Existing nucleos（t）ide analogues and pegylated interferon exhibit limited efficacy in the functional cure of hepatitis B. Recently， small nucleic acid drugs， such as antisense oligonucleotides and small interfering RNAs， have brought unprecedented breakthroughs in the functional cure of hepatitis B with their brand-new mechanisms of action and remarkable efficacy in early clinical studies. Small nucleic acid drugs， such as antisense oligonucleotides and small interfering RNAs， can reduce the level of HBsAg and strive to achieve HBsAg seroclearance. The reduction in HBsAg may restore the hepatitis B-specific immune function of the body to some extent and may further transform the simple clearance of HBsAg into hard endpoints with clinical value， such as reducing hepatitis B-related liver events. By meticulously analyzing the dynamic trajectory of HBsAg alterations within the context of new drug applications and further optimizing combined treatment strategies and regimens， it is expected to transform the functional cure of hepatitis B into the ultimate goal of improving survival rates and quality of life.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

OBJECTIVE To provide a reference for the adjustment of antibacterial drug regimens， identification of adverse reactions， and personalized pharmaceutical care for patients with bullous pemphigoid and pulmonary aspergillosis combined with disseminated Nocardia farcinica infection. METHODS Clinical pharmacists participated in the entire treatment process of a patient with bullous pemphigoid and pulmonary aspergillosis combined with disseminated N. farcinica infection. Evidence-based medicine was used to assist in the selection of an initial combined drug regimen against nocardiosis， and timely communication with the microbiology laboratory to provide early antimicrobial susceptibility data. When the patient exhibited epilepsy， the suspected drugs were identified， and it was reminded that imipenem-cilastatin sodium could affect the efficacy of valproic acid. It was suggested to replace valproic acid with levetiracetam for anti-epileptic treatment and to discontinue imipenem-cilastatin sodium. During treatment， it was recommended to monitor the blood concentrations of voriconazole and linezolid， and assist in adjusting the dosage promptly based on the monitoring results. RESULTS The physicians accepted the recommendations of the clinical pharmacists. The patient’s condition improved， and they were discharged with medication. CONCLUSIONS Based on evidence-based medical evidence， antimicrobial susceptibility test results， and blood concentration monitoring data， clinical pharmacists assist clinicians in selecting a sensitive anti-infective regimen for the patient， identifying adverse reactions， adjusting the treatment regimen and providing full-course medication monitoring to ensure the safety and efficacy of clinical drug therapy.

The seco-prezizaane-type sesquiterpenes (SPS), as a special class of sesquiterpenes with a highly oxidative five-ring cage structure and seven consecutive chiral centers, are isolated from the genus Illicium, which have a variety of biological activities, including neurotoxicity and neurotrophic effects, etc. This review summarizes the chemical constituents and pharmacological effects of SPS, and discusses the potential trend and scope of future research.

Objective To explore the changes of serum thyroid peroxidase antibody (TPOAb), thyroglobulin (Tg), and anti-thyroglobulin antibody (Tg-Ab) in patients with gestational thyroid dysfunction and their relationship with pregnancy outcomes. Methods The clinical data were collected from 98 patients with gestational thyroid dysfunction in Nanchong Mental and Physical Hospital between January 2020 and December 2022. According to disease types, patients were divided into hyperthyroidism group (n=50) and hypothyroidism group (n=48). A total of 100 pregnant women with normal thyroid function during the same period were enrolled as the healthy group. The levels of serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroid hormone (FT4), TPOAb, Tg and Tg-Ab, and maternal and neonatal outcomes were compared among the three groups. According to maternal and neonatal outcomes, patients with gestational thyroid dysfunction were divided into normal pregnancy group (n=68) and adverse pregnancy group (n=30), and levels of serum TPOAb, Tg and Tg-Ab were compared between the two groups. Results Compared with the healthy group, level of serum TSH was decreased in the hyperthyroidism group (P<0.05), while levels of serum FT3, FT4, Tg, Tg-Ab and TPOAb were increased (P<0.05). Compared with the healthy group, levels of serum FT3 and FT4 were decreased in the hypothyroidism group (P<0.05), while levels of serum TSH, TPOAb, Tg and Tg-Ab were increased (P<0.05). The level of serum TSH in the hyperthyroidism group was lower than that in the hypothyroidism group (P<0.05), while levels of serum FT3, FT4, Tg, Tg-Ab and TPOAb were higher than those in the hypothyroidism group (P<0.05). There was no significant difference in the overall incidence of adverse pregnancy outcomes between the hyperthyroidism group and the hypothyroidism group (34.00% vs 27.08%, P>0.05), but the overall adverse pregnancy outcome rate in the two groups was higher than that in the healthy group (9.00%, P<0.05). The levels of serum TSH, TPOAb and Tg-Ab in adverse pregnancy group were higher than those in normal pregnancy group (P<0.05). Conclusion The levels of serum TPOAb, Tg and Tg-Ab are abnormally increased in patients with gestational thyroid dysfunction, which are all related to adverse pregnancy outcomes. Clinical attention should be paid to and early intervention should be taken.

ObjectiveTo investigate the possible mechanism of Quyu Jiedu Formula （祛瘀解毒方） in the treatment of endometriosis in terms of iron autophagy mediated by nuclear receptor coactivator 4/nuclear factor κB （NCOA4/NF-κB） signalling pathway. MethodsFifty female SD rats were randomly divided into sham surgery group， model group， mifepristone group， low- and high-dose Quyu Jiedu Formula group， with 10 rats in each group. In the sham surgery group， only operation of opening and closing abdomen was performed， and in the remaining groups， the rat with endometriosis was modelled by autotransplantation. On the next day after successful modelling， saline 2 ml/d was given by gavage to the sham surgery group and the model group； mifepristone 1.05 mg/（kg·d） was given by gavage to the mifepristone group； Quyu Jiedu Formula 12.23 g/（kg·d） and 48.92 g/（kg·d） were given to the low- and high-dosage Quyu Jiedu Formula groups， respectively administered for 4 weeks consecutively. In the remaining 4 groups， all ectopic endometrial tissues were removed from the rats. The volume of ectopic lesions was measured in the model group， the mifepristone group， and the low- and high-dose Quyu Jiedu Formula groups， and the pathological changes of endometrial/ectopic tissues were observed by HE staining， and the protein expression and expression of NCOA4， Ferritin Heavy Chain 1 （FTH1）， Panax quinquefolium （P62）， Microtubule-associated Protein 1 Light Chain 3β （LC3B）， and P-NF-κB protein expression and NCOA4， FTH1， LC3B， P62 mRNA expression were detected in the endometrium and ectopic tissues； the co-localisation of NCOA4 and LC3B， free iron content， and levels of interleukin 6 （IL-6） and tumour necrosis factor α （TNF-α） in endometrial/eutopic endometrial tissues were also detected. ResultsNo ectopic lesions were seen in the sham surgery group. The ectopic tissues of rats in the model group showed obvious pathological damage， while the pathological damage of the ectopic tissues of rats in each admi-nistration group was reduced to different degrees. Compared with the model group， the volume of ectopic lesions was reduced in the mifepristone group and the high- and low-dose Quyu Jiedu Formula groups， and the volume of ectopic lesions in the high-dose Quyu Jiedu Formula group and the mifepristone group was significantly smaller than that in the low-dose Quyu Jiedu Formula group （P＜0.01）. Compared with the sham surgery group， the ectopic tissues of the model group showed up-regulation of LC3BⅡ/LC3B I values， NCOA4， and P-NF-κB protein expression， down-regulation of P62 and FTH1 protein expression， increase in free iron content and IL-6 and TNF-α levels， and increase in the co-localisation positivity rate and co-localised cell density of NCOA4 and LC3B （P＜0.05 or P＜0.01）. Compared with the model group， the ectopic endothelial tissue LC3BⅡ/LC3BⅠ values and the expression of NCOA4 and P-NF-κB proteins were down-regulated in the low- and high-dose Quyu Jiedu Formula group and mifepristone group， the colocalisation positivity rate of NCOA4 and LC3B significantly reduced， and the content of free iron and the level of IL-6 decreased （P＜0.05 or P＜0.01）. Compared with the mifepristone group， P62 more obvious up-regulated and TNF-α level reduced in the high-dose Quyu Jiedu Formula group （P＜0.05）. Compared with the low-dose Quyu Jiedu Formula group， the free iron content of ectopic tissues and the levels of IL-6 and TNF-α reduced in the high-dose Quyu Jiedu Formula group （P＜0.01）. ConclusionThe mechanism of endometriosis treatment by Quyu Jiedu Formula may be related to the inhibition of iron autophagy mediated by the NCOA4/NF-κB signalling pathway in endometriotic tissues， which improves endometrial inflammation.