{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:49:36Z","timestamp":1776840576765,"version":"3.51.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      To evaluate the efficacy of adjunctive\n                      <jats:italic>Mycobacterium vaccae<\/jats:italic>\n                      (\n                      <jats:italic>M. vaccae<\/jats:italic>\n                      ) and vitamin D in patients with initial smear-negative pulmonary tuberculosis (PTB) and to explore their effects on immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective cohort study, 391 patients with initial smear-negative pulmonary tuberculosis were consecutively enrolled and followed for 4\u202fmonths. Patients were assigned to one of three treatment groups: standard anti-tuberculosis therapy (control), standard therapy plus\n                      <jats:italic>M. vaccae<\/jats:italic>\n                      vaccination, and standard therapy combined with\n                      <jats:italic>M. vaccae<\/jats:italic>\n                      and vitamin D. Cytokine levels [interferon-\u03b3 (IFN-\u03b3), interleukin-4 (IL-4), IL-17, IL-10], T cell subset ratios [Th1\/Th2, Th17\/regulatory T cells (Treg)], and clinical outcomes were prospectively assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The combined therapy group showed significant increases in IFN-\u03b3 and Th1\/Th2 ratio, and decreases in IL-4, IL-17, IL-10, and an increase in the Th17\/Treg ratio, indicating a shift toward Th1-dominant immunity. Clinically, lesion absorption (54.33%) and cavity closure (71.13%) rates were highest in the combined group, with a total effective rate of 89.76%, surpassing the control (76.12%) and\n                      <jats:italic>M. vaccae<\/jats:italic>\n                      (79.23%) groups (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt;\u202f0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Adjunctive therapy with\n                      <jats:italic>M. vaccae<\/jats:italic>\n                      and vitamin D enhances immune function and improves clinical outcomes in initial smear-negative PTB, suggesting a synergistic immunotherapeutic effect.\n                    <\/jats:p>\n                  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