In this paper， by referring to ancient and modern literature， the textual research of Kochiae Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， taste and efficacy， harvesting time， processing and compatibility taboo， so as to provide reference and basis for the development and utilization of related famous classical formulas. According to the investigation， it can be seen that Difuzi was first published in Sheng Nong's Herbal Classic， and has been used as the official name throughout history. It is also known by other names such as Dimai， Dikui， and Luozhou. The mainstream source of Difuzi in materia medica throughout history is the dried ripe fruit of Kochia scoparia， which is consistent throughout history. In the Han dynasty， it was recorded that Kochiae Fructus was produced in Jingzhou（Hubei province）， while modern literature records its distribution throughout the country， so it does not have obvious geoherbalism. The harvesting period of Kochiae Fructus is mostly in the late autumn， and the quality is best when it is full， gray green in color， and no impurities. There are two processing methods for its origin：from the Southern and Northern dynasties to the Ming dynasty， it was dried in the shade， and after the founding of the People's Republic of China， it was dried in the sun. There are few records about the processing of Kochiae Fructus， and its clinical application is mostly based on raw products as medicine. The seedlings are harvested in February of the lunar calendar， and the leaves are taken in April and May， processing in the place of origin is shade drying， the processing methods include burning ash and frying frost， pounding juice and wine soaking. For internal use， it is mostly decocted or mashed， while for external use， it is mostly washed with decoction or taken in a soup bath. Throughout history， it has been recorded that Kochiae Fructus is bitter and cold， and is mainly used for treating bladder fever. After the founding of the People's Republic of China， most of the literature classified it as damp-clearing medicine. Since the 1985 edition of Chinese Pharmacopoeia， it has been recorded that Kochiae Fructus has a pungent and bitter taste， and a cold nature. Returning to the kidney and bladder meridians with functions of clearing heat and dampness， dispelling wind and relieving itching. The clinical contraindications are mainly prohibited for those with deficiency and no dampness and heat. Throughout history， it has been recorded that the taste of the seedlings and leaves is bitter and cold for treatment of dysentery. Since modern times， it has been used to regulate the liver， spleen and large intestine meridians， with functions such as clearing heat and detoxifying， and diuresis. Based on the textual research， it is recommended to use the dried ripe fruit of K. scoparia when developing the famous classical formulas containing Kochiae Fructus， and processing shall be carried out according to the original processing requirements. If the original formula does not specify the processing requirements， the raw products is taken into medicine.

In this paper， by referring to ancient and modern literature， the textual research of Cnidii Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， nature and flavour， efficacy， harvesting and processing， compatibility taboo and others， so as to provide reference and basis for the development and utilization of the relevant famous classical formulas. After textual research， it can be verified that Cnidii Fructus was first published in Sheng Nong's Herbal Classic， the materia medica of all dynasties was named Shechuangzi， and there are also aliases such as Shesu， Shemi， and Qiangmi. The main source for generations was the dried ripe fruit of Cnidium monnieri， and ancient and modern consistent. From the Eastern Han dynasty to Tang dynasty， the origin of Cnidii Fructus was Zibo， Shandong province. During the Five dynasties， it expanded to Yangzhou in Jiangsu province and Xiangyang in Hubei province， the Song dynasty added Shangqiu in Henan province， and it was considered that Yangzhou， Xiangyang and Shangqiu were its genuine producing areas. It was more widely distributed in Ming and Qing dynasties. After the founding of the People's Republic of China， the origin is clearly distributed throughout the country. For its quality evaluation， generally full grain， gray yellow color， strong aroma is the best. The harvesting period in the past dynasties was mostly the fifth lunar month， and the fruit was collected to remove impurities and dry. The mainstream processing in producing area of the past dynasties was net selection of raw products， mixing and steaming with the juice of Rehmanniae Radix and stir-frying were the mainstream processing methods in the past， there were also stir-frying with honey， stir-frying with salt and rice wine， immersing and steaming with rice wine and other methods. In recent times， it has been used in raw products as medicine. Sheng Nong's Herbal Classic recorded Cnidii Fructus was bitter， Supplementary Records of Famous Physicians recorded its acrid for the first time. It was recorded in the Ming dynasty that its nature was warm， acted on the kidney meridian， and had small toxicity. After the founding of the People's Republic of China， most of the literature classified it as a medicine to attack poison， kill insects and relieve itching with the functions of dispelling pathogenic wind and removing dampness， destroying parasites and elieving itching， warming kidney and activating Yang. Clinical contraindications are mainly contraindicated for people with damp-heat from the lower-jiao or kidney heat. Based on the textual research， it is suggested that when developing the famous classical formulas containing Cnidii Fructus， the source shall be the dried ripe fruit of C. monnieri， and then it shall be processed according to the original formulas. If there is no requirement for processing in the formulas， the raw products can be taken into medicine.

ObjectiveTo evaluate the clinical efficacy and safety of Huaban Jiedu Formulation （化斑解毒方， HJF） in treating psoriasis vulgaris with blood-heat syndrome. MethodsA randomized， double-blind， placebo-controlled study was conducted with 60 patients diagnosed with psoriasis vulgaris of blood-heat syndrome. Patients were randomly assigned to either a treatment group or a control group， with 30 cases in each. The treatment group received HJF granules orally， one dose a day， combined with topical Qingshi Zhiyang Ointment （青石止痒软膏）， while the control group received placebo granules， one dose a day， combined with the same topical ointment. Both groups were topically treated twice daily of 28 days treatment cours. Psoriasis area and severity index （PASI）， visual analogue scale for pruritus （VAS）， traditional Chinese medicine （TCM） syndrome scores， dermatology life quality index （DLQI）， and psoriasis life stress inventory （PLSI） were assessed before treatment and on day 14 and day 28. Response rates for PASI 50 （≥50% reduction） and PASI 75 （≥75% reduction）， as well as overall clinical efficacy， were compared between groups. Serum levels of interleukin-6 （IL-6） and interleukin-17 （IL-17） were measured before and after 28 days of treatment. Adverse reactions during treatment were recorded. ResultsAfter 28 days of treatment， both groups showed significant reductions in PASI total score， lesion area score， erythema， scaling， and infiltration scores， pruritus VAS score， TCM syndrome score， DLQI， PLSI， and serum IL-6 and IL-17 levels （P＜0.05）. Compared to the control group， the treatment group had significantly greater improvements in PASI total score and erythema score， TCM syndrome score， serum IL-6 and IL-17 levels， and PASI 50 response rate after 28 days （P＜0.05）. Between-group comparisons of score differences before and after 28-day treatment revealed that the treatment group showed significantly better improvements in PASI total， lesion area score， erythema score， TCM syndrome score， DLQI， PLSI， and inflammatory markers （P＜0.05 or P＜0.01）. The total effective rate on day 14 and day 28 was 40.00% （12/30） and 83.33% （25/30） in the treatment group， versus 6.90% （2/29） and 41.38% （12/29） in the control group， respectively. The clinical efficacy in the treatment group was significantly superior to that in the control group （P＜0.05）. Mild gastric discomfort occurred in 3 patients in the treatment group and 1 in the control group. ConclusionHJF can effectively improve skin lesions and TCM symptoms relieve pruritus， enhance quality of life， and reduce inflammatory markers IL-6 and IL-17， in patients with blood-heat syndrome of psoriasis vulgaris， with a good safety profile.

Sophorae Flavescentis Radix is one of the commonly used traditional Chinese medicine in China, and a large amount of pharmaceutical residue generated during its processing and production is discarded as waste, which not only wastes resources but also pollutes the environment. Therefore, elucidating the chemical composition of the residue of Sophorae Flavescentis Radix and the differences between the residue and Sophorae Flavescentis Radix itself is of great significance for the comprehensive utilization of the residue. This study, based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology combined with multivariate statistical methods, provides a thorough characterization, identification, and differential analysis of the overall components of Sophorae Flavescentis Radix and its residue. Firstly, 61 compounds in Sophorae Flavescentis Radix were rapidly identified based on their precise molecular weight, fragment ions, and compound abundance, using a self-constructed compound database. Among them, 41 compounds were found in the residue, mainly alkaloids and flavonoids. Secondly, through principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA), 15 key compounds differentiating Sophorae Flavescentis Radix from its residue were identified. These included highly polar alkaloids, such as oxymatrine and oxysophocarpine, which showed significantly reduced content in the residue, and less polar flavonoids, such as kurarinone and kuraridin, which were more abundant in the residue. In summary, this paper clarifies the overall composition, structure, and content differences between Sophorae Flavescentis Radix and its residue, suggesting that the residue of Sophorae Flavescentis Radix can be used as a raw material for the extraction of its high-activity components, with promising potential for development and application in cosmetics and daily care. This research provides a scientific basis for the future comprehensive utilization of Sophorae Flavescentis Radix and its residue.
Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Mass Spectrometry/methods* ; Sophora/chemistry* ; Flavonoids/chemistry* ; Alkaloids/chemistry*

PURPOSE: To investigate the regulatory role of nerve injury-induced protein 1 (NINJ1) in the anti-inflammatory function of human umbilical cord mesenchymal stem cells (hUC-MSCs) co-stimulated by interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). METHODS: hUC-MSCs were expanded in vitro using standard protocols, with stem cell characteristics confirmed by flow cytometry and multilineage differentiation assays. The immunomodulatory properties and cellular activity of cytokine-co-pretreated hUC-MSCs were systematically evaluated via quantitative reverse transcription RT-qPCR, lymphocyte proliferation suppression assays, and Cell Counting Kit-8 viability tests. Transcriptome sequencing, Western blotting and small interfering RNA interference were integrated to analyze the regulatory mechanisms of NINJ1 expression. Functional roles of NINJ1 in pretreated hUC-MSCs were elucidated through gene silencing combined with lactate dehydrogenase release assays, Annexin V/Propidium Iodide apoptosis analysis, macrophage co-culture models, and cytokine Enzyme-Linked Immunosorbent Assay. Therapeutic efficacy was validated in a cecal ligation and puncture-induced septic mouse model: 80 mice were randomly allocated into 4 experimental groups (n=20/group): sham group (laparotomy without cecal ligation); phosphate-buffered saline-treated group (cecal ligation and puncture (CLP) + 0.1 mL phosphate-buffered saline); hUC-MSCs (small interfering RNA (siRNA)-interferon-gamma and tumor necrosis factor-alpha co-stimulation (IT))-treated group (CLP + hUC-MSCs transfected with scrambled siRNA); and hUC-MSCs (siNINJ1-IT)-treated group (CLP + hUC-MSCs with NINJ1-targeting siRNA). RESULTS: hUC-MSCs demonstrated compliance with International Society for Cellular Therapy criteria, confirming their stem cell identity. IFN-γ/TNF-α co-pretreatment enhanced the immunosuppressive capacity of hUC-MSCs, accompanied by the reduction of cellular viability, while concurrently upregulating pro-inflammatory cytokines such as interleukin-6 and interleukin-1β. This co-stimulation significantly elevated NINJ1 expression in hUC-MSCs, whereas genetic silencing of NINJ1 effectively suppressed pro-inflammatory cytokine production and attenuated damage-associated molecular patterns release through inhibition of programmed plasma membrane rupture. Furthermore, the NINJ1 interference potentiated the ability of cytokine-pretreated hUC-MSCs to suppress LPS-induced pro-inflammatory responses in RAW264.7 macrophages. In cecal ligation and puncture-induced sepsis model, NINJ1-silenced hUC-MSCs exhibited enhanced therapeutic efficacy, manifested by reduced systemic inflammation and multi-organ damage. CONCLUSION Our findings shed new light on the immunomodulatory functions of cytokine-primed MSCs, offering groundbreaking insights for developing MSC-based therapies against inflammatory diseases via interfering the expression of NINJ1.
Mesenchymal Stem Cells/drug effects* ; Animals ; Interferon-gamma/pharmacology* ; Tumor Necrosis Factor-alpha/pharmacology* ; Humans ; Mice ; Umbilical Cord/cytology* ; Cells, Cultured ; Apoptosis ; Male

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

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: Bacteroides, as one of the most abundant and diverse genera in the human gut, is regarded as a window into the study of gut microbiota-host interactions. Currently, CRISPR/Cas-based gene editing systems targeting Bacteroides have been widely applied, while the large size of Cas nucleases limits their potential application scenarios (such as in situ gut Bacteroides editing based on phage delivery). Therefore, this study aims to develop a compact and highly efficient genetic editing tool in Bacteroides., We developed a miniaturized CRISPR/Cas gene editing system for human gut Bacteroides. First, the editing capabilities of different miniaturized CRISPR/Cas systems, including AsCas12f, CasΦ2, and ISDge10, were evaluated in Bacteroides fragilis. Subsequently, the editing capability of AsCas12f was assessed across various Bacteroides species, and the size of this system was further optimized. The results demonstrated that the CRISPR/AsCas12f genome editing system exhibited the highest editing efficiency in B. fragilis. The CRISPR/AsCas12f system achieved efficient genome editing in B. fragilis, Bacteroides thetaiotaomicron, and Phocaeicola vulgatus. Furthermore, with a repair template of 500 bp homologous arms, the editing efficiency remained as high as 94.7%. In conclusion, CRISPR/AsCas12f can serve as a chassis tool enzyme for the development of Bacteroides-based miniature gene editors and derivative technologies, laying a foundation for the further development of gene editing technology for Bacteroides.
CRISPR-Cas Systems/genetics* ; Gene Editing/methods* ; Bacteroides/genetics* ; Humans ; Gastrointestinal Microbiome/genetics* ; Bacteroides fragilis/genetics*