LinPrim and ß-d-glucopyranosides of (2R, 5R)-linalool oxide A and (2R, 5S)-linalool oxide B. Moreover, discrimination functions for Fujian and Yunnan white teas were created using nine key variables with excellent reliability and efficiency. These results provide a new method for objectively distinguishing authentic white teas according to geographical origin.

Stored white tea ameliorates DSS-induced ulcerative colitis in mice by modulating the composition of the gut microbiota and intestinal metabolites.

Changes in the chemical composition of white tea during storage have been studied extensively; however, whether such chemical changes impact the efficacy of white tea in ameliorating colitis remains unclear. In this study, we compared the effects of new (2021 WP) and 10-year-old (2011 WP) white tea on 3% dextrose sodium sulfate (DSS)-induced ulcerative colitis in mice by gavaging mice with the extracts at 200 mg kg-1 day-1. Chemical composition analysis showed that the levels of 50 compounds, such as flavanols, dimeric catechins, and amino acids, were significantly lower in the 2011 WP extract than in the 2021 WP extract, whereas the contents of 21 compounds, such as N-ethyl-2-pyrrolidinone-substituted flavan-3-ols, theobromine, and (-)-epigallocatechin-3-(3''-O-methyl) gallate, were significantly higher. Results of the animal experiments showed that 2011 WP ameliorated the pathological symptoms of colitis, which was superior to the activity of 2021 WP, and this effect was likely enhanced based on the decreasing of the relative abundance of the g_bacteroides and g_Escherichia-Shigella flora in mice with colitis and promoting the conversion of primary bile acids to secondary bile acids in the colon. These results will facilitate the development of novel functional products from white tea.

Re-rolling treatment in the fermentation process improves the taste and liquor color qualities of black tea.

Fermentation is a vital process occurred under the premise of rolling affecting black tea quality. Theoretically, re-rolling during fermentation will remodel the biochemical conditions of tea leaves, and thus influence black tea quality. Herein, we studied the effect of re-rolling on black tea taste and liquor color. Sensory evaluation showed that re-rolling significantly weakened the astringency taste and improved the redness and luminance of liquor. With re-rolling, the color attributes of a* and L* and the contents of theaflavins and thearubigins were significantly improved. Metabolomics analysis showed that the contents of 110 non-volatile compounds were significantly different among black teas with different rolling treatments. In summary, re-rolling accelerated the oxidation of polyphenols into pigments, the hydrolysis of proteins into amino acids, and the metabolism of alkaloids, organic acids, glycosidically-bound volatiles, and lipids during the fermentation period. Our study provided a novel and simple way to improve black tea quality.

Identification of Cu(111) as Superior Active Sites for Electrocatalytic NO Reduction to NH3 with High Single-Pass Conversion Efficiency.

Opting for NO as an N source in electrocatalytic NH3 synthesis presents an intriguing approach to tackle energy and environmental challenges. However, blindly pursuing high NH3 synthesis rates and Faradaic efficiency (FE) while ignoring the NO conversion ratio could result in environmental problems. Herein, Cu nanosheets with exposed (111) surface is fabricated and exhibit a NO-to-NH3 yield rate of 371.89 µmol cm-2 h-1 (flow cell) and the highest FE of 93.19±1.99 % (H-type cell). The NO conversion ratio is increased to the current highest value of 63.74 % combined with the development of the flow cell. Additionally, Crystal Orbital Hamilton Population (COHP) clearly reveals that the "σ-π* acceptance-donation" is the essence of the interaction between the Cu and NO as also supported by operando attenuated total reflection infrared spectroscopy (ATR-IRAS) in observing the key intermediate of NO- . This work not only achieves a milestone NO conversion ratio for electrocatalytic NO-to-NH3 , but also proposes a new descriptor that utilizes orbital hybridization between molecules and metal centers to accurately identify the real active sites of catalysts.

Metabolomics investigation of the chemical variations in white teas with different producing areas and storage durations.

In this study, we employed nontargeted metabolomics and quantitative analysis to explore the variations in metabolites among white teas from different production areas and with varying storage durations. A total of 83 compounds exhibited differential levels between Zhenghe and Fuding white tea, 89 between Zhenghe and Jinggu, and 75 between Fuding and Jinggu white tea. Concerning the storage of white tea, the concentrations of flavanols, dimeric catechins, and amino acids decreased over time, while N-ethyl-2-pyrrolidone-substituted flavanols (EPSFs), caffeine, adenosine monophosphate (AMP), and adenosine increased. Galloylated flavanols showed a higher propensity to form EPSFs with theanine compared to nongalloylated flavanols during storage. Theanine and epigallocatechin gallate were more inclined to generate S-configuration EPSFs during storage in Fuding and Jinggu white tea samples, while R-configuration EPSFs were more readily formed in Zhenghe white tea samples. This study offers a comprehensive understanding of the changes in metabolites during the storage of white tea.

Comprehensive analysis of pigment alterations and associated flavor development in strip and needle green teas.

Strip/needle green teas (SGT/NGT) processed using innovative technologies are in high demand; however, mechanisms behind their color and flavor have not been comprehensively studied. We aimed to reveal the dynamics of major pigmented components (carotenoids, lipids, flavonoids, and Maillard products) and their contributions to the flavor of green teas. The total content of flavonoids in SGT and NGT were 255 ± 4.51 and 201 ± 3.91 mg·g-1, respectively; these values are slightly lower than that in fresh leaves (FLs), resulting in a fresh and sweet aftertaste. In average, carotene content in SGT/NGT (24.8 µg·g-1) was higher than in FL (17.4 µg·g-1), whilst xanthophyll content (603 µg·g-1) decreased to one-half of that in FL (310 µg·g-1). Among the 218 primary metabolites, glutamine, glutamic acid, and arginine were found to accumulate and were dominate contributors for the umami and sweet taste. Notably, more than 96 volatiles were screened and revealed their correlations with carotenoids, lipids, and amino acids. Overall, the synergism between pigments and their non-enzymatic derivates' contribution to GT characterized flavor was illustrated.

Characterization of two O-methyltransferases involved in the biosynthesis of O-methylated catechins in tea plant.

Tea is known for having a high catechin content, with the main component being (-)-epigallocatechin gallate (EGCG), which has significant bioactivities, including potential anti-cancer and anti-inflammatory activity. The poor intestinal stability and permeability of EGCG, however, undermine these health-improving benefits. O-methylated EGCG derivatives, found in a few tea cultivars in low levels, have attracted considerable interest due to their increased bioavailability. Here, we identify two O-methyltransferases from tea plant: CsFAOMT1 that has a specific O-methyltransferase activity on the 3''-position of EGCG to generate EGCG3''Me, and CsFAOMT2 that predominantly catalyzes the formation of EGCG4″Me. In different tea tissues and germplasms, the transcript levels of CsFAOMT1 and CsFAOMT2 are strongly correlated with the amounts of EGCG3''Me and EGCG4''Me, respectively. Furthermore, the crystal structures of CsFAOMT1 and CsFAOMT2 reveal the key residues necessary for 3''- and 4''-O-methylation. These findings may provide guidance for the future development of tea cultivars with high O-methylated catechin content.

Comprehensive metabolic analyses provide new insights into primary and secondary metabolites in different tissues of Jianghua Kucha tea (Camellia sinensis var. assamica cv. Jianghua).

Background: Jianghua Kucha (JHKC) is a special tea germplasm with enriched specialized secondary metabolites, including theacrine, non-epimeric flavanols and methylated flavanols. Moreover, primary metabolites provide precursors and energy for the production of secondary metabolites. However, the accumulation patterns of primary and secondary metabolites in different tissues of JHKC are unclear. Methods: The changes of primary and secondary metabolites and related metabolic pathways (primary and secondary metabolism) in different JHKC tissues (the bud, 1st-4th leaves, and new stem) were investigated via metabolomics analysis with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Results: Significant differences were observed in 68 primary and 51 secondary metabolites mainly related with the pathways of starch and sucrose, amino acids, caffeine, and flavanols metabolism and TCA cycle. The bud exhibited higher levels of glucose-6-phosphate, citric acid, most amino acids, theobromine, catechin-gallate, epicatechin-gallate, procyanidins, and theasinensins; the 1st leaf showed higher levels of caffeine and epigallocatechin-3-gallate; and the 4th leaf contained higher levels of most monosaccharides, theacrine, and epigallocatechin-3-O-(3"-O-methyl)-gallate. In addition, primary metabolites and important secondary metabolites had certain correlations. Conclusion: This study provides comprehensive insight into primary and secondary metabolites in JHKC and offers guidelines for efficiently utilizing specialized metabolites of JHKC in the future.

High-throughput screening and investigation of the inhibitory mechanism of α-glucosidase inhibitors in teas using an affinity selection-mass spectrometry method.

An affinity selection-mass spectrometry method was applied for high-throughput screening of α-glucosidase (AGH) inhibitors from teas. Fourteen out of nineteen screened AGH inhibitor candidates were clustered as galloylated polyphenols (GPs). "AGH-GPs" interaction studies, including enzyme kinetics, fluorescence spectroscopy, circular dichroism, and molecular docking, jointly suggested that GPs noncompetitively inhibit AGH activity by interacting with amino acid residues near the active site of AGH and inducing changes in AGH secondary structure. Representative GPs and white tea extract (WTE) showed comparable AGH inhibition effects in Caco2 cells and postprandial hypoglycemic efficacy in diabetic mice as acarbose. The area under the curve of oral sucrose tolerance test was lower by 8.16%, 6.17%, and 7.37% than control group in 15 mg/kg EGCG, 15 mg/kg strictinin, and 150 mg/kg WTE group, respectively. Our study presents a high-efficiency approach to discover novel AGH inhibitors and elucidates a potential mechanism by which tea decreases diabetes risks.

Nontargeted and targeted metabolomics analysis for evaluating the effect of "golden flora" amount on the sensory quality, metabolites, and the alpha-amylase and lipase inhibitory activities of Fu brick tea.

To investigate the effects of "golden flora" amount on the sensory quality, metabolites and bioactivities of Fu brick tea (FBT), FBT samples with different "golden flora" amounts were prepared from the same materials by adjusting the water content before pressing. With the increase of "golden flora" in samples, the tea liquor color changed from yellow to orange red and the astringent taste gradually diminished. Targeted analysis demonstrated that (-)-epigallocatechin gallate, (-)-epicatechin gallate, and most amino acids gradually decreased as the increase of "golden flora". Seventy differential metabolites were identified by untargeted analysis. Among them, sixteen compounds including two Fuzhuanins and four EPSFs were positively correlated with "golden flora" amount (P < 0.05). The FBT samples with "golden flora" exhibited significantly higher inhibitory potency on α-amylase and lipase than the samples without "golden flora". Our results provide a theoretical basis of guiding FBT processing based on desired sensory quality and metabolites.

Newly found variations of the right posterior portal vein identified radiologically in 1,003 Chinese patients: a cross-sectional study.

Background: The anatomy of the right posterior portal vein (RPPV) plays an important role in planning hepatic resection, living transplantation and interventional radiological procedures, yet the incidence of variations of RPPV without a common trunk in Chinese persons is still unclear. Therefore, we conducted this study and discussed its clinical implications. Methods: A retrospective analysis of multidetector computed tomography (MDCT) scans was performed in 1,933 patients with various abdominal pathologies between September 28, 2018 through May 23, 2019. After excluding 930 patients, a total of 1,003 patients were included in this study. Variations of the RPPV without a common trunk were classified according to classification standards. Results: A total of 1,003 patients were included. RPPV without a common trunk was found in 216 (21.54%, 216/1,003) patients. Among them, we identified three variations of the origin from the right portal vein (RPV): first separate origin of P6, P7, or simultaneous separate origin of P6 and P7, and the incidences of these three variations were 1.50% (15/1,003), 6.58% (66/1,003) and 13.46% (135/1,003), respectively. Among 1,003 patients included in this study, 787 patients (78.46%, 787/1,003) showed that RPPV normally divided into P6 and P7 branches. Conclusions: Variations of the RPPV without a common trunk were not rare in Chinese population. Knowledge of this anatomic variation of the RPPV is extremely important for hepatic and transplant surgeons and interventional radiologists.

Unraveling the electrocatalytic reduction mechanism of enols on copper in aqueous media.

Deoxygenation of aldehydes and their tautomers to alkenes and alkanes has implications in refining biomass-derived fuels for use as transportation fuel. Electrochemical deoxygenation in ambient, aqueous solution is also a potential green synthesis strategy for terminal olefins. In this manuscript, direct electrochemical conversion of vinyl alcohol and acetaldehyde on polycrystalline Cu to ethanol, ethylene and ethane; and propenol and propionaldehyde to propanol, propene and propane is reported. Sensitive detection was achieved using a rotating disk electrode coupled with gas chromatography-mass spectrometry. In-situ attenuated total reflection surface-enhanced infrared absorption spectroscopy, and in-situ Raman spectroscopy confirmed the adsorption of the vinyl alcohol. Calculations using canonical and grand-canonical density functional theory and experimental findings suggest that the rate-determining step for ethylene and ethane formation is an electron transfer step to the adsorbed vinyl alcohol. Finally, we extend our conclusions to the enol reaction from higher-order soluble aldehyde and ketone. The products observed from the reduction reaction also sheds insights into plausible reaction pathways of CO2 to C2 and C3 products.

Metabolomic characterization of the chemical compositions of Dracocephalum rupestre Hance.

Maojian tea (MJT) is a traditional Chinese herbal tea beverage manufactured from the leaves of the Dracocephalum rupestre Hance plant. In this study, a nontargeted metabolomics approach combined with absolute quantifications was applied to comprehensively investigate the chemical compositions of MJT and to determine the effects of the processing methods on compounds. Flavones (apigenin and luteolin, 0.06-1.35 mg/g), flavanones (eriodictyol and naringenin, 0.1-2.3 mg/g), flavone 7-O-glycosides (0.15-5.98 mg/g), flavanone 7-O-glycosides (0.28-19.41 mg/g), and triterpenoids were presumed to be characteristic components of MJT. Applying imitative green and black tea processing methods to MJT led to increases in flavone/flavanone aglycones, lipids, and triterpenoids and decreases in flavone/flavanone glycosides, amino acids, organic acids, and most phenolic acids. This study offers novel insights into the chemical compositions and the influences of processing methods on MJT and will be utilized for the quality control of MJT.

The impact of family doctor system on patients' utilisation of general practitioner in primary care facilities-Evidence from Hangzhou, China.

OBJECTIVE: This study aims to examine whether participating in the contracted family doctor system increases patients' utilisation of primary care general practitioner for multiple disease outcomes in China. METHODS: Binary logistic regression models were estimated using data collected from 372 community residents in nine selected districts of Hangzhou, China. RESULTS: Findings revealed that (1) for patients with influenza, diabetes, upper respiratory infection, and gingivitis, those who participated in the contracted family doctor system were approximately 4.3 times, 98.4%, 92.5%, and 52.8% more likely to choose primary care general practitioners (GP) for their initial diagnosis, respectively, as compared with their counterparts who did not have contracted family doctors; (2) For patients with stroke or cerebrovascular disease and cholecystitis or cholelithiasis, those who had contracted family doctors were 1.111 times and 80.6% more likely to choose primary care GP for their subsequent disease maintenance, respectively, as compared to their counterparts without contracted family doctors. CONCLUSION: Our findings indicate that the contracted family doctor system not only increases the utilisation of primary care GP for patients with many chronic conditions but also promotes the overall completion of China's hierarchical medical system in the long run. Policy implications were provided to help policymakers actively construct and develop the contracted family doctor system to promote the hierarchical medical system in China.